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512 Cards in this Set
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Chapter 6
Neurotransmitter systems |
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Three classes of neurotransmitters
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Amino acids, amines, and peptides
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Defining particular transmitter systems
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What the neurotransmitter does: synthetic machinery, packaging,
reuptake and degradation, etc. |
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Acetylcholine (Ach)
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– First identified neurotransmitter
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Nomenclature (-ergic)
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– Cholinergic, noradrenergic, GABAergic, et
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Neurotransmitter - three criteria to be considered a neurotransmitter
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1.Synthesis and storage in presynaptic neuron
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Neurotransmitter - three criteria to be considered a neurotransmitter
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2.Released by presynaptic axon terminal
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Neurotransmitter - three criteria to be considered a neurotransmitter
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3.Produces response in postsynaptic cell
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• Mimics response produced by release of
neurotransmitter from the presynaptic neuron |
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Studying Transmitter Localization
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Transmitters and Transmitter-
Synthesizing Enzymes |
Immunocytochemistry – localize molecules to cells
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Studying Transmitter Localization
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Look at figure on page 136
to understand immunocytochemistry |
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Studying Transmitter Localization
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In situ hybridization
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Localize synthesis of
protein or peptide to a cell (detect mRNA) -Look at figure on page 137 |
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Studying Transmitter Release
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Transmitter candidate: Synthesized and
localized in terminal and released upon stimulation |
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Studying Transmitter Release
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CNS contains a diverse mixture of synapses
that use different neurotransmitters |
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Studying Transmitter Release
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Brain slice as a model
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Kept alive in vitro(made to occur in a laboratory vessel) --> Stimulate synapses,
collect and measure released chemicals |
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Studying Synaptic Mimicry
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Qualifying condition: Molecules evoking same
response as neurotransmitters |
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Studying Synaptic Mimicry
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Microionophoresis: Looks at the postsynaptic actions to see if the molecule is a neurotransmitter because it must evoke the same response as a neurotransmitter
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Studying Synaptic Mimicry
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Molecular uncaging through UV photolysis. Laser
Uncaging is temporally and spatially precise method of releasing active neurotransmitter. |
1. Biological material is flooded with inactive “caged”
neurotransmitter |
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Studying Synaptic Mimicry
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Molecular uncaging through UV photolysis. Laser
Uncaging is temporally and spatially precise method of releasing active neurotransmitter. |
2. Focused laser cleaves a bond between the
transmitter and a cage. |
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Studying Synaptic Mimicry
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Microelectrode: Measures effects on membrane potential
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Studying Receptors
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Neuropharmacology
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Agonists (a chemical that binds to a receptor of a cell and triggers a response by that cell) and
antagonists (a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses) |
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Studying Receptors
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Neuropharmacology
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E.g., ACh receptors
– Nicotinic, Muscarinic |
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Studying Receptors
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Neuropharmacology
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Glutamate receptors
– AMPA, NMDA, and kainite |
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Studying Receptors
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Neuropharmacology
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Look at figure on page 139
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Studying Receptors
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Ligand-binding methods
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• Identify natural receptors using radioactive ligands
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Studying Receptors
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Ligand-binding methods
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• Can be: Agonist, antagonist, or chemical neurotransmitter
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Studying Receptors
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Ligand-binding methods
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Look at figure on page 140
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Studying Receptors
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Molecular analysis- receptor protein classes
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Transmitter-gated ion channels
» GABA receptors |
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Studying Receptors
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Molecular analysis- receptor protein classes
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Transmitter-gated ion channels
-5 subunits, each made with 6 different subunit polypeptides |
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Studying Receptors
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Molecular analysis- receptor protein classes
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G-protein-coupled receptors
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Evolution of neurotransmitters
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Neurotransmitter molecules
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Amino acids, amines, and peptides
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Dale’s Principle
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One neuron, one neurotransmitter
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Co-transmitters
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Two or more transmitters released from one nerve terminal
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Co-transmitters
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An amino acid or amine plus a peptide
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Look at figure on page 142
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Catecholaminergic Neurons
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Involved in movement, mood,
attention, and visceral function |
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Catecholaminergic Neurons
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Tyrosine: Precursor for three amine
neurotransmitters that contain catechol group |
• Dopamine (DA)
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Catecholaminergic Neurons
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Tyrosine: Precursor for three amine
neurotransmitters that contain catechol group |
• Norepinephrine (NE)
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Catecholaminergic Neurons
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Tyrosine: Precursor for three amine
neurotransmitters that contain catechol group -These three are also known as adrenaline |
• Epinephrine (E, adrenaline)
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Catecholaminergic Neurons
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Look at figure on page 143
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Serotonergic Neurons
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Amine neurotransmitter
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serotonin (5-HT) derived from tryptophan
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Serotonergic Neurons
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Regulates mood, emotional behavior, sleep
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Serotonergic Neurons
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Synthesis of serotonin
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Tryptophan hydroxylase: Converts tryptophan into 5-
HTP |
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Serotonergic Neurons
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Synthesis of serotonin
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5-HTP decarboxylase: Converts 5-HTP to 5-HT
Look at figure on page 147 |
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Serotonergic Neurons
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Selective serotonin reuptake
inhibitors (SSRIs) |
•Antidepressants
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Amino Acidergic Neurons
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Amino acid neurotransmitters:
Glutamate, glycine, gammaaminobutyric acid (GABA) |
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Amino Acidergic Neurons
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Differences among amino acidergic
neurons quantitative NOT qualitative |
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Amino Acidergic Neurons
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Glutamic acid decarboxylase (GAD)
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• Key enzyme in GABA synthesis
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Amino Acidergic Neurons
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Glutamic acid decarboxylase (GAD)
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• Good marker for GABAergic
neurons |
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Amino Acidergic Neurons
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Glutamic acid decarboxylase (GAD)
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• GABAergic neurons is important in
synaptic inhibition in the CNS |
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Amino Acidergic Neurons
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Look at figure on page 147
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Retrograte signaling with
endocanabinoids |
- can be released from “post” to “presynaptic” thats why its called retrograte signaling.
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Retrograte signaling with
endocanabinoids |
– CB1 receptors (G-coupled
receptors) are on presynaptic terminals |
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Retrograte signaling with
endocanabinoids |
Cannabis sativa = hemp used
for making rope but also for marijuana or hashish |
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Retrograte signaling with
endocanabinoids |
– from “post” to “pre”
– CB1 receptors (G-coupled receptors) are on presynaptic terminals – Cannabis sativa = hemp used for making rope but also for marijuana or hashish – Cannabis psychoactive properties known for 4000 years |
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Retrograte signaling with
endocanabinoids |
– At low doses, cannabis can
cause euphoria, feeling of relaxation and reduced pain. |
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Retrograte signaling with
endocanabinoids |
– At high doses, cannabis can
cause hallucinations or personality changes. |
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Retrograte signaling with
endocanabinoids |
Look at figure on page 148
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Transmitter-Gated Channels
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Introduction
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– Fast synaptic transmission
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Transmitter-Gated Channels
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Introduction
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– Sensitive detectors of chemicals and voltage
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Transmitter-Gated Channels
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Introduction
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– Regulate flow of large currents
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Transmitter-Gated Channels
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Introduction
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– Differentiates between similar ions
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Transmitter-Gated Channels
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The Basic Structure of Transmitter-Gated
Channels |
– Pentamer: Five protein subunits
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Transmitter-Gated Channels
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The Basic Structure of Transmitter-Gated
Channels |
Look at figure on page 155
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Transmitter-Gated Channels
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The Basic Structure of Transmitter-Gated
Channels |
Look at figure on page 157
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Amino Acid-Gated Channels
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GABA-Gated and Glycine-Gated Channels
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• GABA mediates inhibitory transmission
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Amino Acid-Gated Channels
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GABA-Gated and Glycine-Gated Channels
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• Glycine mediates non-GABA inhibitory transmission
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Amino Acid-Gated Channels
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GABA-Gated and Glycine-Gated Channels
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• Bind ethanol, benzodiazepines, barbiturates
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G-Protein-Coupled Receptors and Effectors
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Three steps for transmission
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Binding of the neurotransmitter to the receptor protein
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G-Protein-Coupled Receptors and Effectors
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Three steps for transmission
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Activation of G-proteins
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G-Protein-Coupled Receptors and Effectors
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Three steps for transmission
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Activation of effector systems
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G-Protein-Coupled Receptors and Effectors
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The Basic Structure of G-Protein-Coupled
Receptors (GPCRs) |
Single polypeptide with seven membranespanning alpha-helices
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G-Protein-Coupled Receptors and Effectors
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The Ubiquitous G-Proteins
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– GTP-binding (G-protein)
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G-Protein-Coupled Receptors and Effectors
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The Ubiquitous G-Proteins
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– Signal--> from receptor to effector proteins
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G-Protein-Coupled Receptors
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The Ubiquitous G-Proteins
-Five steps in G-protein operation |
(1) Inactive: Three subunits - α,
β, and γ - “float” in membrane (α bound to GDP) |
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G-Protein-Coupled Receptors
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The Ubiquitous G-Proteins
-Five steps in G-protein operation |
(2) Active: Bumps into activated
receptor and exchanges GDP for GTP |
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G-Protein-Coupled Receptors
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The Ubiquitous G-Proteins
-Five steps in G-protein operation |
(3) Gα-GTP and Gβγ - Influence
effector proteins |
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G-Protein-Coupled Receptors
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The Ubiquitous G-Proteins
-Five steps in G-protein operation |
(4) Gα inactivates by slowly
converting GTP to GDP |
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G-Protein-Coupled Receptors
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The Ubiquitous G-Proteins
-Five steps in G-protein operation |
(5) Gβγ recombine with Gα-GDP
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G-Protein-Coupled Receptors
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The Ubiquitous G-Proteins
-Five steps in G-protein operation |
Look at figure on page 159
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G-Protein-Coupled Receptors and Effectors
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GPCR (G-Protein-Coupled Receptors) Effector Systems
– The Shortcut Pathway |
From receptor to Gprotein
to ion channel |
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G-Protein-Coupled Receptors and Effectors
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GPCR Effector Systems
– The Shortcut Pathway |
Fast and local
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G-Protein-Coupled Receptors and Effectors
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GPCR Effector Systems
– The Shortcut Pathway |
Look at figure on page 160
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G-Protein-Coupled Receptors and Effectors
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GPCR Effector Systems
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Second Messenger Cascades
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G-Protein-Coupled Receptors and Effectors
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G-protein: Couples neurotransmitter with
downstream enzyme activation |
E.g., G-protein activates AC--> generates cAMP-->
activates PKA (effector protein) |
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G-Protein-Coupled Receptors and Effectors
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Look at page 161
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GPCR Effector Systems
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Push-pull method
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G_i (inhibitory G-Protein) inhibits AC (adenylyl cyclase)
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GPCR Effector Systems
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Push-pull method
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G_s (stimulatory G-protein) stimulates AC (adenylyl cyclase)
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GPCR Effector Systems
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Push-pull method
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Look at page at figure on page 161
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G-Protein-Coupled Receptors and Effectors
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GPCR Effector Systems (Cont’d)
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– Phosphorylation and Dephosphorylation
• Phosphate groups added to or removed from a protein – Changes conformation and biological activity |
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G-Protein-Coupled Receptors and Effectors
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The Function of Signal Cascades
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Signal amplification by GPCRs
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G-Protein-Coupled Receptors and Effectors
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Look at figure on page 163
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Divergence and Convergence
in Neurotransmitter Systems |
Divergence
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One transmitter
activates more than one receptor subtype--> greater postsynaptic response |
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Divergence and Convergence
in Neurotransmitter Systems |
Convergence
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Different transmitters
converge to affect same effector system |
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Divergence and Convergence
in Neurotransmitter Systems |
Look at figure on page 165
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Anatomy and Functions
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Different structure and function, common principles
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• Small set of neurons at core
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The Diffuse Modulatory Systems of the Brain
Anatomy and Functions |
Different structure and function, common principles
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• Arise from central core of brain
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Anatomy and Functions
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Different structure and function, common principles
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• One neuron influences others
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Anatomy and Functions
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Different structure and function, common principles
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• Synapses release transmitter molecules into
extracellular fluid |
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The Diffuse Modulatory Systems of the Brain
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The Nonadrenergic Locus Coeruleus (LC)
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Path: Axons innervate cerebral cortex, thalamus,
hypothalamus, olfactory bulb, cerebellum, midbrain, spinal cord |
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The Diffuse Modulatory Systems of the Brain
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The Nonadrenergic Locus Coeruleus (LC)
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Function: Regulation of attention, arousal, sleepwake
cycles, learning and memory, anxiety and pain, mood, brain metabolism |
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The Diffuse Modulatory Systems of the Brain
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The Nonadrenergic Locus Coeruleus (LC)
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Activation: New, unexpected, nonpainful sensory stimuli
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The Diffuse Modulatory Systems of the Brain
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The Nonadrenergic Locus Coeruleus (LC)
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Look at figure on page 500
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The Diffuse Modulatory
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The Nonadrenergic Locus Coeruleus (LC)
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The Diffuse Modulatory
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9 Raphe Nuclei in brain stem
-serotonin containing neurons are mostly clustered within the 9 raphe nuclei |
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The Diffuse Modulatory
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Controls:
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- sleep-wake cycle
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The Diffuse Modulatory
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Controls:
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- mood control
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The Diffuse Modulatory
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Controls:
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- emotion
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The Diffuse Modulatory
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Depression
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Look at figure on page 501
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The Diffuse Modulatory
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Both locus coeruleus and the raphe nuclei are part of
the ascending reticular activating system: |
“core” of the brain stem is involved in processes that arouse the forebrain
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The Diffuse Modulatory Systems of the Brain
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Dopaminergic Cells in midbrain:
-Substantia Nigra |
Dopaminergic
projection to the striatum |
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The Diffuse Modulatory Systems of the Brain
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Dopaminergic Cells in midbrain:
-Substantia Nigra |
Facilitates the
initiation of voluntary movements |
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The Diffuse Modulatory Systems of the Brain
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Dopaminergic Cells in midbrain:
-Substantia Nigra |
Parkinson’s Disease
(motor disorders) |
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The Diffuse Modulatory Systems of the Brain
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Dopaminergic Cells in midbrain:
-Ventral tegmental area (VTA) |
• Mesocorticolimbic
dopamine System |
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The Diffuse Modulatory Systems of the Brain
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Dopaminergic Cells in midbrain:
-Ventral tegmental area (VTA) |
• innervates limbic and
frontal cortical regions |
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The Diffuse Modulatory Systems of the Brain
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Dopaminergic Cells in midbrain:
-Ventral tegmental area (VTA) |
• “reward” system
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The Diffuse Modulatory Systems of the Brain
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Dopaminergic Cells in midbrain:
-Ventral tegmental area (VTA) |
• Psychiatric disorders
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The Diffuse Modulatory Systems of the Brain
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Look at figure on page 503
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Cholinergic Systems
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Basal forebrain complex
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Core of
telencephalon, medial and ventral to basal ganglia |
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Cholinergic Systems
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Basal forebrain complex
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Function: Unknown,
participates in learning and memory |
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Cholinergic Systems
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Pontomesencephalotegmental
complex |
• Releases ACh
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Cholinergic Systems
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Pontomesencephalotegmental
complex |
• Function: Regulates
excitability of thalamic sensory relay nuclei |
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Cholinergic Systems
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Look at figure on page 504
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Drugs and the Diffuse Modulatory
Systems |
Psychoactive drugs: Act on CNS
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Drugs and the Diffuse Modulatory
Systems |
Many drugs of abuse act on modulatory
systems |
• Noradrenergic
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Drugs and the Diffuse Modulatory
Systems |
Many drugs of abuse act on modulatory
systems |
• Dopaminergic
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Drugs and the Diffuse Modulatory
Systems |
Many drugs of abuse act on modulatory
systems |
• Serotonergic
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Hallucinogens
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LSD discovery: Accidentally by Swiss chemist Albert Hofmann
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Hallucinogens
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LSD chemical structure: Close to
serotonin, potent agonist |
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Hallucinogens
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Effect: Dreamlike state, mixing of
perceptions – cortical areas |
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Stimulants
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Look at figure on page 506
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Concluding remarks
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Neurotransmitters
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– Transmit information between neurons
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Neurotransmitters
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– Essential link between neurons and effector cell
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Signaling pathways
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Signaling network within a neuron somewhat resembles
brain’s neural network |
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Signaling pathways
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Inputs vary temporally and spatially to increase and/or
decrease drive |
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Signaling pathways
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Delicately balanced
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Signaling pathways
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Signals regulate signals- drugs can shift the balance of
signaling power |
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Diffuse modulatory systems (all over the brain)
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Some neurotransmitter systems have great reach of their
influences |
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Diffuse modulatory systems (all over the brain)
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Detailed level - Each system performs different functions
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Diffuse modulatory systems (all over the brain)
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General level - All work to maintain brain homeostasis
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Diffuse modulatory systems (all over the brain)
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Some drugs affect the diffuse modulatory systems
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Lecture 14:
The Emotional Brain Chapter 18 |
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Significance of Emotions
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Emotional experience; Emotional expression
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Significance of Emotions
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Human brain imaging techniques
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• Renaissance in the study of emotion
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Significance of Emotions
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Affective neuroscience
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• Neural basis of emotion and mood
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Significance of Emotions
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Mood
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• Emotion extended in time
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What Is Emotion?
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Theories of Emotion
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The James-Lange Theory
• Experience emotion – Response to physiological changes in the body |
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What Is Emotion?
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Theories of Emotion
– The Cannon-Bard Theory |
Thalamus—Key role in emotional sensations
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What Is Emotion?
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Theories of Emotion
– The Cannon-Bard Theory |
Look at figure on page 566
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What Is Emotion?
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Unconscious Emotions
-Sensory input: Emotional impact |
Without conscious awareness of stimuli
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What Is Emotion?
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Unconscious Emotions
-Sensory input: Emotional impact |
Rules out theories of emotion
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What Is Emotion?
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Unconscious Emotions
-Many ways to process emotional information |
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The Limbic System Concept
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Broca’s Limbic Lobe
-Group of cortical areas |
Forms a ring around brain stem
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The Limbic System Concept
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Look at figure on page 569
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The Limbic System Concept
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The Papez Circuit
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Emotional system on the medial wall of the brain
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The Limbic System Concept
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The Papez Circuit
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Links cortex with hypothalamus
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The Limbic System Concept
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Look at figure on page 569
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The Limbic System Concept
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The Papez Circuit
-Hippocampus: Emotion |
Rabies infection:
– Evidence of infection; Hyperemotional responses |
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The Limbic System Concept
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Role of anterior thalamus in emotion
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Lesions led to emotional disorder
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The Limbic System Concept
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Limbic system- interconnected structures around
the brain stem |
Together, thought to govern sensation and emotional
expression |
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The Limbic System Concept
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Difficulties with the Single Emotion
System Concept |
-- Diverse emotions experienced
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The Limbic System Concept
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Difficulties with the Single Emotion
System Concept |
– Structures involved in emotion
• No one-to-one relationship between structure and function |
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The Limbic System Concept
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Difficulties with the Single Emotion
System Concept |
– Limbic system: Utility of single, discrete
emotion system questionable |
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The Limbic System Concept
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The Klüver-Bucy Syndrome
– Klüver and Bucy |
Temporal lobectomy in rhesus monkeys
– Decreased fear and aggression |
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The Limbic System Concept
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The Klüver-Bucy Syndrome
– Klüver and Bucy |
Temporal lobectomy in rhesus monkeys
– Decreased vocalizations and facial expressions |
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The Limbic System Concept
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The Klüver-Bucy Syndrome
– Temporal lobectomy in humans |
Exhibit symptoms of Klüver-Bucy syndrome
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The Limbic System Concept
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The Klüver-Bucy Syndrome
– Temporal lobectomy in humans |
Flattened emotions
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The Amygdala and Associated
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Anatomy of the Amygdala
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Look at figure on page 573
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The Amygdala and Associated
Brain Circuits |
The Amygdala and Fear
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Bilateral amygdalectomy in
animals—reduce fear and aggression |
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The Amygdala and Associated
Brain Circuits |
The Amygdala and Fear
-Range of effects of amygdala lesions |
Fear, anger, sadness, and disgust
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The Amygdala and Associated
Brain Circuits |
The Amygdala and Fear
-Range of effects of amygdala lesions |
S.M. case study
– Inability to recognize fear in facial expressions |
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The Amygdala and Associated
Brain Circuits |
The Amygdala and Fear
-Electrical stimulation of amygdala |
Increased vigilance or attention
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The Amygdala and Associated
Brain Circuits |
A Neural Circuit for Learned Fear
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fMRI images and PET imaging: Confirm the role
of amygdala in emotion |
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The Amygdala and Associated
Brain Circuits |
Look at figure on page 575
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The Amygdala and Associated
Brain Circuits |
The Amygdala and Aggression
– Predatory Aggression—Attacks |
Against different species for food
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The Amygdala and Associated
Brain Circuits |
The Amygdala and Aggression
– Predatory Aggression—Attacks |
Few vocalizations; Attack head or neck
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The Amygdala and Associated
Brain Circuits |
The Amygdala and Aggression
– Predatory Aggression—Attacks |
No activity in sympathetic division of ANS
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The Amygdala and Associated
Brain Circuits |
The Amygdala and Aggression
-- Affective aggression |
Used for show, not kill for food
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The Amygdala and Associated
Brain Circuits |
The Amygdala and Aggression
-- Affective aggression |
High levels of sympathetic activity
|
|
|
The Amygdala and Associated
Brain Circuits |
The Amygdala and Aggression
-- Affective aggression |
Makes vocalizations; Threatening posture
|
|
|
The Amygdala and Associated
Brain Circuits |
The Amygdala and Aggression (Cont’d)
– Surgery to Reduce Human Aggression |
• Amygdalactomy
|
|
|
The Amygdala and Associated
Brain Circuits |
The Amygdala and Aggression (Cont’d)
– Surgery to Reduce Human Aggression |
• Psychosurgery – last resort
|
|
|
The Amygdala and Associated
Brain Circuits |
The Amygdala and Aggression (Cont’d)
-- Symptoms |
• Reduced aggressive asocial behavior
|
|
|
The Amygdala and Associated
Brain Circuits |
The Amygdala and Aggression (Cont’d)
-- Symptoms |
• Increased ability to concentrate
|
|
|
The Amygdala and Associated
Brain Circuits |
The Amygdala and Aggression (Cont’d)
-- Symptoms |
• Decreased hyperactivity
|
|
|
Neural Components of
Aggression Beyond the Amygdala |
The Hypothalamus and
Aggression – Removal of cerebral hemispheres |
Sham rage- Aggression from little provocation, getting made for no reason.
|
|
|
Neural Components of
Aggression Beyond the Amygdala |
The Hypothalamus and
Aggression – Removal of cerebral hemispheres |
Behavior reversed by small
lesions in hypothalamus |
|
|
Neural Components of
Aggression Beyond the Amygdala |
The Hypothalamus and
Aggression – Removal of cerebral hemispheres |
Specific lesions, posterior
hypothalamus in fear, aggression behaviors |
|
|
Neural Components of
Aggression Beyond the Amygdala |
The Hypothalamus and
Aggression – Removal of cerebral hemispheres |
Look at figure on page 579
|
|
|
Neural Components of
Aggression Beyond the Amygdala |
The Hypothalamus and
Aggression (Cont’d) – Electrical stimulation |
• Hess, 1920s
– Varying effects with varied intensities |
|
|
Neural Components of
Aggression Beyond the Amygdala |
The Hypothalamus and
Aggression (Cont’d) – Electrical stimulation |
• Flynn, 1960s
– Elicited affective and predatory aggressions |
|
|
Neural Components of
Aggression Beyond the Amygdala |
The Hypothalamus and
Aggression (Cont’d) – Electrical stimulation |
|
|
|
Neural Components of
Aggression Beyond the Amygdala |
The Midbrain and Aggression
--Two pathways |
Hypothalamus sends signals to brain stem by Medial forebrain bundle
|
|
|
Neural Components of
Aggression Beyond the Amygdala |
The Midbrain and Aggression
--Two pathways |
Hypothalamus sends signals to brain stem by Dorsal longitudinal fasciculus
|
|
|
Neural Components of
Aggression Beyond the Amygdala |
The Midbrain and Aggression
--Two pathways |
Look at figure on page 581
|
|
|
Serotonin and Aggression
|
Neurotransmitter Serotonin
|
– Regulating aggression
|
|
|
Serotonin and Aggression
|
Neurotransmitter Serotonin
|
– Raphe nuclei of brain stem
|
|
|
Serotonin and Aggression
|
Neurotransmitter Serotonin
|
– Experiments
• Induced aggression in rodents |
|
|
Serotonin and Aggression
|
Neurotransmitter Serotonin
|
– Drug PCPA
• Blocks serotonin synthesis |
|
|
Serotonin and Aggression
|
Neurotransmitter Serotonin
|
Look at figure on page 501
|
|
|
Serotonin and Aggression
|
Serotonin Receptor Knockout Mice
|
14 serotonin receptor subtypes
|
|
|
Serotonin and Aggression
|
Serotonin Receptor Knockout Mice
|
Knockout Mice (recombinant DNA
techniques) |
|
|
Serotonin and Aggression
|
Serotonin Receptor Knockout Mice
|
5-HT1A and 5-HT1B
|
|
|
Serotonin and Aggression
|
Serotonin Receptor Knockout Mice
|
High concentrations in raphe nuclei
|
|
|
Serotonin and Aggression
|
Serotonin Receptor Knockout Mice
|
5-HT1A and 5-HT1B autoreceptors—global
regulatory role |
|
|
Serotonin and Aggression
|
Serotonin Receptor Knockout Mice
|
Agonists: Decrease anxiety, aggressiveness
|
|
|
Concluding Remarks
|
..
|
|
|
|
Neural Pathways
|
Involved in the experience, expression of emotion
|
• Involves widespread activity in the nervous system
|
|
|
Emotional Reactions
|
• Result of interactions between sensory stimuli
|
|
|
|
Emotional Reactions
|
• Brain circuitry; Past experiences;
Neurotransmitter systems |
|
|
|
Lecture 15:
The Neuroscience of Language Chapter 20 |
..
|
|
|
|
Language
|
– System by which sounds, symbols, and gestures
used for communication |
|
|
|
Language
|
– Process
|
• Language comes into brain through visual and auditory
systems |
|
|
Language
|
– Process
|
• Motor system: Produces speech, writing
|
|
|
Language
|
– Process
|
• Processing between sensory and motor systems; Essence
of language |
|
|
The Discovery of Specialized Language Areas
in the Brain |
Aphasia
|
Partial/complete loss of language abilities following brain damage
|
|
|
The Discovery of Specialized Language Areas
in the Brain |
Aphasia
|
Greek/Roman Empires thought that the Tongue controls speech
|
|
|
The Discovery of Specialized Language Areas
in the Brain |
Aphasia
|
Sixteenth century: Speech impairment, tongue
not affected |
|
|
The Discovery of Specialized Language Areas
in the Brain |
Aphasia
|
1770: Johann Gesner, brain damage
|
|
|
The Discovery of Specialized Language Areas
in the Brain |
Aphasia
|
1825: Jean-Baptist Bouillard, frontal lobes
|
|
|
The Discovery of Specialized Language Areas
in the Brain |
Aphasia
|
1861: Cortical area in frontal lobe
|
|
|
The Discovery of Specialized Language Areas
in the Brain |
Broca’s area
|
• Paul Broca in 1864: Region of dominant left frontal
lobe, articulate speech |
|
|
The Discovery of Specialized Language Areas
in the Brain |
Broca’s area
|
– Dominant: Heavily involved in particular task
|
|
|
The Discovery of Specialized Language Areas
in the Brain |
Broca’s area
|
--Wada procedure: Anesthetize single hemisphere
|
|
|
The Discovery of Specialized Language Areas
in the Brain |
Look at figure on page 620
|
|
|
|
The Discovery of Specialized Language Areas in the Brain.
|
Wernicke’s area
|
• Karl Wernicke in 1874: Superior surface of
temporal lobe between auditory cortex and angular gyrus, lesions disrupt normal speech |
|
|
The Discovery of Specialized Language Areas in the Brain.
|
Studying the relationship between
language and the brain |
– Correlate functional deficits with lesions
|
|
|
The Discovery of Specialized Language Areas in the Brain.
|
Types of Aphasia
– Broca’s Aphasia (motor, nonfluent aphasia) |
• Difficulty speaking, but understand
spoken/heard language |
|
|
The Discovery of Specialized Language Areas in the Brain.
|
Types of Aphasia
– Broca’s Aphasia (motor, nonfluent aphasia) |
• Paraphasic errors
|
|
|
The Discovery of Specialized Language Areas in the Brain.
|
Types of Aphasia
– Broca’s Aphasia (motor, nonfluent aphasia) |
• Pause to search for words, repeat “overlearned” things, difficulty repeating words
|
|
|
Types of Aphasia
|
Wernicke’s aphasia
|
|
|
|
Types of Aphasia
|
Speech fluent, comprehension poor
|
|
|
|
Types of Aphasia
|
Howard Gardner case study
|
• Strange mixture of clarity and gibberish
|
|
|
Types of Aphasia
|
Howard Gardner case study
|
• Correct sounds, incorrect sequence
|
|
|
Types of Aphasia
|
Howard Gardner case study
|
• Comprehension difficult to assess
|
|
|
Types of Aphasia
|
Howard Gardner case study
|
• Playing music, writing similar
|
|
|
Types of Aphasia
|
Location of Wernicke’s area - clues
|
|
|
|
Wernicke’ Aphasia
|
– Storing memories of sounds that make up words
|
|
|
|
Wernicke’ Aphasia
|
– Symptoms: Mixture of clarity and gibberish,
undisturbed by sound of own or other’s speech |
|
|
|
Wernicke’ Aphasia
|
– Characteristics: Correct words in incorrect
sequence, incorrect word similar to correct word |
|
|
|
Aphasia and the
Wernicke-Geschwind Model |
– Broca’s area
|
|
|
|
Aphasia and the
Wernicke-Geschwind Model |
– Wernicke’s area
|
|
|
|
Aphasia and the
Wernicke-Geschwind Model |
– Arcuate Fasciculus
|
|
|
|
Aphasia and the
Wernicke-Geschwind Model |
– Angular gyrus
|
|
|
|
Aphasia and the
Wernicke-Geschwind Model |
– Problems with model
|
|
|
|
Aphasia and the
Wernicke-Geschwind Model |
Look at figure on page 625 & 626
|
|
|
|
Conduction Aphasia
|
– Lesion of fibers composing arcuate fasciculus
|
|
|
|
Conduction Aphasia
|
– Comparison with Broca’s aphasia, Wernicke’s
aphasia: Comprehension good, speech fluent |
|
|
|
Conduction Aphasia
|
– Difficulty repeating words
|
|
|
|
Conduction Aphasia
|
– Symptoms: Repetition substitutes/omits words,
paraphasic errors, cannot repeat function, nonsense words, polysyllabic words |
Look at table on page 622
|
|
|
Aphasia in Bilinguals and the Deaf
|
– Aphasia in bilinguals- Language affected depends
on: Order, fluency, use of language |
|
|
|
Aphasia in Bilinguals and the Deaf
|
– Sign language aphasias analagous to speech
aphasias --> but can be produced by lesions in slightly different locations |
|
|
|
Aphasia in Bilinguals and the Deaf
|
-- Verbal and sign language recovered together in
one case--> indicating overlapping regions used for both |
|
|
|
Aphasia in Bilinguals and the Deaf
|
– Evidence suggests some universality to language
processing in the brain |
|
|
|
Split-Brain Studies
|
Roger Sperry (Caltech; 1950s)
|
|
|
|
Split-Brain Studies
|
Split-brain procedure
|
• Sever axons making up the corpus callosum
|
|
|
Split-Brain Studies
|
Split-brain procedure
|
• No major deficits
|
|
|
Split-Brain Studies
|
Split-brain procedure
|
• With proper experiments, animals behaved as if
they had 2 brains |
|
|
Asymmetrical Language Processing in the
Cerebral Hemispheres |
Look at figure on page 628 & 629
|
|
|
|
Language Processing in Split-Brain Humans
|
– Gazzaniga: Stimuli to one hemisphere
|
|
|
|
Language Processing in Split-Brain Humans
|
– Observation: Two hemispheres initiated conflicting behaviors
|
Look at figure on page 630
|
|
|
Left Hemisphere Language Dominance
|
– Right visual field, repeated easily
|
|
|
|
Left Hemisphere Language Dominance
|
– Left visual field, difficulty verbalizing
|
|
|
|
Left Hemisphere Language Dominance
|
– Image only in left visual field, object in left
hand, unable to describe |
|
|
|
Left Hemisphere Language Dominance
|
– Split-brain
|
• Unable to describe anything to left of visual fixation point
|
|
|
Language Functions of the Right
Hemisphere |
– Functions of right hemisphere: Read and
understand numbers, letters, and short words (nonverbal response) |
|
|
|
Language Functions of the Right
Hemisphere |
– Baynes, Gazzaniga, and colleagues: Right
hemisphere able to write, cannot speak |
|
|
|
Language Functions of the Right
Hemisphere |
– Right hemisphere: Drawing, puzzles, sound
nuances |
|
|
|
Language Functions of the Right
Hemisphere |
– Left hemisphere: Language
|
|
|
|
Anatomical Asymmetry and Language
|
– Left lateral (Sylvian) fissure longer and less
steep than right |
|
|
|
Anatomical Asymmetry and Language
|
– Geschwind and Levitsky: Left planum temporal
larger than right in 65% cases |
|
|
|
Anatomical Asymmetry and Language
|
– Functional human asymmetry: More than 90%
humans right-handed |
|
|
|
Anatomical Asymmetry and Language
|
– Animals: Equal numbers of right-handers and
left-handers |
|
|
|
Anatomical Asymmetry and
Language |
– Left lateral (Sylvian) fissure
longer and less steep than right |
Look at figure on page 631
|
|
|
Anatomical Asymmetry and
Language |
– Geschwind and Levitsky: Left
planum temporal larger than right in 65% cases |
|
|
|
Anatomical Asymmetry and
Language |
– Functional human asymmetry:
More than 90% humans righthanded |
|
|
|
Anatomical Asymmetry and
Language |
– Animals: Equal numbers of righthanders
and left-handers |
|
|
|
Anatomical Asymmetry and
Language |
– Left lateral (Sylvian) fissure
longer and less steep than right |
|
|
|
Anatomical Asymmetry and
Language |
– Geschwind and Levitsky: Left
planum temporal larger than right in 65% cases |
|
|
|
Anatomical Asymmetry and
Language |
– Functional human asymmetry:
More than 90% humans righthanded |
|
|
|
Anatomical Asymmetry and
Language |
– Animals: Equal numbers of righthanders
and left-handers |
Look at figure on page 632
|
|
|
Language Studies Using Brain Stimulation and
Brain Imaging |
Language Studies
|
– Old methods: Correlate language deficits with
postmortem analysis of brain damage |
|
|
Language Studies Using Brain Stimulation and
Brain Imaging |
Language Studies
|
– Recent techniques
• Study language function in brains of living humans: Electrical brain stimulation and PET |
|
|
Language Studies Using Brain Stimulation and
Brain Imaging |
The Effects of Brain Stimulation on Language
|
– Three main effects: Vocalizations, speech arrest,
speech difficulties similar to aphasia |
|
|
The Effects of Brain Stimulation on
Language |
– Motor cortex: Immediate
speech arrest |
|
|
|
The Effects of Brain Stimulation on
Language |
– Broca’s area: Speech
stopped after strong stimulation, speech hesitation from weak stimulation |
|
|
|
The Effects of Brain Stimulation on
Language |
– Posterior parietal lobe
near Sylvian fissure and temporal lobe: Word confusion and speech arrest |
Look at figure on page 632
|
|
|
The Effects of Brain Stimulation on
Language |
– Motor cortex: Immediate
speech arrest |
|
|
|
The Effects of Brain Stimulation on
Language |
George Ojemann: Small
parts of cortex: naming, reading, repeating facial movements |
Look at figure on page 633
|
|
|
The Effects of Brain Stimulation on
Language |
– Broca’s area: Speech
stopped after strong stimulation, speech hesitation from weak stimulation |
|
|
|
The Effects of Brain Stimulation on
Language |
– Motor cortex: Immediate speech arrest
|
|
|
|
The Effects of Brain Stimulation on
Language |
– Posterior parietal lobe
near Sylvian fissure and temporal lobe: Word confusion and speech arrest |
Look at figure on page 632
|
|
|
The Effects of Brain Stimulation on
Language |
– Broca’s area: Speech stopped after strong
stimulation, speech hesitation from weak stimulation |
|
|
|
The Effects of Brain Stimulation on
Language |
George Ojemann: Small
parts of cortex: naming, reading, repeating facial movements |
Look at figure on page 633
|
|
|
The Effects of Brain Stimulation on
Language |
– Posterior parietal lobe near Sylvian fissure and
temporal lobe: Word confusion and speech arrest |
|
|
|
The Effects of Brain Stimulation on
Language |
– Motor cortex: Immediate speech arrest
|
|
|
|
The Effects of Brain Stimulation on
Language |
– George Ojemann: Small parts of cortex: naming, reading, repeating facial movements
|
|
|
|
The Effects of Brain Stimulation on
Language |
– Broca’s area: Speech stopped after strong
stimulation, speech hesitation from weak stimulation |
|
|
|
The Effects of Brain Stimulation on
Language |
– Posterior parietal lobe near Sylvian fissure and
temporal lobe: Word confusion and speech arrest |
|
|
|
The Effects of Brain Stimulation on
Language |
– George Ojemann: Small parts of cortex: naming, reading, repeating facial movements
|
|
|
|
Imaging of Language Processing in the Human Brain
|
fMRI (Lehericy and colleagues): Record
during 3 different language tasks |
– Activated brain areas consistent with temporal and
parietal language areas |
|
|
Imaging of Language Processing in the Human Brain
|
fMRI (Lehericy and colleagues): Record
during 3 different language tasks |
– More activity than expected in nondominant hemisphere
|
|
|
Imaging of Language Processing in the Human Brain
|
fMRI (Lehericy and colleagues): Record
during 3 different language tasks |
– Activated brain areas consistent with temporal and
parietal language areas |
|
|
Imaging of Language Processing in the Human Brain
|
PET: Compare sensory responses to words
vs. speech production |
Look at figure on page 627
|
|
|
Imaging of Language Processing in the Human Brain
|
fMRI (Lehericy and colleagues): Record
during 3 different language tasks |
– More activity than expected in nondominant hemisphere
|
|
|
Language Acquisition
|
Mechanism in infants
|
Syllable emphasis
|
|
|
Imaging of Language Processing in the Human Brain
|
PET: Compare sensory responses to words
vs. speech production |
Look at figure on page 627
|
|
|
Language Acquisition
|
Mechanism in infants
|
Motherese
– Adults talk to infants; Speech slower, exaggerated, vowel sounds clearly articulated |
|
|
Language Acquisition
|
Mechanism in infants
|
Syllable emphasis
|
|
|
Language Acquisition
|
Complexity: Foreign language
|
|
|
|
Language Acquisition
|
Mechanism in infants
|
Motherese
– Adults talk to infants; Speech slower, exaggerated, vowel sounds clearly articulated |
|
|
Language Acquisition
|
Dehaene-Lambertz: 3 month infant, brain response to spoken words similar to adults
|
|
|
|
Language Acquisition
|
Complexity: Foreign language
|
|
|
|
Language Acquisition
|
Dehaene-Lambertz: 3 month infant, brain response to spoken words similar to adults
|
|
|
|
Concluding Remarks
|
..
|
|
|
|
• Language processing
|
– Person repeats word read
|
|
|
|
• Initial activity in visual cortex, then activity in motor cortex corresponding to muscles
that move vocal apparatus |
.
|
|
|
|
• Multiple brain areas critical for language
|
.
|
|
|
|
- Language skills: Naming, articulation,
grammar usage, comprehension |
.
|
|
|
|
• Further brain imaging studies will reveal
more about language systems organization |
.
|
|
|
|
Lecture 16:
The Neuroscience of Learning & Memory Chapter 24 |
..
|
|
|
|
Neurobiology of memory
|
– Identifying where and how different types of
information are stored |
|
|
|
Hypothesis by Donald Hebb
|
– Memory results from synaptic alterations
|
|
|
|
Relationship between visual development and learning
|
– Similar mechanisms in different cortical areas
|
|
|
|
Memories range from stated facts to ingrained motor patterns
|
..
|
|
|
|
microangiopathic hemolytic anemia, acute renal failure, thrombocytopenia
|
Hemolytic Uremic Syndrome
-most a/w Shiga-toxin-producing organisms like E coli 0157:H7, Shigella dysenteriae Sx: anemia (pallor, weak, tachycardia), thrombocytopenia (petechiae, purpura), fever, abdominal pain, bloody diarrhea Labs: decr Hgb, decr Hct, decr RBC count, incr LDH, incr Reticulocytes, incr BT but other coag studies nrl, incr BUN, incr creatinine note: you will have low platelets...but just like with DIC and TTP: you will have thrombosis!!! also in Heparin induced thrombocytopenia, you become hypercoaguable.. |
|
|
|
Learning & Memory
|
Learning
|
– Acquisition of new information
|
|
|
Learning & Memory
|
Memory
|
– Retention of learned information
|
|
|
Learning & Memory
|
Learning
|
– Acquisition of new information
|
|
|
Learning & Memory
|
The way information is stored may change over time
|
|
|
|
Learning & Memory
|
Memory
|
– Retention of learned information
|
|
|
Learning & Memory
|
Declarative memory (explicit)
|
– Facts and events
|
|
|
Learning & Memory
|
The way information is stored may change over time
|
|
|
|
Learning & Memory
|
Nondeclarative memory (implicit)
|
– Procedural memory- skills, habits, behaviors
|
|
|
Learning & Memory
|
Declarative memory (explicit)
|
– Facts and events
|
|
|
Multiple brain systems for memory storage
|
Look at figure on page 727
|
|
|
|
Learning & Memory
|
Nondeclarative memory (implicit)
|
– Procedural memory- skills, habits, behaviors
|
|
|
Multiple brain systems for memory storage
|
Look at figure on page 727
|
|
|
|
Procedural Learning
|
Nonassociative Learning
– Habituation |
• Learning to ignore
stimulus that lacks meaning |
|
|
Procedural Learning
|
Nonassociative Learning
– Sensitization |
• Learning to intensify
response to stimuli |
|
|
Procedural Learning
|
Look at figure on lecture 16 slide 3
|
|
|
|
Procedural Learning
|
Associative Learning
|
– Classical Conditioning
-Look at figure on lecture 16 slide 4 |
|
|
Associative Learning
|
Classical Conditioning
|
• Associates a stimulus that evokes responseunconditional
stimulus with second stimulus that does not evoke response- conditional stimulus |
|
|
Associative Learning
|
Instrumental Conditioning
|
• Experiment by Edward Thorndike
|
|
|
Associative Learning
|
Instrumental Conditioning
|
• Complex neural circuits due to motivation
|
|
|
Types of Memory and Amnesia
|
Long-Term, Short-Term, and Working Memory
|
– Working memory: Temporary information storage
Look at figure on page 729 |
|
|
Types of Memory and Amnesia
|
Amnesia
|
– Amnesia: Serious loss of memory and/or
ability to learn • Causes: Concussion, chronic alcoholism, encephalitis, brain tumor, or stroke |
|
|
Types of Memory and Amnesia
|
Amnesia
|
– Common amnesia: Limited amnesia
|
|
|
Types of Memory and Amnesia
|
Amnesia
|
– Dissociated amnesia: Amnesia, no other cognitive deficit (rare)
|
|
|
Types of Memory and Amnesia
|
Look at figure on page 730
|
|
|
|
Memory consolidation depends on
integrity of hippocampal formation |
Look at slide on lecture 16 slides 6
|
|
|
|
Types of Memory and Amnesia
|
Amnesia
|
– Memory loss related to time
|
|
|
Types of Memory and Amnesia
|
Amnesia
|
– Retrograde amnesia
• Forget things you already knew |
|
|
Types of Memory and Amnesia
|
Amnesia
|
– Anterograde amnesia
• Inability to form new memories |
|
|
Types of Memory and Amnesia
|
Amnesia
|
– Transient global amnesia: Shorter period
• Symptoms: Disoriented, ask same questions repeatedly; Attacks subside in couple of hours; Permanent memory gap |
|
|
The Search for the Engram
|
Hebb and the Cell Assembly
|
– External events are represented by cortical cells
|
|
|
The Search for the Engram
|
Hebb and the Cell Assembly
|
– Cells reciprocally interconnected--> reverberation
|
|
|
The Search for the Engram
|
Hebb and the Cell Assembly
|
– Active neurons—cell assembly
• Consolidation by “growth process” |
|
|
The Search for the Engram
|
Hebb and the Cell Assembly
|
– Active neurons—cell assembly
• “Fire together, wire together” |
|
|
The Search for the Engram
|
Hebb and the Cell Assembly
|
– Hebb and the engram
• Widely distributed among linked cells in the assembly |
|
|
The Search for the Engram
|
Hebb and the Cell Assembly
|
– Hebb and the engram
• Could involve neurons involved in sensation and perception |
|
|
Look at figure on page 734
|
..
|
|
|
|
The Temporal Lobes and Declarative Memory
|
The Effects of Temporal Lobectomy
|
Look at figure on page 739 & 740 &741
|
|
|
The Medial Temporal Lobes and Memory Processing (Cont’d)
|
– DNMS: Delayed non-match to sample - Recognition Memory
Task |
|
|
|
The Medial Temporal Lobes and Memory Processing (Cont’d)
|
– Medial temporal structures: Important for consolidation of
memory |
|
|
|
The Temporal Lobes and Declarative Memory
|
Look at figure on page 742
|
|
|
|
• The Medial Temporal Lobes and Memory Processing (Cont’d)
|
– DNMS: Delayed non-match to sample
|
|
|
|
• The Medial Temporal Lobes and Memory Processing (Cont’d)
|
– Medial temporal structures: Important for consolidation of
memory |
|
|
|
The Temporal Lobes and Declarative Memory
|
• The Medial Temporal Lobes and
Memory Processing |
|
|
|
The Temporal Lobes and Declarative Memory
|
• Memory Functions of the Hippocampus
– Spatial Memory • Morris water maze |
Look at figure on page 746
|
|
|
The Temporal Lobes and Declarative Memory
|
• Memory Functions of the Hippocampus
|
– Spatial Memory and Place Cells
Look at figure on page 748 |
|
|
The Amygdala and Fearful Memories
|
• The Amygdala and Fear
– Amygdala is critical for learned fear |
• fMRI images and PET imaging: Confirm the role of amygdala
|
|
|
The Striatum and Procedural
Memory |
Two elements of basal ganglia--> Striatum
|
– Caudate nucleus
|
|
|
The Striatum and Procedural
Memory |
Two elements of basal ganglia--> Striatum
|
– Putamen
|
|
|
The Striatum and Procedural
Memory |
Rodent Recordings and Lesions in the Striatum
|
– Lesions to striatum: Disrupts procedural memory
|
|
|
The Striatum and Procedural
Memory |
Rodent Recordings and Lesions in the Striatum
|
– Damaged hippocampal system: Degraded
performance on standard maze task |
|
|
The Striatum and Procedural
Memory |
Rodent Recordings and Lesions in the Striatum
|
– Lesion in striatum: Impaired performance of the
light task; Double dissociation |
|
|
The Striatum and Procedural Memory
|
• Habit Learning in Humans and
Nonhuman Primates |
– Striatum in humans plays a role in procedural memory
Look at figure on page 753 |
|
|
The Neocortex and Working Memory
|
The Prefrontal Cortex and Working
Memory |
– Primates have a large frontal lobe
|
|
|
The Neocortex and Working Memory
|
The Prefrontal Cortex and Working
Memory |
– Function of prefrontal cortex: selfawareness,
capacity for planning and problem solving |
|
|
The Neocortex and Working Memory
|
Look at figure on page 755
|
|
|
|
The Neocortex and Working Memory
|
The Prefrontal Cortex
and Working Memory |
– Imaging Working Memory
in the Human Brain • Numerous areas in prefrontal cortex are involved in working memory |
|
|
The Neocortex and Working Memory
|
The Prefrontal Cortex
and Working Memory |
Look at figure on page 757
|
|
|
Concluding Remarks
|
.
|
|
|
|
Learning and memory
|
– Occur throughout the brain
|
|
|
|
Memories
|
– Duration, kind of information stored, and brain structures involved
|
|
|
|
Memories
|
– Distinct types of memory
|
|
|
|
Memories
|
– Different types of amnesia
|
• Multiple brain systems for memory storage
|
|
|
Lecture 17:
Synaptic plasticity Chapter 25 |
..
|
|
|
|
Vertebrate Models of Learning
|
Neural basis of memory:
|
– Learning and memory can result from modifications of
synaptic transmission |
|
|
Vertebrate Models of Learning
|
Neural basis of memory:
|
– Synaptic modifications can be triggered by conversion of
neural activity into intracellular second messengers |
|
|
Vertebrate Models of Learning
|
Neural basis of memory:
|
– Memories can result from alterations in existing synaptic
proteins |
|
|
Vertebrate Models of Learning
|
Synaptic Plasticity in the Hippocampus
– LTP and LTD |
• Key to forming declarative memories in the brain
|
|
|
Vertebrate Models of Learning
|
Synaptic Plasticity in the Hippocampus
– Bliss and Lomo |
• High frequency electrical stimulation of excitatory
pathway |
|
|
Vertebrate Models of Learning
|
Synaptic Plasticity in the Hippocampus
– Anatomy of Hippocampus |
• Brain slice preparation: Study of LTD and LTP
|
|
|
Anatomy of the Hippocampus (rat)
|
Look at figure on page 777
|
|
|
|
Synaptic Plasticity in the Hippocampus
|
Look at figure on page 778
|
|
|
|
Vertebrate Models of Learning
|
• Synaptic Plasticity in
the Hippocampus: – Mechanisms of LTP in CA1 |
• Glutamate receptors mediate
excitatory synaptic transmission – NMDARs and AMPARs |
|
|
Vertebrate Models of Learning
|
Look at figure on page 781
|
|
|
|
Neuronal activity induces LTP and gene expression
|
Look at figure on Lecture 17 slide 4
|
|
|
|
Synaptic Plasticity in the Hippocampus
|
Look at figure on page 781
|
|
|
|
Vertebrate Models of Learning
|
• Synaptic Plasticity in
the Hippocampus (Cont’d) – BCM theory (E.Bienenstock, L.Cooper, P.Munro |
• When the postsynaptic cell is weakly depolarized by other
inputs: Active synapses undergo LTD instead of LTP |
|
|
Vertebrate Models of Learning
|
• Synaptic Plasticity in
the Hippocampus (Cont’d) – BCM theory (E.Bienenstock, L.Cooper, P.Munro |
• Accounts for bidirectional synaptic changes (up or down)
|
|
|
Vertebrate Models of Learning
|
• Synaptic Plasticity in
the Hippocampus (Cont’d) – BCM theory (E.Bienenstock, L.Cooper, P.Munro |
Look at figure on page 782
|
|
|
Synaptic Plasticity in the Hippocampus
|
– LTP, LTD, and Glutamate Receptor Trafficking
|
• Stable synaptic transmission: AMPA receptors are replaced maintaining the same number
|
|
|
Synaptic Plasticity in the Hippocampus
|
– LTP, LTD, and Glutamate Receptor Trafficking
|
• LTD and LTP disrupt equilibrium
|
|
|
Synaptic Plasticity in the Hippocampus
|
– LTP, LTD, and Glutamate Receptor Trafficking
|
• Bidirectional regulation of phosphorylation
|
|
|
LTP, LTD, and Glutamate Receptor Trafficking
|
Look at figure on page 783
|
|
|
|
LTP, LTD, and Glutamate Receptor Trafficking
|
Look at figure on page 784
|
|
|
|
Synaptic Plasticity in the Hippocampus
|
– Evidence linking synaptic plasticity (LTP & LTD)
with memory: • Pharmacological evidence (R. Morris): |
– Both LTP and LTP require the activation of NMDAreceptors
|
|
|
Synaptic Plasticity in the Hippocampus
|
– Evidence linking synaptic plasticity (LTP & LTD)
with memory: • Pharmacological evidence (R. Morris): |
– Injection of NMDA-receptor blockers into the rat
hippocampus results in deficit on water maze task |
|
|
Synaptic Plasticity in the Hippocampus
|
– Evidence linking synaptic plasticity (LTP & LTD)
with memory: • Genetic evidence: |
– deletion of NMDA-receptor restricted to CA1 region in
hippocampus results in: » deficits in LTD & LTP, and |
|
|
Synaptic Plasticity in the Hippocampus
|
– Evidence linking synaptic plasticity (LTP & LTD)
with memory: • Genetic evidence: |
– deletion of NMDA-receptor restricted to CA1 region in
hippocampus results in: » deficit on water maze task |
|
|
The Molecular Basis of Long-Term Memory
|
• Current L&M theory postulates ability of learning
experience to selectively modify individual synaptic weights. |
|
|
|
The Molecular Basis of Long-Term Memory
|
• Short-term memories that last up to an hour involve
covalent modification of existing proteins (transient alterations of synaptic efficacy). |
|
|
|
The Molecular Basis of Long-Term Memory
|
• Long-term memories require new RNA and protein
synthesis (permanent architectural changes). |
|
|
|
The Molecular Basis of Long-Term Memory
|
– Requirement of long-term memory
|
• Synthesis of new protein
|
|
|
The Molecular Basis of Long-Term Memory
|
– Protein Synthesis and Memory Consolidation
• Protein synthesis inhibitors |
– Deficits in learning and memory
|
|
|
The Molecular Basis of Long-Term Memory
|
Look at lecture 17 slide 8
|
|
|
|
Neuronal activity induces LTP and gene expression
|
Look at lecture 17 slide 9
|
|
|
|
Concluding Remarks
|
..
|
|
|
|
• Learning and memory
|
– Occur at synapses
|
|
|
|
• Unique features of Ca2+
|
– Critical for neurotransmitter secretion and muscle
contraction, every form of synaptic plasticity |
|
|
|
• Unique features of Ca2+
|
– Charge-carrying ion plus a potent second messenger
|
• Can couple electrical activity with long-term changes in
brain |
|
|
Synaptic Plasticity in the Cerebellar Cortex
|
– Cerebellum: Important site for motor learning
|
|
|
|
Synaptic Plasticity in the Cerebellar Cortex
|
– Anatomy of the Cerebellar Cortex
• Features of Purkinje cells |
– Dendrites extend only into molecular layer
|
|
|
Synaptic Plasticity in the Cerebellar Cortex
|
– Anatomy of the Cerebellar Cortex
• Features of Purkinje cells |
– Cell axons synapse on deep cerebellar nuclei neurons
|
|
|
Synaptic Plasticity in the Cerebellar Cortex
|
– Anatomy of the Cerebellar Cortex
• Features of Purkinje cells |
– GABA as a neurotransmitter
|
|
|
Synaptic Plasticity in the Cerebellar Cortex
|
Look at lecture 17 slide 10
|
|
|
|
Motor Learning:
|
the climbing fiber carries error signals indicating that a movement has failed to meet expectation,
|
|
|
|
Motor Learning:
|
corrections are made be adjusting the effectiveness of the parallel fiber inputs to the Purkinje cell.
|
|
|
|
Synaptic Plasticity in the Cerebellar Cortex
|
Look at lecture 17 slide 11
|
|
|
|
Synaptic Plasticity in the Cerebellar Cortex
|
Long-Term Depression in the Cerebellar Cortex (Cont’d)
• Cerebellar LTD: |
– Input-specific synaptic modification
|
|
|
Synaptic Plasticity in the Cerebellar Cortex
|
Long-Term Depression in the Cerebellar Cortex (Cont’d)
• Cerebellar LTD: |
– Site of convergence and nature of synaptic changes
|
|
|
Synaptic Plasticity in the Cerebellar Cortex
|
– Mechanisms of cerebellar LTD
• Learning |
– Rise in [Ca2+]i and [Na+]i and the activation of protein kinase C
|
|
|
Synaptic Plasticity in the Cerebellar Cortex
|
– Mechanisms of cerebellar LTD
• Memory |
– Internalized AMPA channels and depressed excitatory postsynaptic currents
|
|
|
Lecture 18:
Neurological and Psychiatric Disorders on ilearn |
..
|
|
|
|
Neurology
|
– Branch of medicine concerned with the diagnosis
and treatment of nervous system disorders |
|
|
|
Neurological disorders
|
– Help illustrate the role of physiological processes
in normal brain function |
|
|
|
Neurological disorders
|
– Examples: spinal cord injuries,
neurodegenerative diseases (PD, AD etc) |
|
|
|
Psychiatry
|
– Branch of medicine concerned with the
diagnosis and treatment of disorders that affect the mind or psyche |
|
|
|
Psychiatry
|
– In Greek mythology, Psyche was personification of human soul
|
|
|
|
Psychiatric disorders
|
– Examples: Anxiety disorders, affective disorders, schizophrenia
|
|
|
|
Mental Illness and the Brain
|
Human behavior
|
– Product of brain activity
|
|
|
Mental Illness and the Brain
|
Brain
|
– Product of two mutually interacting factors: genes and environment
|
|
|
Mental Illness and the Brain
|
Mental illness
|
– Diagnosable disorder of thought, memory,
mood, or behavior that causes distress or impaired functioning |
|
|
Mental Illness and the Brain
|
Mental illness
|
– Earlier belief
• Disorders of the body |
|
|
Mental Illness and the Brain
|
Mental illness
|
– Earlier belief
• Disorders of the mind |
|
|
Mental Illness and the Brain
|
Psychosocial Approaches to Mental
Illness |
– Freud’s theory: Mental illness- Unconscious and conscious elements of psyche come into conflict
|
|
|
Mental Illness and the Brain
|
Psychosocial Approaches to Mental
Illness |
– Skinner: Many behaviors are learned responses to the environment
|
|
|
Mental Illness and the Brain
|
Psychosocial Approaches to Mental
Illness |
– Maladaptive behavior
|
|
|
Mental Illness and the Brain
|
Biological Approaches to Mental Illness
– General paresis of the insane |
• Symptoms: Mania, cognitive deterioration
|
|
|
Mental Illness and the Brain
|
Biological Approaches to Mental Illness
– General paresis of the insane |
• Cause: T. pallidum infection
|
|
|
Mental Illness and the Brain
|
Biological Approaches to Mental Illness
|
– Paul Ehrlich (1910)
|
|
|
Mental Illness and the Brain
|
Biological Approaches to Mental Illness
|
– Penicillin (1928)
|
|
|
Mental Illness and the Brain
|
Biological Approaches to Mental Illness
|
– Mental illnesses traced directly to
biological causes |
|
|
Mental Illness and the Brain
|
Biological Approaches to Mental Illness
|
– Roots of mental disorders
|
|
|
Alzheimer's disease (AD)
|
• neurodegenerative disease
|
|
|
|
Alzheimer's disease (AD)
|
• characterized by progressive cognitive deterioration
|
|
|
|
Alzheimer's disease (AD)
|
• late onset disease
|
|
|
|
Alzheimer's disease (AD)
|
Symptoms:
|
- loss of short-term memory
|
|
|
Alzheimer's disease (AD)
|
Symptoms:
|
- anterograde amnesia and progressing graded
retrograde amnesia |
|
|
Alzheimer's disease (AD)
|
Symptoms:
|
- As the disorder progresses,
- language (aphasia), - recognition (agnosia), - decision-making and planning (loss of functions associated with frontal and temporal lobes of the brain. |
|
|
Alzheimer's disease (AD)
|
• Pathophysiology of AD:
|
– Deposition of the beta amyloid protein.
|
|
|
Alzheimer's disease (AD)
|
• Pathophysiology of AD:
|
– This deposition could result from abnormal
processing (proteolytic cleavage) of the beta Amyloid Precursor Protein (APP). |
|
|
Alzheimer's disease (AD)
|
• Pathophysiology of AD:
|
– AD usually starts in the hippocampal formation
and then spreads along neuronal pathways. |
|
|
Alzheimer's disease (AD)
|
• Genetics of AD:
|
– early onset; inherited dominant cases of AD
with early onset (mean age onset 48-58 years) can be caused by seven different mutations in APP gene (chromosome 21), |
|
|
Alzheimer's disease (AD)
|
• Genetics of AD:
|
– late onset; mutations in Apolipoprotein E4 gene
(Chromosome 19) is the major genetic susceptibility risk factor for late onset AD. |
|
|
Schizophrenia
|
• A Description of Schizophrenia
|
– Severe mental disorder
|
|
|
Schizophrenia
|
• A Description of Schizophrenia
|
– Symptoms of schizophrenia: Loss of contact with reality
|
|
|
Schizophrenia
|
Positive symptoms (abnormal thoughts and
behaviors): |
• Delusions
|
|
|
Schizophrenia
|
Positive symptoms (abnormal thoughts and
behaviors): |
• Hallucinations
|
|
|
Schizophrenia
|
Positive symptoms (abnormal thoughts and
behaviors): |
• Disorganized speech
|
|
|
Schizophrenia
|
Positive symptoms (abnormal thoughts and
behaviors): |
• Grossly disorganized behavior
|
|
|
Schizophrenia
|
Negative symptoms (absence of responses):
|
• Reduced expression of emotion
|
|
|
Schizophrenia
|
Negative symptoms (absence of responses):
|
• Memory impairment
|
|
|
Schizophrenia
|
Negative symptoms (absence of responses):
|
• Difficulties in initiating goal-orienting behavior
|
|
|
Schizophrenia
|
Negative symptoms (absence of responses):
|
• Poverty of speech
|
|
|
Schizophrenia
|
• Biological Bases of Schizophrenia
|
– Genes and the Environment
• Schizophrenia: A genetic disorder |
|
|
Schizophrenia
|
• Biological Bases of Schizophrenia
|
– Patients performed a working memory
task but there is decrease in prefrontal cortex activity |
|
|
Schizophrenia
|
• Biological Bases of Schizophrenia
|
– The Dopamine Hypothesis: Psychotic episodes in
schizophrenia triggered by activation of dopamine receptors |
|
|
Schizophrenia
|
Biological Bases of Schizophrenia
|
– The Glutamate Hypothesis
• Behavioral effects of phencyclidine (PCP) – Introduced in1950s as an anesthetic – Inhibits NMDA receptors |
|
|
Schizophrenia
|
Biological Bases of Schizophrenia
|
– Glutamate: Fast excitatory
neurotransmitter in the brain, two important receptor subtypes, AMPA and NMDA |
|
|
Schizophrenia
|
Treatments for Schizophrenia
|
– Consists of drug therapy combined with psychosocial
support |
|
|
Schizophrenia
|
Treatments for Schizophrenia
|
– Conventional neuroleptics, such as chlorpromazine
and haloperidol, act at D2 receptors • Reduce the positive symptoms of schizophrenia • Also have numerous side effects |
|
|
Schizophrenia
|
Treatments for Schizophrenia
|
– Neuroleptic drugs (clozapine)
|
|
|
Schizophrenia
|
Treatments for Schizophrenia
|
– Atypical neuroleptics (No effect on D2): Clozapine
|
|
|
Schizophrenia
|
Treatments for Schizophrenia
|
– NMDA receptor
– Future directions: increased responsiveness of NMDA receptors and with decreasing D2 activation) |
|
|
Parkinson’s Disease (PD)
|
• PD is a degenerative disorder
|
|
|
|
Parkinson’s Disease (PD)
|
• impairs the sufferer's motor skills and speech
|
|
|
|
Parkinson’s Disease (PD)
|
• it is principally a disease of the elderly
|
Look at lecture 18 slide 10
|
|
|
Parkinson’s Disease (PD)
|
• S. Nigra
|
|
|
|
Parkinson’s Disease (PD)
|
The Motor Loop
|
Look at lecture 18 slide 10
|
|
|
Parkinson’s Disease (PD)
|
L-dopa
|
Look at lecture 18 slide 11
|
|
|
Huntington disease (HD)
|
• neurodegenerative disease
|
|
|
|
Huntington disease (HD)
|
• rare inherited neurological disorder affecting up to
8 people per 100,000 |
|
|
|
Huntington disease (HD)
|
• HD is caused by a trinucleotide repeat expansion
in the Huntingtin (Htt) gene |
|
|
|
Huntington disease (HD)
|
• one of several polyglutamine (or PolyQ) diseases
|
|
|
|
Huntington disease (HD)
|
• mHtt causes cell (neuron) death in selective areas
(basal ganglia) of the brain. |
|
|
|
Amyotrophic Lateral Sclerosis (ALS)
|
• ALS, (Lou Gehrig’s disease) is
|
– a progressive, fatal neurodegenerative disease
|
|
|
Amyotrophic Lateral Sclerosis (ALS)
|
• ALS, (Lou Gehrig’s disease) is
|
– eurodegeneration of lower motor neurons and
upper motor neurons that control voluntary muscle movement. |
|
|
Amyotrophic Lateral Sclerosis (ALS)
|
• ALS, (Lou Gehrig’s disease) is
|
– muscle weakness and atrophy throughout the
body. |
|
|
Myasthenia Gravis (MG)
|
• neuromuscular disease
|
|
|
|
Myasthenia Gravis (MG)
|
• characterized by weakness and fatiguability of
voluntary muscles. |
|
|
|
Myasthenia Gravis (MG)
|
• Autoimmune desease
. |
|
|
|
Myasthenia Gravis (MG)
|
• circulating antibodies that block acetylcholine
receptors at the post-synaptic neuromuscular junction, inhibiting the stimulative effect of the neurotransmitter acetylcholine |
|
|
|
Myasthenia Gravis (MG
|
• Myasthenia is treated with immunosuppression
and/or cholinesterase inhibitors. |
Look at lecture 18 slide 13
|
|
|
Concluding Remarks
|
..
|
|
|
|
• Impact of neuroscience on psychiatry
|
.
|
|
|
|
• Mental illness associated with
neurodegenerative disorders |
.
|
|
|
|
• Chemical synaptic transmission is affected by drugs
|
.
|
|
|
|
• Genes and environment play an
important role in diseases such as schizophrenia |
.
|
|
