PSYC20006 Lecture Notes - Lecture 23: Nmda Receptor Antagonist, Excitatory Synapse, Ketamine
12 Jun 2018
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Lecture 22 - Thursday 25 May 2017
PSYC20006 - BIOLOGICAL PSYCHOLOGY
LECTURE 23
PART 1: GLUTAMATE & GABA
TODAY
•Glutamate & GABA Overview
•Glutamate & GABA Synthesis/Release
•Glutamate & Drugs
•GABA and Inhibition
•GABA & Seizure disorder
•Course summary
GLUTAMATE & GABA
•Glutamate & GABA both believed to be the first to evolve and are found in very simple organisms
•Glutamate & GABA are the most common neurotransmitters in the CNS
•Glutamate & GABA both act as a “true” neurotransmitter – directly affecting the likelihood of
the post-synaptic neuron firing
GLUTAMATE
•Glutamate is the MAIN excitatory neurotransmitter in the brain (increasing likelihood of the
post-synaptic neuron firing)
•The neurotransmitter released by
ALL excitatory neurons.
•Estimated that over half of all
brain synapses release Glutamate
GLUTAMATE SYNTHESIS
•Glutamate = Glutamic Acid
•Glutamate is an amino acid that
acts as a neurotransmitter in its
“original” form but this amino
acid does not pass the blood brain
barrier so it still needs to be
synthesized in the brain
•Is synthesized from glutamine
which is released by cells
neighboring the neurons
EXCITATORY NTs
•Found in most of the long
projection neurons throughout the
cortex (pictures right, below)
•Excitatory connections are
“point-to-point”.
•Many region-specific functions (e.g.
Connections along the visual pathways)
•Information flow through the “Visual
Hierarchy”
Lecture 22 - Thursday 25 May 2017
PSYC20006 - BIOLOGICAL PSYCHOLOGY
NMDA RECEPTORS
•There are multiple types of Glutamate
receptors.
•One is the NMDA receptor which is
particularly complex! It has at least 6
different binding sites so has lots of
complex functions (has 6 different things
that can bind to it that will then change the
conformation)
•For example it only works if:
•1) there is also a glycine molecule
(another amino acid) attached.
•2) if magnesium ion is NOT bound to
inside.
•The other binding cites modulate receptor
function.
•Implicated in disorders and brain function
in general.
ALCOHOL
•Alcohol is an NMDA antagonist
•Reduction in glutamate is believed to contribute both to the general sedative effects & memory
effects of alcohol
•Alcohol is also GABA agonist which further leads to brain inhibition.
PCP & KETAMINE
•Phencyclidine (PCP) = “Angel dust”
•Ketamine =“Special K”, Horse tranquilizer
•Both are NMDA antagonists
•Both cause dissociative hallucinations (people feel disconnected rather than perceiving visions etc)
•Risk of suicidal behavior (ketamine itself is remarkably safe on the body)
•Most hallucinogens are serotonergic.
NMDA RECEPTORS CONTINUED
•Alcohol, PCP and Ketamine all act principally as NMDA antagonists but have different effects on
the mind
•The exact mechanisms of action are not completely known but because all 3 drugs effect some
additional receptors it illustrates how complex drug/brain effects can be.
•NMDA Receptors provide a great illustration of the complexities of psychopharmacology
GLUTAMATE & PSYCHOSIS
•Links between glutamate & dopamine and psychosis.
•Psychosis = Symptom Cluster not a Diagnosis
•Schizophrenia ~1% population > psychosis ~ 3%
•Delusions
•Hallucinations
•Depression
•Anxiety
•Suicidal thoughts or actions
•Difficulty functioning
•Disorganized speech—switching topics erratically
•Some have suggested a link between Glutamate & Psychosis, but this is controversial and is likely
to involve other neurotransmitters such as DA.
Document Summary
Today: glutamate & gaba overview, glutamate & gaba synthesis/release, glutamate & drugs, gaba and inhibition, gaba & seizure disorder, course summary. Glutamate: glutamate is the main excitatory neurotransmitter in the brain (increasing likelihood of the post-synaptic neuron firing, the neurotransmitter released by. All excitatory neurons: estimated that over half of all brain synapses release glutamate. Glutamate synthesis: glutamate = glutamic acid, glutamate is an amino acid that acts as a neurotransmitter in its. Original form but this amino acid does not pass the blood brain barrier so it still needs to be synthesized in the brain: is synthesized from glutamine which is released by cells neighboring the neurons. Excitatory nts: found in most of the long projection neurons throughout the cortex (pictures right, below, excitatory connections are. Point-to-point : many region-specific functions (e. g. connections along the visual pathways, information flow through the visual.
