BIOC14H3 Lecture Notes - Lecture 2: Gaba Receptor Agonist, Dopamine Antagonist, Human Genome Project

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5 Feb 2013
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BIOC14Winter2013 Lecture 2 Notes
CHAPTER 3: NEUROGENETICS AND NEUROPHARMACOLOGY
Genes shape behavior at multiple levels
o
o the environment can affect each step
o the way you are raised can also affect gene expression and the way we behave
Neuron
o
o the axon is myelinated to increase signal transduction
Synaptic Transmission
o
o both in CNS and PNS
o signal starts at the soma (the cell body of the neuron)
o the resting membrane potential is of -70mV
o voltage gated Na channels open, allowing Na to come
in so the inside of the neuron depolarized (becomes
more positive)
o this starts a chain reaction so depolarization
continus along the membrane (propagates down the
neuron as the positive charge reaches and causes
other voltage gated channels to open)
o eventually they reach the Ca channels and Ca comes
in
o Calcium influc causes the vesicles to move to the
membrane and fuse, releasing neurotransmitters
into the synaptic cleft
o The neurotransmitters bind to receptors on the post
synaptic neuron
Gene shapes behavior at multiple levels
DNA
(gene)
RNA
Cells
(Neurons)
Protein
Brain
(Group of neurons and their interconnections)
Behaviors
(actions, responses, emotion, personality, etc)
genome
transcriptome
connectome
proteome
Behavioral repertoire
Environments
(physical, chemical, biological, social, economical, etc.)
3
- the environment can affect each
step
- the way you are raised can also
affect gene expression and the way
you behave
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2
o After a period of time they can diffuse away or they can be reuptaken by the presynaptic neuron
Synaptic Transmission
o Amino acids:
o Acetylcholine stimulatory at the neuromusculatory junction and inhibitory in the heart
o Gamma aminobutyric acid (GABA) inhibits 90% of all synapses
o Glycine, Glutamate (activator), Aspartate
o Biogenic amines organic compounds with multiple amine groups
o Dopamine, Noradrenaline, Serotonin, Histamine
Synaptic Reception
o Neurotransmitter receptors in postsynaptic neuron memebrane bind NTs that are released from pre-synaptic neurons
o NT receptors influence the opening and closing of ion channels
o NT receptors can be divided into 2 classes depending on how they influence the ion channels
Ionotropic Receptors
o Ionotropic receptors function both as receptors and ion channels
o Upon binding of NT, the receptor undergoes conformation change that results in the opening of the channel ions of
appropriate size and charge can come in the cell
o The cell memebrane potential then changes when Na comes in membrane potential increases, while when Cl ions come in
the memebrane potential further decreases (more difficult for an action potential to be created)
o
Metabotropic Receptors
o metabotropic receptors influence ion channels indirectly
o upon binding, metabotropic receptors activate cascade of signaling events involving G protein signaling and second
messeneges (cAM and DAG)
o activation of second messengers in turn activate protein kinases that phosphorylate different substrate proteins including
ion channels
o also affect cell function over longer term by changing the synthesis of new proteins
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o
o the receptor is bound to G protein
o conformation change in G protein occurs activates adenylyl cyclase cAMP protein kinase A is activated which
phosphorylates channels and causes opening or closing of ion channels
Synaptic Integration
o multiple synaptic potentials can piggy back on each other
o excitatory and inhibitory synaptic signals are integrated into a single response
o one signal from a neuron to another is no enough to fire and AP because there mey be contradictory messeges
o temporal summation when more than one neuron transmit the same signal one after the other so the neuron has no time
to recover, adding up the signal and causing the firing of an action potential
o
o Spatial summation all signals come at once, some may be inhibitory and some may be excitatory, but added up they may
or may not result in an action potential
Influence of Genes on Neuronal Functions and Behaviors
o
o Depression: serotonin is taken out of the cleft and is repackaged so that amount of serotonin in the cleft differs than a
“normal” person
o Schizophrenia: overstimulation of dopaminergin neurons = too much dopamine
o A deficit of dopamine can also cause ADHD
o * Neuropharmacology the branch of research concerned with drugs affecting the nervous system
SSRI
o selective serotonin reuptake inhibitor
o a class of drugs used as antidepressents fluoxetine (Prozac), sertraline (Zoloft), citalopram (Celexa)
Synaptic integration
Multiple synaptic potentials can piggy back on each other.
Excitatory and inhibitory synaptic signals are integrated into a single response.
Temporal summation
Spatial summation
12
- one signal from a neuron to another is not
enough to re an AP because there may be
contradictory messeges
- temporal summation --> when more than
one neuron transmit the same signal at the
one after the other so the neuron has no time
to recover, adding up the signal and causing
the ring of an action potential
- all signals come in at once, some may
be inhibitory and some may be
excitatory
Synaptic integration
Multiple synaptic potentials can piggy back on each other.
Excitatory and inhibitory synaptic signals are integrated into a single response.
Temporal summation
Spatial summation
12
- one signal from a neuron to another is not
enough to re an AP because there may be
contradictory messeges
- temporal summation --> when more than
one neuron transmit the same signal at the
one after the other so the neuron has no time
to recover, adding up the signal and causing
the ring of an action potential
- all signals come in at once, some may
be inhibitory and some may be
excitatory
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