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90 Cards in this Set
- Front
- Back
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Definition of circadian rhythm
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observed biological activity that oscillates under environmental condition with a period length close to but not exactly 24 hours
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Properties of circadian rhythms
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approximately 24 hours, temperature compensating, entrainable (adjusts to the outside environment)
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Side effects of jet lag
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Repeated jet lag can cause shrinkage, decreased reaction time and accuracy and increased mortality
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Which direction is it harder to move in east-to-west or west-to-east?
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It is harder to move west-to-east because it requires circadian rhythm advancement
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Experimental tests of circadian rhythms
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1) Biological clocks increase fitness in chipmunks through predator avoidance
2) Resonance of natural period in comparison periodic input from the confers fitness (competition experiments in cyanobacteria) |
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Example model organisms and structures for circadian rhythms
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Cockroaches exist as model organism
Pineal gland exists as a model structure |
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Definition of entrainment
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stimulus leads to behavioral and physiological changes
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Five factors of entrainment
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1. The period of the circadian oscillator must be modified to equalize with the environmental signal
2. The rhythm must adopt a stable phase angle relative to the en-training signal 3. When released into free-rune the rhythm must begin from its normally entrained phase angle 4. No masking 5. Biological limits: Tmax= tau +/- delay period |
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Zeitgebers
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"time giver": stimulus that acts as an oscillating environmental signal (for example: light, temperature)
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Discrete (non-parametric) model premise
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Light/dark transition at dawn and dusk each day bring about discrete phase jumps in the circadian oscillator so that its period matches 24 hours
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Properties of phase response curve
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-shape of light phase response curve is universal
-delays in the early night, advances in the light night -demonstrate the motion of the pacemaker |
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Phase response curve
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map of the responsiveness of the pacemaker to brief pulses of light at different phases of the circadian cycle
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Why do we have circadian rhythms?
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-incur fitness
-conservation of the phase angle |
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Premise of the continuous (parametric) model
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Environmental light continuously adjusts the period of the pacemaker but alters the velocity so that the period matches 24 hours
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Aschoff's first rule
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noctural animals don't set their rhythm based on light, diurnal animals entrain based on dawn
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Aschoff's second rule
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light acts differently on the circadian clocks of diurnal and nocturnal species by shortening tau of diurnal and lengthening tau of nocturnal species
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Suprachiasmic nuclei in circadian rhythms
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light enters the eye, peels off to the SCN which is connected to vvarious other nuclei
Different expressions of peptide neurotransmitter in the SCN |
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Intrinsically photo-sensitve retinal ganglion cells
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Melanopsin cells
-require some modulation between cells that receive and communication -not all cells are clock cells that determine their own rhythm |
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Genetic expression and circadian regulation
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circadian control of gene expression is not light dependent
Molecular genetics also plays a part in sleep syndromes |
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Confirmation of human biological clocks
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Siffre cave experiments and Aschoff and Wever isolation experiments confirmed tht humans have endogenous biological clocks that affect behavior
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Definition and significance of synaptic plasticity
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Synaptic plasticity= a change in synaptic transmission
Significance= required during development, learning and memory, shapes neural communication |
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Short term plasticity
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Lasts on the order of milliseconds to minutes
--synaptic depression caused by NT depletion --synaptic facilitation caused by presynaptic calcium --post-tetanic potentiation caused by increased presynaptic calcium |
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Long term plasticity
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Lasts at least and hour
-best candidate for information storage mechanism -information stored in the relative weight of synapses -Include LTP and LTD |
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Hebb's postulate
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Neurons that fire together wire together --> coactive neurons increase in synaptic efficiency through physiological changes
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Stent's extension of Hebb's Postulate
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Neural connections weaken when co-inactive or consistently fail to fire post-synaptic action potentials
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Hippocampus and synaptic plasticity
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primary location of LTP/D study especially involved in learning and memory studies (spatial memory in rats)
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Perorant pathway
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projects from the entorhinal cortex to the granule cells of the dentate gyrus
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Mossy fiber pathway
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connects the granule cells of the dentate gyrus to the pyramidal cells in the CA3
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Schaffer collateral pathway
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contains the excitatory collaterals of the CA3 pyramidal cells and connects them to the pyramidal cells in the CA1
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Measurement of synaptic plasticity
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-measure in change of EPSPs size
-can plot the amplitude of slope of the synaptic response to establish baseline |
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Field potential
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measures change in voltage of the extracellular region caused by the temporary imbalance in charges when the ion composition of the extracellular fluid changes in response to cell depolarization
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Bliss and Lomo's description of field potentials
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First described in anesthetized rabbits
Stimulated the peforant pathway with high frequency stimulus and described the increase in synaptic transmission |
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LTP and memory share which characteristics?
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-Persistence: can exist for months In Vivo as demonstrated by Abraham et. al in rats
=Specificity: only inputs active during conditioning are potentiated =Associativity: weak input requires pairing with strong input to induce LTP |
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Heterosynaptic LTP vs. homosynaptic LTP
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Heterosynaptic LTP involves many synapses and homosynaptic LTP involves a single synapse
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Experimental verification of LTP and LTD
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bidirectional plasticity in the visual cortex and hippocampus
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Mechanisms of long-term plasticity
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NMDAr can function as co-incidence detectors during LTP and LTD because they require both NT and depolarization
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Evidence for NMDAr involvement in induction of long-term plasticity
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APV (NMDAr antagonist) blocks LTP and calcium is necessary and sufficient for induction
Explains specificity (lack of glutamate at inactive synapses) and associativity (local depolarization allows activation of weaker synapses) |
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Expression and maintenance of LTP
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-CAMKII becomes constitutively active (autophosphorelation) upon calcium entry
-Direct upregulation of AMPAr response increasing conductance and receptor density -Requires transcriptional and translational changes to occur within the first two hours |
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Expression and maintenance of LTD
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Induction requires activation of NMDA receptors, increased intracellular calcium and activation of protein phosphatases
-Similar to LTP induction but occurs on a different timescale -Ultimately results in AMPAr internalization |
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Natural Hippocampal activity
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has a higher observed frequency of 30 Hz (about a third of experimental frequency) but is physiologically capable of inducing LTP
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Intrinsic properties
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Are dependent on the type of dendrite and derive from the diversity of ion channel density
Define the cell's excitability and spiking pattern |
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Changes in intrinsic properties
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-Increase the computational ability of the neuron
-Modulation through changing action potential threshold and synaptic relative weights |
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Backpropagation and synaptic plasticity
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-Mediated through active sodium channels (TTX reducible)
-Act as an integrative signal for spike-timing dependent synaptic plasticity |
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Spike timing dependent plasticity
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paired presynaptic spikes with induced postsynaptic spikes causes induction of LTP/LTD and depending on the timing of the spikes.
Magnitude and direction of synaptic change depend on timing between EPSP and back-propagating signal |
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EPSP spike timing and summation
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EPSP occurs before AP: LTD and supra linear summation
EPSP occurs after AP: LTP and sub-linear summation of transient calcium levels |
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Intrinsic excitability and EPSP
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Potentiation and depression are due in part to changes in intrinsic excitability
Short-term: neurotransmitter effects Rapid changes can be induced by LTP-like parameters dependent on NMDAr and calcium |
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Homoestatic plasticity
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Regulation of instrinsic excitability cultured in cortical neurons in order to stay within the specific range of activation
-cells that receive high frequency stimulation depress excitability -Firing rate is restored by regulation of currents -Synaptic scaling |
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Synaptic scaling
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Maintenance of relative weights of synapses but change in basal firing rate
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Maladaptive examples of plasticity
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Overcompensation of cells due to injection of pilcarpaine (muscarinic agonist) results in overly excitable cells and epilepsy
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Evidence that synaptic plasticity is involved in learning and memory
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-Lesion studies: hippocampal damage disturbs memory formation
-Synaptic plasticity occurs in vivo -LTP shares properties with learning and memory (experience dependent, rapid induction, input specific, associative) -Blocking synaptic plasticity inhibits learning -Genetic mutations that disrupt plasticity inhibit learning |
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CA1-NMDAr Knockout mice
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genetically engineered not to express NMDAr is the CA1 region of the hippocampus. Inhibits LTP specifically in the CA1 region demonstrating the necessity of NMDAr in LTP formation.
Morris Water Maze: demonstrates that memory is not restricted to the CA1 region |
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Lashley
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attempted to determine where the expression of memory occurs using lesion studies
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Equipotentiality
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all parts of the cortex contribute equally to memory and learning and one part can substitute for another.
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Mass action
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cortex works as a whole and performance improves when more of the cortex is involved
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Classical conditioning
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unconditioned stimulus becomes associated with conditioned stimulus that results in an unconditioned response
Ex. eye-blink conditioning in rodents (known to involve the cerebellum |
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Properties of the cerebellum
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-operates by allowing only creation of excitatory currents
-has veto-power over all stimulus -major output regions are deep cerebellar nuclei which activate motor commands -Excitation received from mossy fibers (strong synapse) and inhibition received from purkinje cells (weaker, indirect synapse) |
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Response of cerebellum to mossy fibers and purkinje cells
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-Mossy/climbing fibers have a strong synapse and an all-or-nothing response
-Purkinje cells have a weaker synapse and linearly increasing response to stimulus |
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Relevance of the cerebellum on associative learning and memory
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LTD occurs in the purkinje cell pathway, creating less inhibition allowing for the execution of motor commands.
Mechanism and cell properties are unique to cerebellum. Damage does not inhibit motor action but inhibits further associative learning. |
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Classical conditioning substitution in cerebellar pathway
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US: can be replaced by climbing fiber stimulation
CS: can be replaced by mossy fiber stimulation (resulting in LTD at the granule-purkinje cell pathway) |
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Properties of In Vivo pukinje cells
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-LTD is synapse specific
-PKC is necessary for LTD expression though deficiency does not completely eliminate associative learning b/c PKC mediates more types of memory storage and plasticity. |
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Inhibitory avoidance learning
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-Strong increase in phosphorylation of S831 (by CAMKII) on NMDAr causing increased AMPAr expression.
-Causes enhancement of EPSP fields in some CA1 hippocampal cells -(LTP occludes later LTP due saturation) |
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Ethology
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study of broad behaviors that repeat across a population when presented with appropriate stimulus
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Fixed Action pattern
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Definition: fixed pattern of behavior that is automatic, not goal oriented, repeats endless and completes the motion
Ex. egg rolling in birds, vomiting and sneezing in humans Decrease in frequency with increasing cognitive power |
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Triggering stimulus definition and properties
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stimulus that initiates a fixed action pattern
-Range of stimulus efficacy -No upper limit to trigger stimulus (supernormal stimuli) |
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Social behavior
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social language rests on stereotypical postures and calls
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methodology of study of neurobiological basis of behavior
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correlation, sufficiency and necessity
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Rationale for animal models
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-Diversity of organisms allow for the formation of neurological laws
-Simplicity of neurocircuitry: neurons maintain positions across individuals -Convenience (ex. jamming avoidance response in gymnarchus) |
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Stimulus of fast escape response in fish
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Vibrations hitting hair cells in the lateral line of activation activate neurons on the 8th cranial nerve
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M-cells
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specialized to detect activation of 8th cranial nerve using electrical signals and activate contralateral motor neurons and inhibit ipsilateral neurons via interneurons.
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Feedback inhibition in fast escape response
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collateral interneurons project back from m-cells to inhibit sequential firing via chemical and electrical means
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Feedforward inhibition in fast escape response
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PHP cells are also activated by 8th cranial nerve and inhibit both m-cells. Contralateral inhibition prevents simultaneous firing and ipsilateral inhibition is thought to establish a threshold.
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Axon cap
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-Provide a mechanism for fast inhibition
-Mediated through gap junctions with high extracellular resistance -Depolarizing current diffuses into the m-cell but the current loop is closed by the PHP cell drawing from the m-cell |
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PHP cells
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Passive Hyperpolarizing Potential cells
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Pre-pulse inhibition and startle response
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PPI is less prevalent in humans with neurological disorders meaning that drugs that treat neurological disorders targeting dopamine could restore PPI
Potential screening method for drugs: monitor the effects of the drug on fish with deficient PPI. |
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Chemoaffinity hypothesis vs. correlation change
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Hebb: external stimulus shapes the brain through plasticity
Sperry: Function follows form during development |
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Evidence for chemoaffinity hypothesis
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-Intense specificity of retinal projections
-Abalation experiments prediction of diffusible guiding factor -Stripe assay: nasal axons grow through anterior and posterior membranes but temporal axons only grow through anterior membranes -Ephrins and Eph Receptors gradient expression |
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Evidence for correlation change
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-Rewiring of cortex results in functional changes
-Geniculocortico input segregate into ocular dominance columns after onset of neural activity (and spontaneous retinal waves driving patterned activity) -Neural activity modifies axonal projections (Hebbian and binocular competition banding) -Dendritic growth requires neural activity and is enhanced by visual stimulation -LTP "activates" immature synapses with high NMDA/AMPA receptor ratios |
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Neural activity and gene regulation
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Cpg15 is a candidate gene for neural plasticity. It is activated during development and regulates synaptic maturation.
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Conclusions of chemoaffinity vs. correlation change
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molecular cues can specify rough wiring and create permissive environments but neural activity can further refine connections through Hebbian modulation and regulated gene expression
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Electrical synapses
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involve the flow of current between neurons that are physically connected to each other via gap junctions
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Properties of gap junctions (general)
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-Found all over the body in a diversity of tissues
-Necessary even in the oocyte -Bidirectional -Passive -Faster and simpler than chemical synapses |
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Common functions of gap junctions
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-Electrical conduction
-Sharing of metabolic or signaling molecules -Coordination of cell development -Synchronization of cellular activity -Cell adhesion -Suppression of mutation effects (via enzyme sharing) |
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Gap junction structure
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Consist of densely packed massive proteins that span the two cellular membranes. Each cell contributes a hemichannel or connexon. Connexons have 6 protein subunits called connexins. Connexins have 4 transmembrane segments with intracellular N/C tails. Contain gating structures.
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Properties of connexins
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Determine affinity to other hemichannels (via extracellular loops) and ion specificity
Specific (with over 20 genes that can be heteromeric or homomeric) Do not form covalent bonds |
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Gap junction lifecycle
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Synthesized in the ER, assembled in the golgi and transported to the membrane. Not much is known about the lifecycle of the hemichannel though they are typically closed to maintain membrane potentials. High turn over rate.
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Gap junction evolution
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Must have occurred early on in multicellular development b/c main classes of gap junction proteins (connexins, pannexins and innexins) have different genes sequences but nearly identical folding patterns
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Gap junction physiology
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-Often represented as resistors (highest conductance at largest magnitude of voltage difference across the cells)
-Typically symmetrical and bidirectional though voltage change is smaller in the second cell -Hyperpolarization of one causes hyperpolarization of the other -Important in escape mechanism of crayfish |
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Functions of the electrical synapse
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-Common in retina (making amacrine visualization difficult), specifically coded for by Cx36 gene
-Used by support cells in brain tissue (smaller, different connexins) -Inhibition in the cortex -Invertebrate circuitry: especially motor |
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Cx36 KO mice
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exhibit multiple deficits including visual, motor and memory deficits. Also abnormal EEG patterning and circadian behavior.
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Pharmacology of gap junctions
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Most gap junction antagonists lack potency and specificity however mefloquine (a derivative of quinine), an anti-malarial drug, is an effective Cx36 blocker causing some crazy dreams as a side-effect.
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