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598 Cards in this Set
- Front
- Back
- 3rd side (hint)
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What are the 3 layers of cell development in the embryonic disc |
Ectoderm Mesoderm Endoderm |
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What is the formulation of our nervous system called? |
Gastrulation |
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The 6 basic processes of neurodevelopment |
Cell birth/proliferation Cell migration Cell differentiation and maturation Synaptogenesis Cell death and synaptic pruning Myelination (myelogenesis |
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2 ways cells migrate |
Chemical signals Physical support provided by radial glia |
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2 types of dendritic developments |
Dendritic arborisation (branching) Growth of dendritic spines (little swellings of the dendrite on the neuron) |
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Whats the growing end of the axon called |
A growth cone |
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What are the extentions called that a growth cone makes in order to make contact with another cell |
Filopodia |
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What 2 molecules are secreted from target sites to attract growth cones |
Cell adhesion molecules (CAM) Topic Molecules (attract or repel growth cones) |
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What is "successful neural connections survive and others die" called |
Neural Darwinism |
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2 Neurotrophic Factors |
Nerve Growth Factor Brain Derived Neurotrophic Factor |
Proteins NGF BDNF |
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Word for programmed cell death |
Apoptosis |
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Other type of cell death to apoptosis |
Necrosis |
(damaging, from brain damage/too much excitability) |
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For immature neurons to avoid apoptosis and survive it needs: |
Neurotrophins Communications with other neurons (strengthen synapses - Hebb) |
2 things |
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What is dendritic branch changes related to |
Learning or experience |
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What produces myelin |
Glia |
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How quick is the process of myelination |
Slow - gradual for decades |
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What glia produces myelination in the CNS? |
Oligodendroglia |
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What glia produces myelination in PNS |
Schwann cells |
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What stage of development does the brain begin to develop |
Embryonic |
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What is spina bifida |
Failure of the closure of the neural fold at the level of the spinal cord |
Type of neural tube deficit that entails... |
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What prevents spina bifida |
Folic acid |
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What is anencephaly |
Brain fails to develop |
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Alcohol enhances which process of cell neurodevelopment |
Apoptosis |
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What is potential |
Where male and female anatomy is the same during prenatal development |
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What are the female ducts called |
Müllerian |
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What are the male ducts called? |
Wolffian |
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What causes the development of the Wolffian ducts to develop into seminal vesicles and vas deferens? |
Testosterone |
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What causes degeneration of the Müllarian ducts? |
Müllerian Inhibiting hormone |
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What do males have more of instead of estrogen (opposite to females) |
Androgen |
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3 brain sex differences |
Males have more dendriric branching in the visual cortex. Females have more dendritic branching in the motor cortex. Part of corpus callosum bit thicker in females than males. |
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3 stages of prenatal development |
Germinal stage Embryonic stage Fetal stage |
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When is neurogenesis mostly completed? |
7 months of gestation |
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Where was new neuronotenesis postnatally first discoverer |
In songbirds |
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What 2 parts of the adult brain shows neurogenesis |
Olfactory bulb Hippocampus |
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Does the cerebral cortex show neurogenesis in adults? |
Not generally Exceptions following injury or stroke |
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The recovery of damaged axons involves what |
Collateral sprouting |
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What is collateral sprouting |
Non-damaged axons attaching to vacant spots left from damaged axons |
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Evidence of "use it or lose it" principle |
Hebb - rats kept in home (richer enviroment) faster to solve maze than those in lab |
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How does enriched environments affect rats brains? |
Increases dendritic branching (correlated with improved ability to learn) |
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MRI scans reveal what 3 things in musicians? |
Temporal lobe in right hemisphere is 30% larger. Thicker grey matter responsible for hand control and vision. Larger than normal area of the postcentral gyrus in the right hemisphere for movement of left hand. |
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3 broad waves for critical period in order (younger - older) |
Senses Language Higher cognition |
Richard Tees - train ride |
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Blakemore and coopers critical period example |
Kitten verticle lines no horizontal |
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What are the 3 parts of Truine Brain - Mc Leans |
Neomammalian Paleomammalian (limbic system) Reptilian |
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How does the Truine Brain explain the romanian orphans developmental delays and attachment problems |
In neglect, neomammalian brain underdeveloped, less able to control reptillian brain. In stress/trauma, overdeveloped midbrain/reptillian brain. = more impulsivity, substance abuse, emotional problems, violence |
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Explanation for why adolescents are more impulsive |
Prefrontal cortex is immature (decision making) Nucleus accumbens (midbrain) well-developed (pleasure and pain) |
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What test shoes adolescent impulsivity? |
Anti-saccade task (look away from powerful attention getter) |
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How does the grey matter in childhood change gradually |
Thickens in childhood, thins out gradually after |
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Why does the grey matter change in adolescents? |
Synaptic pruning Increase in white matter (myelination) Use it or lose it |
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What are the 4 nucleotide bases? |
Adenine (A) Thymine (T) Cytosine (C) Gyanine (G) |
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What does DNA stand for |
Deoxyribonucleic acid |
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What are the 2 base pairs |
Adenine - Thymine Guyanine - Cytosine |
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What turns on genes? |
Transcription factors |
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What is transcription |
In the nucleus, the gene's dna sequence is copied into messenger RNA (mRNA) |
For gene expression |
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What is gene translation? |
A ribosome attaches to the mRNA and moves along it, reading each triplet codon (3 bases) and using transfer RNAs (tRNA) to put together the amino acid chain to make a protein. |
In gene expression |
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What does mitosis make |
Somatic cells (daughter cells identical to parents) |
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What does meiosis make |
Gametes (daughter cells contain half number of chromosomes) |
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What is the 'crossing over' between nonsister chromatids called? |
Homologous recombination |
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What inheritance is Mendel's law |
Mendalian |
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What is Mendelain inheritance |
Inheritance through 'transmissible units' Law of segregation of genes Law of independent assortments (copies) Law of dominance (over recessive) |
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What did peas show for Mendel's law |
Tall peas = dominant Dwarf peas = recessive TT + dd = 4 × Td Td + Td = TT, Td, Td, dd |
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What is it called if genes are identical? |
Homozygous |
TT or dd |
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What is it called if genes are not identical? |
Heterozygous |
Td |
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What is the name an example of human dominant inheritance |
Huntington's Chorea |
HC |
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What does Huntington's Chorea lead to |
Progressive deterioration of movement, temperament and cognition |
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If a parent has huntingtons, what % of the offspring will develop Huntington |
50% |
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What is the cause of Huntington's |
Single gene disorder on chromosome 4 Due to excessive repeat of CAG biases |
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Name of an example of recessive inheritance |
Phenylketonuria (PKU) |
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What is phenylketonuria? |
Build up of phenylalanine toxic to developing brain: Learning difficulties Behavioural difficulties Epilepsy |
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If both parents are carriers of phenylketonuria, what % of offspring will have the disease |
25% |
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If both parents have phenylketonuria, what % of offspring will be carriers? |
50% |
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What causes phenylketonuria? |
Mutation in the PAH gene - enzyme that breaks down dietary phenylalanine |
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How can phenylketonuria (PKU) be prevented |
Diet control |
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What is monosomy |
Single copy of a chromosome |
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What is trisomy? |
Three copies of a chromosome |
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In downs syndrome, there is a trisomy in which chromosome? |
21 |
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What are the characteristics of Downs syndrome |
Small brain size Facial features Poor muscle tone Heart condition Early onset Alzheimer's disease |
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How do our bodies deal with ensuring cells function normally with either one or 2 X chromosomes |
Random X inactivation early in development |
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The process of X-inactivation can be shown where |
Cats |
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What is an X linked disorder almost exclusively affecting females |
Rett syndrome |
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What does Rett syndrome lead to |
Profound mental impairment |
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What does Rett syndrome do |
Mutation in the gene MeCP2 - a transcription repressor turning off expression of unwanted genes |
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Why is Rett syndrome specific to females |
Not all cells express mutated MePC2 gene so milder symptoms |
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What is an X-linked disorder mostly associated with males |
Fragile X |
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Why is fragile X symptoms predominantly in males |
Milder penetrance in females due to X-inactivation so not always recognised |
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What are alleles |
Variants of a gene |
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What are epigenetics? |
Changing how DNA are expressed based on things binding to or changing how the DNA sequence is transcribed, blocking access to genes or making genes more accessible |
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In epigenetics, does the phenotype or genotype change? |
Phenotype |
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What is the main method for epigenetics |
DNA methylation |
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How does DNA methylation work as an epigenetic mechanism |
Methylation repressed gene transcription, difficult to break DNA to get a strain so blocks it |
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Other type of epigenetic mechanism |
Histone modification |
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What is genomic imprinting |
Development form of epigenetics where some genes are myelinated based on if their inherited maternally or paternally (switched off) |
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What chromosome shows an example of genomic imprinting |
Chromosome 15 |
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If a gene is maternally imprinted, what does this mean? |
Only express/activate the gene from father |
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What 2 syndromes can chromosomal 15 depletion create |
Prader-Willi syndrome Angelman syndrome |
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How is Prader-willi syndrome caused? |
Deletion on paternal chromosome, only maternal genes present |
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How is Angelmann syndrome caused |
Deletion on maternal chromosome Only paternal gene present |
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What is Prader-Willi syndrome characterised by |
Intellectual disability, decreased muscle tone, short stature, emotional lability and insatiable appetite (can = obesity) |
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What is angelman syndrome characterised by |
Delayed development, severe lang impairment, movement and balance problems, small head, sociable behaviour, frequent smiling |
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Evidence of rats in epigenetics |
Maternal care (pup licking) switches on serotonin, activate transcription factor, switch on gene expressing glucocorticoid receptor (GR). Absense of licking: no transcription factor, promoter methylated - gene becomes methylated = low levels of GR loss of GR feedback in HPA axis = ^ stress hormones, ^ anxiety/depression |
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How do transformational epigenetics work? |
Disrupted histones in sperm cells (e.g. smoking/drinking) showed alterned RNA profile in offspring and grand-offspring |
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What % of our DNA is shared |
99.9% |
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What are natural variations in our DNA known as |
Single Nucleotide Polymorphisms (SNPs) |
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What has looked for what SNPs soetbwith disease state |
Genome wide association studies (GWAS) |
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What is a functional SNP |
A SNP that has an effect on expression (by itself) |
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What's a genetic tagging SNP |
A SNP that is associated with a functional change if next to a mutation or variant that is important |
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What disease can be explained via polygenic, different variants |
Alzheimer's |
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What SNP differences are shown through Alzheimer's disease |
APOE3 and APOE4 |
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What is the cell body of a neuron called? |
Soma |
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What is found at the end of the axon, location of the synapse, communication point with other neuron |
Terminal button |
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What are the two sides of the phospholipid molecule in neuronal membranes? |
Hydrophillic (likes water) Hydrophobic |
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What acts as a framework, holding up the shape of the cell in the neuronal membrane? |
Cytoskeleton proteins |
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What is the resting mebrabe potential? |
-65 to -70 milli Volts |
Inside the cell |
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What have they used to observe the resting membrane potential |
Giant squid axon in sea water |
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What are the two forces that cause a membrane potention |
Diffusion Electrostatic force |
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What is equilibrium potential? |
Diffusion force = electrostatic force |
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What ions is there more of outside of a neuron? |
Sodium and chloride |
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What ions are there more of inside a neuron? |
Potassium Organic anions |
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During resting state, what forces are acting upon sodium? |
Diffusion and electrostatic forces pulling sodium into the neuron |
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During resting state, what forces are acting upon potassium? |
Diffusion pushing potassium out of the cell Electrostatic keeping in the cell |
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During resting state, what forces are acting upon chloride |
Diffusion pulling Chloride into the cell Electrostatic pushing out |
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3 names for the things that allow ions to move into/out of the cell |
Ion channel Leak channel Resting channel |
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Why is the overall resting membrane potential negative |
Way more potassium channels open than sodium channels More possibility for potassium to leave than sodium to enter Resting membrane potential more towards potassium membrane potential |
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What is used to calculate the equilibrium potential? |
The Nernst equation |
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What does the Nernst equation take into account |
Body temperature |
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What maintains the sodium and potassium gradients across the membrane? |
Sodium-Potassium pump |
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What is broken down to release energy which forces the ions to move against their concentration gradient |
ATP |
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Where is an AP generated |
Axon hillock |
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How is an AP generated |
Either by summation of converging inputs from the dendrites or by electrical stimulation (experimentally) |
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Whats it called when membrane potential becomes more negative than RMP |
Hyperpolarisation |
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Whats it called when membrane potential becomes more positive than RMP |
Depolarisation |
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What is it called when following a small stimulation of a neuron there is a small degree of depolarisation that decays along the length of the neuron? |
Decremental conductance |
Decay |
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What opens when the membrane becomes depolarised |
Voltage gated channels |
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What has been used to look at propeties of voltage gated channels |
Voltage clamp experiments |
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Positive membrane potentials (very high degrees of depolarisation) result in what for the channels |
Inactivation of the Na+ channels |
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Depolarising a neuron by +23mV leads to what (as shown by voltage clamp experiments) |
Transient inward current followed by a slow outward current Sodium current: fast (in) Potassium current: slow (out) |
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What is conductance |
The rate of ion travel through channel |
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What are the 3 states of the voltage gated channels |
Closed Open Refractory |
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What causes refractory periods in voltage gated channels |
Inactivation gate closes after activation gate opens |
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When does sodium voltage gated channels not allow for activation (in an AP) |
If +50/65 membrane potential/lots of depolarisation, goes straight into refractory |
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How are potassium gated channels different to sodium gated channels? |
A lot of depolarisation opens the channels |
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In an AP, what is the first movement of potassium and why |
Moves out of the neuron by diffusion |
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What is it called when the sodium channels hit refractory and potassium still leaves the neuron? |
Repolarisation |
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What causes the hyperpolarisation? |
Few remaining open K+ channels and high concentration of K+ outside of the neurone |
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After hyperpolarisation, what happens? |
Na+/K+ pumps work like mad to restore RMP |
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What happens to the potassium left outside the cell? |
Diffuses away |
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What is propogation for unmyelinated axons? |
Unidirectional |
Direction |
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What is the bit inbetween myelin called |
Nodes of Ranvier |
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When an axon is myelinated, where does an AP occur |
Only at nodes of Ranvier |
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Whar happens to the depolarisation caused by AP in myelinated sections |
Decays |
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What are the advantages of myelinated axons? |
Less APs are needed to send a nerve impulse APs require energy (e.g. sodium-potassium pump activations) and time |
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What is multiple sclerosis? |
Disease where neurons have damaged myelin sheath Leads to: Loss of sensitivity, muscle weakness, difficulty with coordination and balance |
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Where is the toxin tetrodoxin (TTX) found? |
Puffer fish |
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What does the toxin tetrodotoxin (TTX) do? |
Blocks voltage gated Na+ channels, leads to paralysis then death |
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Where is the toxin alpha- dendrotoxin found |
Green mamba |
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What does the toxin alpha-dendrotoxin do |
Blocks voltage gated K+ channels leading to convulsions |
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What are the 2 types if synapses |
Electrical synapse Chemical synapse |
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What are the 3 types of synapses |
Axodendric Axosomatic Axoaxonic |
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What is the most common type of synapse |
Axodendritic |
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Lots of inhibitory connection are which synapse |
Axosomatic |
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Why does synapse location matter |
EPSP (excitatory post synaptic potentials) decay along dendrite (decremental decay) |
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Where are EPSPs and IPSPs summated? |
Soma (cell body) |
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When APs get to a synapse, depolarisation opens what? |
Voltage-gated calcium channels |
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What does an influx of calcium im the presynaptic terminal lead to |
Neurotransmitter release |
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Neurotransmitters binding to and activating receptors on the dendrite of the postsynaptic cell leads to what |
Depolarisation (excitation) or hyperpolarisation (inhibition) of the postsynaptic cells |
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If summation shows there is enough depolarisation, what happens |
AP is generated at the axon hillock |
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What is Dales law |
If a particular neurotransmitter is released by one of a neurons synaptic endings, the same chemical is released at all synaptic endings of that neuron |
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What are neurotransmitters stored in presynaptically |
Vesicles |
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4 steps of neurotransmitter release |
Depolarisation Calcium influx Vesicle infusion Detatch/move away from dock |
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2 types of receptors on the postsynaptic membrane |
Ionotropic receptor Metabotropic receptor |
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Structure of an ionotropic receptor |
Protein subunits around a central pore |
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How quick is the transmission in ionotropic receptors |
Fast- immediate change |
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How can ionotropic receptors have inhibitory/excitatory effects? |
Excitatory = +ve ions move into the neuron e.g. glutamate, depolarising Inhibitory = -ve ions move into the neuron e.g. GABA-A receptors, hyperpolarising |
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How do Metabotropic receptors work? |
Neurotransmitter binds to receptor and activates the G-protein couples receptor GTP replaces GDP The G-protein splits and activates other enzymes Breakdown of GTP turns off G protein activity Series of chemical reactions leads to amplification of the signal - second messenger system |
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How quick is the transmission in metabotropic receptors |
Slow but bigger effects |
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What stops neurotransmitters |
Deactivating enzymes |
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What are the 5 different classes of neurotransmitters |
Amino acids Monoamines Soluble gases Acetylcholine Neuropeptide |
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Endorphins are part of what class of neurotransmitter? |
Neuropeptides |
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Serotonin, dopamine, norepinephrine and epinephrine are part of what class? |
Monoamines |
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Glutamate and GABA are part of what class of neurotransmitters |
Amino acids |
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What are 2 neural integrations boosting EPSPs (name and explanation) |
Spatial (multiple excitatory inputs at the same time on dendrite from dif axons) Temporal (multiple excitatory inputs at different time on dendrite from same axon) |
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Where are autoreceptors located |
Presynaptic terminal |
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What is the role of autoreceptors |
Regulate internal process controlling the synthesis and release of neurotransmitter Negative feedback mechanism |
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What are autoreceptors not the same as |
Reuptake sites |
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Are autoreceptors ionotropic or Metabotropic? |
Metabotropic (G-protein coupled) |
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What is neuromodulation? |
Alter the presynaptic cell's ability to release more transmitter or the postsynaptic cells ability to respond |
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Where are amino acids, monoamines and acetylcholine synthesized? |
Locally in presynaptic terminal |
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Where are neuropeptides synthesized? |
Cell soma (transported to the terminal) |
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What does neuropeptides need |
Way more calcium globally, not just locally |
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4 criteria for neurotransmitters |
Created presynaptically Electrical stimulation leads to release Physiological effect Termination |
CEPT |
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What does too much glutamate/too little GABA cause |
Hyperexcitability - epilepsy Excitoxicity (cell death response in the brain) |
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What else causes excitoxicity? |
Cerebral ischemia (insufficient blood flow) |
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Terminology for what transmitter binds to the receptor and how drugs interact |
Pharmacology |
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Receptors vary in what 4 things |
Pharmacology Kinetics Selectivity Conductance |
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What is kinetics |
Rate of transmission binding and channel gating (determine the duration of effects) |
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What are receptors selectivity |
What ions are fluxed |
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Whats a receptor's conductance |
The rate of flux |
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What does glutamate ionotropic receptors flux |
Na+ |
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What does GABA ionotropic receptors flux? |
Cl- |
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3 types of ionotropic glutamate receptors |
NMDA receptor AMPA receptor Kainate receptor |
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Differences between AMPA and NMDA receptors |
Binding of glutamate alone leads to opening for AMPA NMDA requires a co-agonist: glutamate and glycine, as it is blocked at rest by Mg2+ Voltage-dependent blockage (depolarised e.g. -30mV pushes Mg2+ out, REQUIRED) NMDA also permeable to Na2+, K+, Ca2+ (AMPA = Na2+, slightly K+)
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4 main things |
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Difference in kinetics of AMPA and NMDA receptors |
Slower kinetics of NMDA meaning channels stays open longer AMPA = fast |
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Conductance of AMPA and NMDA |
Ampa- fast (rate of flux) NMDA - slow (rate of flux) |
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Blocking NMDA receptors by drugs leads to what |
Symptoms that resemble the hallucinations associated with schizophrenia |
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What else does dysregulation of NMDA receptors cause (not schizo) |
Glutamate excitoxicity (excessive Ca2+ influx) |
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What is GABA synthesized from? |
Glutamate |
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Whats the effects of too much GABA? |
Sedation/coma |
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At the right dose, what can drugs that increase GABA transmission be used to treat? |
Epilepsy |
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2 GABA agonists |
Alcohol Barbituates |
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What are the 2 main families of GABA receptors |
GABA-A ionotropic receptors GABA-B metabotropic receptors |
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What is the structure of GABA-A receptors |
Heteropentameric structure - 2 alpha + 3 more subunits (beta, gamma or delta) 6 possible subunits (Can have 1 alpha i think) |
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Function of GABA-A receptors |
Increases chloride permeability and hyperpolarises the neuron Decreasing the depolarising effects of an excitatory input |
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Name of an agonist binding at GABA binding sites that makes people "drunk worse than vodka" |
Muscimol |
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What is an indirect GABA agonist |
Benzodiazepines |
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What do drugs increasing GABA activity reduce? |
Anxiety |
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Name of a GABA antagonist that increases anxiety |
Flumazenil |
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Patients with panic disorder have less what? |
Benzodiazepine binding sites |
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Barbiturates how what effect on the RMP with GABA |
More hyperpolarisation |
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Problems with barbiturates |
General depression of neuronal activity includes vital functions like breathing Poor therapeutic ratio, OD easily, high suicide risk. LT treatment = dependence and withdrawal |
3 things |
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What is barbiturates used for now |
Insomnia and seizures |
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Benzodiazepines use (5) |
Anxiolytic Anticonvulsant Sedative Muscle relaxant Amnestic |
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Examples of neuromodulating neurotransmitters |
Dopamine Serotonin Noradrenaline Acetylcholine Histamine Neuropeptides |
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What does FM and AM stand for |
Frequency modulation Amplitude modulation |
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2 exceptions to the rule that the effect of a neurotransmitter is ultimately determined by receptor type |
Some neurotransmitters act as neuromodulators (GABA at GABA-B receptors) Some neuromodulators act as neurotransmitters (ACh at ACh receptors) |
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4 diffuse modulatory systems |
Dopamine Serotonin Noradrenaline Acetylcholine |
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Where does dopamine originate |
Ventral Tegmental Area (VTA) and substantia nigra in midbrain |
2 places |
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3 dopamine systems/projections names |
Nigrostriatal system Mesolimbic system Mesocortical system |
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Role of dopamine in the nigrostriatal system |
Movement |
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Dysfunction in the nigrostrial system could lead to what |
Parkingsons disease Huntingtons disease |
2 things |
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Role of dopamine in the Mesolimbic system |
Reinforcement (reward) |
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Dysfunction in Mesolimbic system could lead to what |
Addiction (enhanced DA release in NAcc) |
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Role of dopamine in mesocortical system |
Working memory and planning |
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Dysfunction in the mesocortical system could lead to what |
Schizophrenia/addiction |
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What esssential amino acid is dopamine from |
Tyrosine |
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What is tyrosine catalysed by |
Tyrosine hydroxylase |
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What does tyrosine catalysed lead to |
L-Dopa |
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3 ways for controlling the amount of dopamine |
Feedback inhition (too much dopamine lowers tyrosine hydroxylase (TH)) = down regulation of synthesis DA release leads to phosphorylation of TH increasing activity (feedback still)= up regulation of synthesis (replenish pool) Prolonged activity in the presynaptic neuron leads to increase in transcription of the TH gene = up regulate (increase size of pool) |
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What effect does Reserpine have |
Impairs storage of monoamines in synaptic vesicles Causes catalepsy (look soulless, trouble moving) |
Rabbits |
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What is L-DOPA used to treat |
Parkinsons |
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What drug inactives TH |
AMPT |
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How do cocaine, amphetamine and methylphenidate work |
Block the reuptake of monoamines into terminals |
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Where does the noradrenergic system project from? |
Locus coerulus |
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Role of the noradrenergic system |
Arousal and attention |
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What 3 things is dysfunction in the noradrenergic system linked to? |
Anxiety Heroin withdrawal Depression |
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5 functions of serotonin systems |
Mood Sleep Pain Emotion Appetite |
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What amino acid is serotonin made from |
Tryptophan |
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What is trytophan broken into |
5-hydroxytryptophan (5-HTP) |
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What is the rate limiting stage in dopamine synthesis |
Tyrosine hydroxylase catalyzing |
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What is the rate limiting step in serotonin synthesis |
Tryprophan obtaining |
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What complex is involved in the cholinergic systems projections to hippocampus and cortex? |
Basal forebrain complex |
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What neurons project locally in the striatum and cortex |
Cholinergic interneurons |
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What is the rate limiting step in acetylcholine synthesis |
Amount of choline |
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What is acetylcholine rapidly degraded in synaptic cleft by |
Acetylcholinesterase (AChE) |
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AChE inhibitors have helped what |
Treatments for Alzheimers disease Myasthenia gravis (autoimmune disorder) |
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Botox acts where |
Directly at synapse in Neuro-Musclular Junction |
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Where is ACh released |
Neuro-Musclular Junction (NMJ) |
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Where does tetanus toxin work |
Inhibitory (glycine) synapses on chlinergic motor neurons of spinal cord |
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What does tetanus toxin do |
Disinhibits the cholinergic neurons so they continuously fire resulting in permanent muscle contraction |
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What is the mechanism underlying synaptic strengthening |
Long term potentiation |
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What part of the brain was LTP first observed/studied |
Hippocampus |
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3 properties of LTP |
Temporal = summation of inputs reaches a stimulus threshold that leads to the induction of LTP e.g. repetitive stimulation (HFS). Associative = simultaneously stimulation of a strong and weak pathway will induce LTP at both pathways (spatial summation). Specific: LTP at one synapse is not propagated to adjacent synapses (input specific). |
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What's happening at the synapse before LTP? (Small activation) |
Glutamate release onto inactive cell (membrane resting) AMPA receptor activated NMDA blocked by Mg2+ Depolarisation (from AMPA) not enough to expel Mg2+ |
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Whats happening at the synapse during high activation (freq activation or neighbouring cell) during LTP? |
Glutamate release onto an active cell (membrane depolarised) AMPA receptor activated Mg2+ block relieved Na+ through AMPA and NMDA Ca2+ through NMDA |
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What does the Ca2+ that has entered through the NMDA receptor in LTP do? |
Activate CaMKII |
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What does CaMKII do? |
Phosphorylate existing AMPA receptors increasing their effectiveness Stimulates the insertion of new AMPA receptors into the membrane |
2 things |
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How does CaMKII have sustained activity after repolarisation |
Phosphorylates itself Molecular switch maintaining increased excitability of neuron for minutes to hours |
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What are the presynaptic events in LTP |
Postsynaptic neuron feeds back to presynaptic neuron by retrograde neurotransmitter - nitric oxide Leads to increased glutamate release |
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What is required for long-lasting LTP |
Protein synthesis |
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What is a transcription factor involved in late phase LTP |
CREB |
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What is CREB phosphorylated by |
Kinases e.g. PKA or CaMKII |
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What does late phase LTP do |
Can involve morphological changes and the establishment of new synapses |
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How long does early phase LTP last for |
Minutes to an hour |
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How long does late phase LTP last for |
Hours, days or months |
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What are silent synapses? |
Synapses with only NMDA receptors |
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What is the process of recruiting new synapses in LTP? |
EPSPs lead to unused AMPA receptors being recruited, spreading to neighbouring synapses, turning on silent synapses. Synapses also may split into 2, increasing the number of them |
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What is the opposite of Long Term Potentiation |
Long Term Depression |
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How is Long Term Depression caused |
Low frequency stimulation |
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What happens to AMPA receptors in Long Term Depression |
Dephosphorylated and removed from the membrane |
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What causes the AMPA receptors to be dephosphorylated in LTD |
Same NMDA process, however lower level rises in Ca2+ activate phophatase rather than kinase |
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What did the Morris Water Maze show |
Hippocampal lesion rat does not learn where platform is NMDA antagonist swims like it has no hippocampus |
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What did Bear show when test LTP on human inferotemporal cortex removed during surgery |
High Frequency Stimulations = LTP LFS = LTD |
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What is the issue with titanic stimulation |
Artificially high stimulation |
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Is there a physiological equivalent to tetanic stimulation? |
Yes - hippocampus theta rhythms |
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When do theta waves become active |
When animal is active - running, swimming, head movements and spatially orientated response Arousal/alertness, fire during exploration etc |
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Depolarising stimulation of a neuron at a peak of a theta waves leads to what? |
LTP |
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Depolarising stimulation of a neuron at a through of a theta waves leads to what? |
LTD |
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Genetically increasing the amount of NMDA shows what in Morris Water Maze |
Boosts LTP and significantly increased rate in learning Spend more time in quadrant where platform is in probe trial |
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Aging shows what in the Morris Water Maze |
Decreased acquisition in the Morris Water Maze (takes longer to learn) Decreased LTP Decreased expression of the NMDA receptor |
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How does enrichment effect the Morris Water Maze? |
Enhanced acquisition Increased LTP |
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One suggestion to how to reverse aging effect on LTP |
Enrichment |
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Evidence of enrichment reversing effect on aging |
Spatial maze task: Old mice in impoverished environment show greater deficits than those in standard or enriched conditions. Can change via environment change. |
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Associative LTP entails what summation? |
Spatial summation |
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What has been used to prove LTP underlies fear memories (not just correlational) |
Optogenetics (shining lights on neurons that have been modified to respond to light) |
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How can you engineer a memory with LTD and LTP |
Instead of using tone, use optogenetics, with shock and can elicit same response of fear/freezing. Fire lots of light (high freq stim) = LTP, fire little light (LFS) = LTD |
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Increasing NMDA function in the forebrain leads to what? |
Improved spatial memory |
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What do patients of panic disorder lack in the brain? |
Sufficient inhibitory control in cortical and limbic regions to suppress inappropriate fear responses |
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GABA-A antagonist |
Flumazenil |
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How do benzodiazepines work on GABA |
Makes it more effective at opening the Cl- channel Greater influx of chloride Greater hyperpolarisation More inhibition |
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What does benzodiazepines do at GABAa receptors with no GABA |
Nothing (no opening of channel) |
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What does anxiolytic mean |
Reduce anxiety |
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Are GABA agonist anxiolytic or anxiogenic |
Anxiolytic |
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What is the problem with barbiturates |
Activitate all GABA-A = shut down effect |
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Partial agonists have a better what |
Therapeutic ratio |
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Where is there a high density of alpha 2 GABAa receptors |
Limbic system Hippocampus Amygdala |
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2 animal model to study anxiety |
Elevated + maze Conditioned Emotional Response test |
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What is the effect of diazepam on the elevated + maze |
Increases amount of time spent in the aversive open arms of the maze |
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What did using an agonist at alpha 2/3 subunit of GABAA receptors show for the elevated + maze? |
Spent equivalent/possibly greater time in open arms of maze than general diazepam showing they are the ones influencing anxiety |
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What is the process of the conditioned emotional response |
Train mice to press level for food Learn 2 things= Bell paired with mild footshock Just a light (no consequence) Change in level pressing ratio: how much pressing when bell played/pressing when light + pressing when bell |
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What is the effect of agonist at a2/a3 subunit containing GABAa receptors on the conditioned emotional response task |
More agonist = less suppression (less change in pressing) More anxiolytic |
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What is the effect of removing alpha 2 subunits (knockout) in mice for the conditioned emotional response task? |
No difference in acquisition or lever pressing for food Knockouts show greater supression (more anxiety?) than wildtypes |
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What is the effect of benzodiazepines on GABAa a2 subunit knockout mice in the conditioned emotional response task? |
No effect (doesn't reduce supression) |
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Benzodiazepines are dependent on what part of the structure of an alpha subunit |
Histidine |
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What is it called when you change the DNA sequence so that GABA-A a2 subunits have an argenine rather than a histidine |
Knock in |
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What difference did a knock in mice for GABA-A alpha 1 show as a response to diazepam |
Lost sedation effects and reduced Anticonvulsant effects |
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What difference did a knock in mice for GABA-A alpha 1 show as a response to diazepam |
Lost sedation effects and reduced Anticonvulsant effects |
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What difference did a knock in mice for GABA-A alpha 2 show as a response to diazepam |
No anxiolytic effect |
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What is the anxiety effect of a barbiturate in GABA-A subunit alpha 2 knock in mouse and what does this show |
Still works - have the same anxiolytic effect Show alpha 2 containing receptors still there just not effected by BZD |
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What difference did a knock in mice for GABA-A alpha 3 show as a response to diazepam |
No difference |
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Want to find selective BZD agonist that acts specifically where? |
A2 receptors |
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What is a syndrome that leads to little/no fear when both right and left medial temporal lobes of brain malfunction |
Kluver-Bucy syndrome |
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What did SM case study have |
Bilateral amygdala lesions |
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What did SM case study show |
Fear response significantly reduced compared to normal |
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Where is the amygdala |
Deep in brain of temporal lobes |
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What subjects show increased amygdala activation during public speaking vs control |
Subjects with social anxiety disorder |
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What is there a high density of in the amygdala |
Benzodiazepine binding sites |
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Injection of soluble BZD into amygdala induces what |
Anxiolytic effect |
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After amygdala destruction, does BZD have an effect and what does this show |
Yes, some, anxiety controlled by other brain areas as well |
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What 2 things does the amygdala excite? |
Locus coeruleus + hypothalamus |
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What does the H stand for in HPA axis? |
Hypothalamus releases CRH |
What it does |
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What does the P stand for in HPA axis? |
Pituitary releases ACTH |
What it does |
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What does the P stand for in HPA axis? |
Pituitary releases ACTH |
What it does |
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What does the A stand for in HPA axis? |
Adrenal cortex release cortisol (stress hormone) and adrenaline |
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In fear response, what does the locus coerulus release |
Noradrenaline |
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What part of the brain provides info about contextual stimuli that are important for fear condition |
Hippocampus |
Lesions here have anxiolytic effdcg |
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Increasing GABA inhibitions in hippocampus leads to what |
Decrease in contextual fear response (freezing less in context learnt) |
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What effect does noradrenaline have |
Increases arousal and attention |
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What effect does benzodiazepines have on Locus coeruleus? |
Decrease its release of Noradrenaline (increase GABAergic inhibition) |
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What balances the adrenaline (arousal) |
Raphe nuclei (serotonergic projections) = behaviour inhibition, freezing |
Freezing |
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What do benzodiazepines do to the serotonin activity |
Decrease it in the raphe nuclei |
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Benzodiazepine effect on serotonin evidence |
Increase in social interaction in rats following midazolan administered directly into the raphe nuclei |
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What disorders do benzodiazepines work well on |
GAD Panic D |
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What disorders do benzodiazepines not work well in |
OCD PTSD |
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What is a common treatment for all 4 anxiety disorders |
SSRIs |
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What is the pattern of effect for SSRIs |
Can be anxiogenic in short term (first few days) Anxiolytic effect may not become apparent for weeks |
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What is another common treatment for GAD that takes 4-6 weeks to exert therapeutic potential |
Buspirone (5-HT 1A receptor partial agonist) |
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Why do SSRIs take a few days to work? |
Presynaptic receptor feedback to presynaptic cell to stop making serotonin as already some in synapse |
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Why does buspirone take a few weeks to have an effect? |
Autoreceptors decrease 5-HT cell firing, changes in brain LT |
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Main role of acetylcholine |
Attention/learning |
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What type of receptors do neuromodulators activate? |
Metabotropic |
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What gated ion channels are ionotropic receptors |
Ligand |
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Which type of acetylcholine receptors are ionotropic |
Nicotinic |
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Which GABA receptor is Metabotropic? |
GABA B |
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Term for transfering signals into cell |
Transduce |
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Stages of activation of Metabotropic receptors in signal tranduction cascade |
G protein ⬇️ Effector protein ⬇️ Second messenger ⬇️ Kinase ↙️ ↘️ Channelactivation Genetranscription |
5/6 |
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How was ionotropic receptors discovered/named |
Pharmacology (effects of drugs) |
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How were dif G protein coupled receptors discovered? |
Cloned by homology (screening dif DNA), work out which ligands were binding or which neurotransmitter were specific to activate each of those dif receptor subtypes |
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Neurotransmitter binding to the extracellular domain of a Metabotropic receptor causes what |
Uncoupling of a heteromeric G protein on the intracellular surface (allowing them to move freely) Signal is transduced across the cell membrane |
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What are the components of a G protein |
Subunits alpha, beta and gamma |
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When a G protein is not active, what does it have attached to it? |
GDP molecule |
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What replaces the GDP molecule when a ligand is bound to the receptor |
GTP |
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What does the G protein split into |
Alpha subunit + GTP Beta and gamma subunits |
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What happens to the GTP attached just to the alpha subunit |
Converts to GDP after some time, switching off the activity |
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3 types of alpha subunits |
Gs stimulates adenylyl cyclase Gi inhibits adenylyl cylase Gq stimulates phosphate C |
And what they do |
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What do beta gamma complexes activate |
K+ channels directly |
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What does stimulating the Gs protein stimulate the synthesis of? |
cAMP |
(Second messenger) |
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What does cAMP activate |
Protein Kinase A (PKA) |
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What is the opposite of protein kinase |
Protein phosphatase (takes off phosphorylate group) |
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What does phosphorylating do? |
Increases the effectiveness of the channel (allowing it to open more/easier) |
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Does one transmitter bound receptor uncouple one G protein |
No, can uncouple multiple |
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2 names of types of presynaptic receptors |
Autoreceptors Heteroreceptors |
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How does the presynaptic dopamine receptor activation work |
Phosphorylates tyrosine hydroxylase (increase dopamine) Phosphorylates K+ channels (channels open, hyperpolarisation, further release of vesicles inhibited - promotes phasic release (big bursts)) |
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Difference between autoreceptors and heteroreceptors |
Auto- regulate own neurotransmitter release Hetero - modulate release of another transmitter |
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Example of a heteroreceptor |
Nicotinic receptors - ligand gated ion channel flux Ca2+ activation lead to release of dif transmitter (e.g. dopamine) |
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What 2 types of longterm synaptic changes can signal transduction/second messenger cascades lead to? |
Structural and biochemical |
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What 2 ways do neuropeptides differ from other kibds of neurotransmitters |
Methods of synthesis (cell body) And release (global Ca2+) |
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What is the structure of neuropeptides? |
Short polypeptide chains (6 to 36 amino acids) |
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Neuropeptides are produced by cleavage of what? |
Propeptides synthesized directly from mRNA |
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The hippocampal Theta waves are controlled by what |
Neuromodulatory acetylcholine release in the hippocampus |
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What is an antagonist of muscarinic acetylcholine receptors (metabotropic) |
Scopolamine |
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What does scopolamine do? |
Disrupt hippocampal waves Disrupt learning and memory |
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What system is the first to degenerate in alzheimers disease? |
Acetylcholine system |
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Opioid/opiate receptors agonists |
Opiates e.g. morphine, heroin |
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Opioid/opiate receptors antagonist |
Naloxone, naltrexone |
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Are opioid/opiate receptors ionotropic or Metabotropic? |
Metabotropic |
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2 roles of the opioidergic system |
Analgesia (inability to feel pain) Relaxation (regulating noradrenaline release) |
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Dif between morphine and heroin |
Heroin administered and get to brain in seconds Morphine in minutes |
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How does opiates create the relaxing effect |
Inhibiting the firing of noradrenergic neurons in the Locus Coeruleus |
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Opioid receptors are couple to what G? |
Gi |
You can work it out |
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Withdrawal leads to increased or decreased firing in LC? |
Increase d |
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What is the balance of Gs and Gi coupled receptors during opiate withdrawal |
Lack Gi, hypersensitivity of Gs |
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What is upregulated in tolerance to opiates |
Gs pathway component (to match Gi) |
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Alongside the Gi pathways decreasing PKA and inhibiting the neuron, what does the G(beta gamma) subunit do? |
Activate K+ channels = more inhibition |
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Cascade involved in opioid agonists (morphine) |
Gi coupled opens K+ channel (hyperpolarises) and inhibits the adenylyl cylase = no cAMP = no PKA = no Na+ channel phosphorylation = LC cell inhibited |
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What are the compensatory changes in tolerance of morphine |
Increased expression of adenylyl cyclase Increased expression of PKA (Decrease degradation of PKA) |
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4 components of withdraw process from morphine or Naloxone (mu antagonist) |
Compensatory changes still active No inhibition through mu receptors cAMP pathways overactive LC firing increases above normal levels |
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What are the negative symptoms of schizophrenia |
Flattened emotional response, poverty of speech, lack of initiative and persistence, anhedonia and social withdrawal |
5 |
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What are the cognitive symptoms of schizophrenia |
Low psychomotor speed Problems in sustained attention Deficits in learning and memory Poor abstract thinking Poor problem solving |
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A rare mutation in what gene has been linked to schizophrenia |
DISC1 |
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DISC1 increases the chance of schizophrenia by a factor of what |
50 |
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How does parental age relate to schizophrenia |
Children of older fathers more likely to develop schizophrenia |
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Why are older fathers more likely to have schiz children |
Most likely due to mutations in the spermatocytes (cells that produce sperm) as they divide much more than a woman's oocytes - more change for mutation |
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What % of DZ twins have schizophrenia |
17% |
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What % of DZ twins have schizophrenia |
48% |
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What are the 2 types of MZ twins |
Monochronionic (same placentas) Dichrionic (dif placentas) |
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What is the difference in concordance rates for schizophrenia in dichorionic and monochorionic twins? |
11%-M 60%-D |
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3 neurodevelopmental theories to schizophrenia |
The early neurodevelopmental model The late neurodevelopmental model Two-hit model |
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3 early evidence for schizophrenia suggesting abnormal brain development |
Home movies from families with a schizophrenic child (more -ve affect, more abnormal movements) Danish children videod while eating lunch, blind raters found schiz displayed less sociability and deficient psychomotor functioning Minor physical abnormalities in ppl with schizophrenia |
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What is the late neurodevelopmental model of schizophrenia |
Schizophrenia may result from abnormality in adolescence when synaptic pruning takes place |
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What is the pattern of developmental pruning in schizophrenic people |
Much greater in adolescence |
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Do men or women exhibit schizophrenia later? |
Women |
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3 structural changes in brain due to schizophrenia |
Ventricular enlargement Reduced brain volume (less grey matter) in temporal and frontal lobes and hippocampus Faulty cellular arrangement in the cortex and hippocampus |
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How much bigger is the ventricles in schizo patients |
More than 2x |
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7 neurocognitive deficits in schiz patients |
Lower IQ Planning and info processing deficits Attentional deficits Working memory deficits Sensory-motor gating deficits Antisaccade task (look away from attracting stimulus) Occolomotor function (eye tracking) |
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Weinberger suggested the negative symptoms of schizophrenia are caused primarily by... |
Hypofrontality, decreased activity of the frontal lobes, the dIPFC in particular |
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What task shows attentional deficits in schizophrenic patients |
Stroop test |
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What task shows working memory deficits in schizophrenic people |
Wisconsin card sort test |
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What does the Wisconsin card sort test show neurobiologically in schizophrenic people |
Lack of increase in regional blood flow to the dIPFC (the normal response) = hypofrontality |
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In sensory motor gating deficits, what signal does not diminish when 2 stimuli (clicks) is presented |
P50 |
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In sensory motor gating deficits not learning to inhibit a startle response shows what |
Pre-pulse inhibition (deficit) |
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What is the oculomotor function in schizophrenic people |
Eye movement not smooth, catchup saccades |
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4 neurochemical hypotheses of schizophrenia |
The dopamine hypothesis The glutamate hypothesis Neuroinflammatory hypothesis The estrogen hypothesis |
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What is the prevalent theory of schizophrenia |
Dopamine |
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Where is there overactivity of dopamine in the dopamine hypothesis of schizophrenia |
Mesolimbic system |
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What does overactivity of dopamine in the mesolimbic system result in |
+ve symptoms |
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Where is there underactivity of dopamine in the dopamine hypothesis of schizophrenia |
Mesocortical system |
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What does interactivity of dopamine in the mesolimbic system lead to? |
Negative and cognitive symptoms of schizophrenia |
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What do DA agonists do |
Produce symptoms that resemble the +ve symptoms of schizophrenia |
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4 types of DA agonists |
Amphetamine Cocaine Methylphenidate L-DOPA |
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What was the first DA antagonist |
Chlorpromazine (CPZ) |
For schizo (typical) |
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What do DA antagonists do |
Block D2 receptors |
(Chlorpromazine) |
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What does affinity mean (drug talk) |
How well it binds to receptor |
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What did a radioactive tracer of IBZM show for schizophrenic people |
More displacement of IBZM, showing more DA activity in striatum correlated with positive symptoms |
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What are the consequences of LT drug treatment of schizophrenia |
Symptoms relating to Parkinson's: slowness in movement, lack of facial expression and general weakness. In around 1/3rd patients = tardive dyskinesia (unable to stop moving, usually around face: smacking of lips or protusion of the tongue) |
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How do newer, atypical antipsychotic drugs work |
Have a lower affinity for the D2 receptor (so no extra-pyramidal side effects) |
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What do atypical antipsychotic drugs help with (for schizophrenia) |
Improve positive and negative symptoms of schizophrenia. Improve the performance in neuropsychological tests. |
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What was the first atypical antipsychotics (the king) |
Clozapine |
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3 issues with the dopamine system |
It explains only a part of schizophrenia (+ve symptoms) Atypical drugs work better Under activity of dopamine in mesocortical pathway, not over, causes -ve symtpoms |
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Which of the receptors are linked to schizophrenia in the glutamate hypothesis of schizophrenia? |
NMDA |
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Mutations in what two gene codes for NMDA receptors could cause schizophrenia |
GRIN1, GRIN2A |
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Is it the glutamate hyperfrontality or hypofrontality hypothesis? |
Hypofrontality |
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What could the NMDA receptor hypofrontality explain? |
Why there are so many treatment resistant negative symptoms Why the onset is in early adulthood and, Why the disorder is associated with structural changes and cognitive deficits |
3 things |
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What 2 drugs can cause all symptoms of schizophrenia |
PCP and Ketamine |
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What antagonists and PCP and Ket |
NMDA |
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What did a monkey administered with repeated PCP show |
Decrease in activity in PFC, showed deficit in task where had to reach around a barrier to get a piece of food (same as those with lesion to PFC) |
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What is the explanation of positive symptoms from the glutamate hypothesis? |
Glutamate stimulates GABA GABA hypofrontality so does not inhibit Glutamate Disinhibited glutamate stimulates overproduction of dopamine |
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What is the explanation of the negative and cognitive symptoms of schizophrenia from the glutamate hypothesis |
Glutamate hypofrontality NMDA synapse GABA not able to inhibit Disinhibted glutamate GABA over excited in VTA Overinhibiting (silence) dopamine signal Reducing the dopamine production in PFC = -ve and cog symptoms |
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What is the Neuroinflammatory hypothesis of schizophrenia |
Hyperactivation of microglia (brain's immune system) |
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Evidence for the Neuroinflammatory hypothesis of schizophrenia |
PET imaging shows increase in microglial activity as severity of illness increases Symptoms reversed with antipsychs/antibiotics that reduce microglial activation Chromosome linked with schizophrenia includes gene region involved in acquiring immunity |
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There are gender differences in schizophrenia in regards to: |
Rate and onset of disease (later in women) Severity and progression (less severe) Response to antipsych treatment (better) |
3 things |
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What % of the population have depression |
5% |
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Different in rates of depression in males and females |
3x more likely in women than men |
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What % heritability is depression? |
37% |
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2 hypotheses to the cause of depression |
The monoamine hypothesis The stress-diathesis Hypothesis (Neurogenic Hypothesis) |
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What is the prevalent theory for depression cause |
The monoamine hypothesis |
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4 types of monoamines |
Dopamine Serotonin Norepinephrine (noradrenaline) Epinephrine (adrenaline) |
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What breaks down monoamine in the synapse |
Monoamine Oxidase (MAO) Catechol-O-methyltransferase (COMT) |
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Early evidence pointing towards chemical inbalance |
Lower levels of the 5-HT, dopamine or norepinephrine metabolite (bit left over when monoamine broken down) in the CSF of depressed individuals |
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Evidence from reserpine for the monoamine hypothesis for depression |
Used to treat blood pressure Caused dep as a side effect Blocks packaging of monoamines into the vesicles, so when the neurons are activated no neurotransmitter is released Rabbits |
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All effective antidepressants affect what system |
5HT/NA |
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What drugs created linked to monoamine hypothesis for depression |
Monoamine oxidase inhibitors (MAOIs) |
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What side effect does MAOIs lead to |
Increased symathetic system stimulation and the cheese effect - cheese type products contain tyramine broken down by MAO in liver, not broken down = stimulation of sympathetic system |
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3 other antidepressants besides monoamine oxidase inhibitors |
Tricyclic antidepressants SSRIs (prozac) SNRIs serotonin- norepinephrine reuptake inhibitors |
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What do tricyclic antidepressants do |
Inhibit the reuptake or serotonin and norepinephrine |
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What do monoamine oxidase inhibitors do |
Inhibit the breakdown of monoamines in the presynaptic terminal so they increase the level of monoamines taken up into the vesicles |
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2 issues with the monoamine hypothesis of depression |
Decrease in serotonergic activity in healthy people doesn't induce depression, only those w/ history. (Cocktail depleted of tryptophan) Time-course, SSRIs and SNRIs increase levels of 5HT or NE rapidly, but effect takes several weeks |
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What shrinks with the duration of untreated depression |
Hippocampal volume |
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What is the negative feedback look in HPA |
Amydgala encourages HPA to create cortisol Cortisol detected in hippocampus, inhibiting the HPA to create cortisol |
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What does chronic stress lead to |
Chronic activation of glucocorticoid receptors = increased Ca2+ into neurons, too much = excitotoxic = cell die Hippocampus can't feedback to limit cortisol production |
Hippocampus |
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Evidence for the dysfunctional stress system in depression |
Artificial cortisol in normal controls activates GR and the negative feedback system, leading to decreased ACTH and cortisol In depressed, they are less sensitive to it (poor -ve feeback), more sensitive to ACTH |
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What is the stress-diathesis explanation of why antidepressants take 2-4 weeks to have an effect |
Takes a while for "newborn" cells to grow |
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Injections of what in the rat brain reduces neuronal death and protects neurons that have been treated with neural toxins |
BDNF |
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Chronic stress does what to the levels of BDNF |
Decreases them |
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What has been used to explain susceptibility to depression |
Serotonin transport |
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Which serotonin transporter has a big interaction with stressful life events and depression |
Short/short (s/s) alleles from parents |
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2 other benefits of having long alleles for serotonin transporters |
More likely to respond to treatment Much better LT outcomes Tryptophan deletion less likely to produce symptoms |
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What is a novel antidepressant? |
Ketamine |
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What antagonists is Ketamine |
NMDA |
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2 alternative therapies to antidepressants |
Transcranial Magnetic Stimulation (TMS) Electroconvulsive Therapy (ECT) |
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Difference between pharmacokinetics and pharmacodynamics |
K = drug movement, entering our body, what our body does to the drug D = drug change, what the drug does to us, when it binds, how it effects us |
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4 categories of criteria of substance use disorders |
Impaired control Social impairment Risky use Pharmacological - tolerance and withdrawal |
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What is the severity cut offs for substance use disorders |
Mild = 2-3 symptoms Moderate = 4-5 Severe = 6+ |
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Do you need tolerance and/or withdrawal for addiction |
No |
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Which brain system is involed in addiction (structures) |
The mesocorticolimbic dopamine system |
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What is the projections involved in the mesocortolimbic dopamine system |
Dopamine neurons projecting from the VTA to nucleus accumbens and prefrontal cortex |
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What is the role of the mesocorticolimbic dopamine system |
Critical pathway for rewards and reinforcement |
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Natural reinforcers (e.g. food and sex) increase what in where? |
Dopamine in the nucleus accumbens |
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What is the changed set point hypothesis for addiction |
Dopamine in nucleus accumbens have been used for little pleasure, but suddenly used to much more |
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Direct agonists increasing dopamine availability/release in Nucleus accumbens |
Cocaine Amphetamine Nicotine |
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How do cocaine/amphetamine work |
Increase availability of dopamine at synapse by blocking or reversing dopamine transporters |
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How does nicotine work |
Direct excitation of VTA neurons by action at nicotinic receptors (leading to dopamine increase) |
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Indirect agonists increasing dopamine availability/release in NAc |
Opioids Cannabinoids |
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How do opioids/cannabinoids work |
Action at opioid or cannabinoid receptors indirectly leads to modulation of VTA activity E.g. inhibition of GABAergic projections onto VTA neurons allows them to fire resulting in increases of DA release |
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What explains wanting a cigarette when you go into a pub |
Associative learning Coincident firing in NAc induces LTP, strengthening sensory inputs synaptic connections |
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What does the dopamine cascade lead to |
Synaptic re-modelling - increased spines and dendritic branches - enhaced LTP |
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Hypoactivity in what brain areas may underlie inability to control in addiction |
Frontal systems |
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What did the self administration model show for rats |
Damage to nucleus accumbens decreases self-administration of heroin |
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Does cocain or amphetamine reverse the transporter of DA |
Amphetamine |
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What else does cocaine and amphetamine effect (altho dopamine is primary) |
5HT NA |
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How do opiates cascades work |
Act at endogenous opioid receptors (Gi/Go coupled) Inhibitory Decrease adenylyl cyclase activity Lead to open K+ channels and close Na+ channels |
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How does GABA inhibition have an effect/on dopamine (2 ways) |
Disinhibits the DA neurons in VTA Action at opiate receptors in the NAc - independent of DA release |
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What is alcohol an agonist of |
GABAa (inhibitory) |
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What is alcohol an antagonist of |
NMDA |
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How does alcohol have an effect on dopamine in NAc |
Suppression of cortical output No GABA activation in PFC Disinhibited DA neurons in VTA Rewarding n reinforcing in NAc |
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How is alcohol involved in the opiate system |
Naltrexone reduces EtOH (alc) self administration in animals Used as a treatmend to reduce EtOH consumption, relapse and craving |
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Explain the nicotine receptors |
Nicotininc acetylcholine receptors Ligand gated ion channels pre and post synaptically Excitatory |
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How does nicotine effect dopamine |
Activation of nACh receptors on cell body in the VTA (increasing firing) Facilitation of DA release by pre-synaptic receptors in NAc |
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What can block nicotine induced behaviour and self administration |
Opiate and DA antagonists |
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What is the prevalent model for addiction |
Impaired response inbibition and salience attribution model of addiction |
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What is the impaired response inhibition and salience attribution model of addiction |
Weakened top down inhibitory control functions and strengthened bottom up functions are features of the addicted brain |
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What is the heredity of addiction |
40-60% |
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What is the heredity of addiction |
40-60% |
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When does addiction usually begin |
Adolescence |
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3 key subtypes of behavioural impulsivity in addiction |
Inability to inhibit actions Inability to delay gratification Inability to reflect before making a decision |
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2 measurements of impulsivity |
Self-report measures (questionnaires) The Matching Familiar Figures Test |
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The matching familiar figures test shows there are 2 types of impulsivity levels in kids called: |
Impulsives (<10 secs) Reflectives (30-40 secs) |
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What does impulsivity lead to in treatment |
Quicker and more drop out |
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Evidence for impulsivity Predisposing later substance abuse |
Field et al impulsivity in adolescents predicted alc involvement 6m later Converse relationship wasn't observed (alc =/ impulse) |
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What system is involved in movement |
Somatosensory |
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What are the 2 types of skin humans have |
Hairy skin Glabrous skin |
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What test reveals differences in skin sensitivity across the body |
2 point discrimination test |
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What parts of our body are the most sensitive |
Fingers (most) Lips Toes |
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3 main types of somatosensory perception (names) |
Nocioception Hapsis Proprioception |
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What is nocioception perceiving |
Pain and temp |
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What is hapsis perceiving |
Pressure and fine touch |
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What is proprioception perceiving |
Movement and location of the body |
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What is the structure of nocioceptors |
Free nerve endings Damage to dendrite or surrounding cells release chemical that stimulate dendrite and produces an AP |
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What is the similarity between the different haptic receptors |
Mechanical stimulation produces AP |
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What are the 4 layers of haptic receptors in order from surface to deep |
Merkel Meissner Ruffini Pacinian |
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3 key proprioceptors |
Muscle spindles Gogli tendon organs Joint receptors |
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What is a rapidly adapting receptor (meaning) |
Receptor that responds briefly to the beginning and end of a stimulus |
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What is a slowly adapting receptor (meaning) |
Body sensory receptor that responds as long as a sensory stimulus is on the body |
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Does meissner's corpuscle have slow or fast adaption |
Fast |
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Does merkel's disc have slow or fast adaptation |
Slow |
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Is pacinian corpuscle rapid or slow adaptation |
Rapid |
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Does Ruffini have rapid or slow adaptation |
Slow |
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What neurons do the somatosensory info go through |
Dorsal-root ganglion neurons |
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How is the structure of a dorsal-root ganglion cell different |
Dendrite and axon are continuous |
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Which somatosensory neuron/s is/are myelinated |
Proprioceptive and Haptic Neurons |
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What are the 2 key somatosensory pathways to the brain |
Dorsal spinothalamic tract Ventral spinothalamic tract |
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What info does the dorsal spinothalamic tract carry |
Haptic and proprioceptive info |
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Does the dorsal or ventral spinothalamic tract cross immediately in the spinal cord |
Ventral |
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Damage in left side of spinal cord would cause what in each leg |
Left leg- loss of sensation of touch and movement Right leg - loss of pain and temp |
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What shows a break in the spinothalamic pathways |
Monosynaptic reflex e.g. knee jerk |
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What system in involved in balance |
Vestibular |
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What does the vestibular organ contain |
3 semicircular canals Otolith organs (utricle and saccule) |
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The semicircular canals in the ear respond to what movement? |
Angular acceleration (spinning on a chair) |
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Uccicle and saccule respond to what movement |
Linear acceleration (moving head back and forth) |
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What does the primary somatosensory cortex do |
Receive projections from thalamus Begin constriction of perception |
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What does the secondary somatosensory cortex do |
Continue the construction of perceptions Project to the frontal cortex |
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Who was the first to discover and map out the somatosensory homunculus |
Penfield |
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Who refined the somatosensory homunculus into 4 seperate parts |
Kaas |
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What were the 4 separate somatosensory homunculi Kaas found |
Area 1: skin (fast) Area 2: joints, pressure Area 3a: muscles Area 3b: skin (slow) |
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What was the hierarchical organisation of Kaas' somatosensory homunculus |
3a 3b 1 2 |
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What is the components of the hierarchical control of movement |
Neocortex (conscious) Brain stem and spinal cord (automatic) |
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What did Karl Lashley add to the theory of initiation of movement |
Preprogrammed motor sequences |
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Role of prefrontal cortex in movement |
Planning and specifying the goal |
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Role of premotor cortex |
Organises motor sequences (select movements appropriate to the context) |
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Evidence of the premotor cortex involvement |
Monkey study, damage to this cortex shows cannot put motor sequences together |
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Primary motor cortex role |
Produce specific skilled movements |
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Evidence for the frontal lobe involvement in movement |
fMRI shows cerebral fluid blood flow in each area for specific tasks Push a lever = motor Perform sequence of movements = motor and premotor Find route through maze = motor, premotor and prefrontal |
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Who was the first to map out the motor cortex |
Fitsch and Hitzig |
Dogs |
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What is the map called that Penfield created |
Homunculus |
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Whag did Graziano show for the motor coetex |
Used precise stimulation and found recognizable actions Motor cortex represents 3 types of organisation: The part of the body that is to be moved, the spatial location to which the movement is directed, and the movements function |
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Who found the area of motor cortex retains size with rehabilitation/ decreases without if damaged |
Nudo and colleagues 1996 |
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How does info from the motor cortex get to parts of body |
Via corticospinal/pyramidal tracts |
What main tract? |
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What are the 2 corticospinal tracts called |
Lateral Ventral |
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What does the lateral corticospinal tract do |
Moves the limbs and digits on the opposite side of body, crosses at brain stem |
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What does the ventral corticospinal tract do |
Moves the muscles of the midline (trunk) on the same side of the body |
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What are the 2 neurons inbthe spinal columns ventral horm |
Interneurons Motor neurons |
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How are the motor neurons arranged |
Laterally located motor neurons = fingers and hand muscles Intermediate = arms and shoulder muscles Medially = trunk |
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What are the pairs that limb muscles are arranged in? |
Extensor and flexor |
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Does flexor muscles move towards or away from the trunk |
Towards |
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What a good extensor example |
Triceps |
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Whats it called if you have paralysis of the legs and arms |
Quadriplegia |
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What did a monkey flexing with weights show |
Flexor motor neurons fire more |
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What did live imagine of motor cortex using calcium imaging show |
A subset of neurons or a "neuronal ensemble" is activated during behaviour (e.g. running) |
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What is the part of the brain responsible for allowing us to adjust the force of our movements |
Basal ganglia |
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What is the basal ganglia |
Collection of subcortical nuclei within the forebrain Receives input from all areas of the neocortex and limbic cortex Projects back to the motor cortex |
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What is the hypothesis called about the basal ganglia |
Volume hypothesis |
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What acts like a volume dial and projectsbto the motor cortex in the volume hypothesis |
The internal globus pallidus |
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What are the 2 pathways within the basal ganglia |
Direct and indirect |
Names |
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Which neurons do the direct pathway express |
D1R (domapine 1 receptor) |
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What does the direct pathway within the basal ganglia do |
Inhibitory effect of the globus pallidus internal (disinhibition): too much activity leads to overactivity in thalamus and amplified force of movement |
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What does the indirect pathway within the basal ganglia do |
Excitatory effect on globus pallidus internal leading to underactivity in the thalamus and reduced force of movement |
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Damage to the basal ganglia cab produce what 2 main types of symptoms |
Hyperkinetic and hypokinetic symptoms |
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What does hyperkinetic symptoms show and where is it seen |
Excessive involuntary movement Huntington's chorea Hemiballism |
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What does hypokinetic symptoms of basal ganglia damage show and where is it seen |
Paucity of movement Parkinson's disease |
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How does Huntingtons affect the volume hypothesis |
DR2 neurons degenerate Disinhibitted indirect pathway Thalamus overactive |
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What does hemiballism show in the volume hypothesis |
Stroke in the subthalamic nucleus Indirect pathway not working properly so doesn't excite the globus pallidus internal to inhibit the thalamus Involuntary fast movements |
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What is used to relieve the symptoms of huntingtons and hemiballism |
Antipsycha clozapine dopamine blocker |
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What is used as a treatment to parkinsons |
L Dopa |
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How does parkinsons affect the volume hypothesis |
Underactivity of in the direct pathway and overactivity in the indirect pathway More inhinition Turning down of motor activity |
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What did a study using parkinsonian mice show |
Optogenetic activation if D1R expressing striatal neurons improved symptoms |
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How does the cerebellum affect movement |
Acquiring a movememnt skill |
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What is the flocculus involved in in movement |
Eye movement and balance |
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What is the lateral parts of the hemispheres of the cerebellum involved in in movement |
Controls movement of limbs hands feet and digits |
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What are the medial parts of the hemispheres of the cerebellum involved in in movement |
Face and midline of mody |
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3 main motor functions of the cerebellum |
Timing of movements Maintaining movement accuracy Motor associative learning |
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Damage to the cerebellum leads to problems in what 3 tasks |
Tapping along to a metronome Throwing darts using prison goggles Eyeblinks conditioning response after airpuffs |
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