lecture 7 LOs Flashcards
what projection neurons use glutamate
all pyramidal cells in cerebral cortex
projection neurons of hippocampus, amygdala, thalamus
glutamate projection neurons embedded in other subcortical neclei
what is glutamate ionized by
the amino acid glutamic acid
what does glutamate serve as and what is it a component of
serves as a neurotransmitter
component of many proteins and has other metabolic roles
what is glutamate synthesized by
glutamine by glutaminase
what vesicular transport moves glutamate into synaptic vesicles
VGLUT
where are VGLUT transporters found
in glutaminergic neurons
what is VGLUT the primary marker for
neurons that use glutamate as a neurotransmitter
what else can VGLUT be expressed with
markers of other transmitters, implying that glutamate can be stored and released as a co transmitter (as well as a primary transmitter)
what happens after glutamate release
it is rapidly removed from the synapse by excitatory amino acid transporters (EAAT1 to EAAT5)
where is EAAT1 found
on astrocyte glia (90% of glutamate reuptake)
where is EAAT3 found
on post synaptic membranes
what are astrocyte transporters involved in
glia-neuron metabolic partnership
majority of glutamate reuptake is done by ____ and then what does it do
astrocytes
then convert glutamate to glutamine by glutamine synthesis
where is glutamine transported after glutamine synthesis
out of astrocyte and back to neuron
three subtypes of ionotropic gluatmate receptors
AMPA - named for selective agonist
Kainate - named for selective agonist Kainic acid
NMDA - named for an agonist
how many sub unit proteins do ionotropic receptors consist of
four, but each of the three receptor subtypes have different combos to explain the differences in their pharmacology
what does activation of AMPA/kainate receptors allow the entry of
Na+, depolarizes the neuron
how are AMPA/kainate activated
always activated when there are sufficient stimulation by glutamate
what happens to AMPA/Kainate when too much stimulation occurs
receptor desensitization
what does NBQX do to receptors
a competitive antagonist that blocks both AMPA and Kainate receptors
what is the result of NBQX
sedation, reduced locomotor activity, ataxia, potection against seizures
what does NMDA allow into the neuron
both Na+ and Ca2+
causes greater depolarization than AMPA/Kainate
what is required to open the NMDA channel
both glutamate and glycerine or D-serine must bind at the same time (co-agonists)
when the NMDA neuron is at rest, what is blocking the channel
Mg2+
what does repeated AMPA receptor activation do
can depolarize the neuron enough to remove Mg2+ blockage and allow NMDA receptor to activate
what does AP-5 do
competitve antagonist that blocks glutamate binding
what blocks the NMDA channel when it is open
phencyclidine (PCP), ketamine, and MK-801
what can phencyclidine (PCP), ketamine, and MK-801 cause for symptoms
schizophrenia like symptoms at lower doses
ataxia (inability to move) and anesthesia at higher dose
what do drugs that target the glycine binding site do
act as a non competitve antagonist
does NMDA or AMPA/Kainate cause larger/longer lasting depolarization
NMDA
what does NMDA receptor activity do to the neuron
depolarize it
alter firing patterns (promote burst firing)
metabotropic glutamate receptors
mGluR1 to mGluR8
act through G-proteins and second messenger systems
which of the mGluR are postsynaptic and which are presynaptic
mGluR1 and 5 are postsynaptic
mGluR2-4 and 6-8 are presyanptic
what do presynaptic mGlurRs act as
autoreceptors or heteroreceptors
suppress glutamate release (or release of other transmitters)
what is L-AP4
agonist at mGluR 4,6,7,8 autoreceptors
what does L-AP4 do
treatment with this frug reduces glutamate signalling by depressing release
what do mGluRs participate in
functions such as locomotion, motor coordination, cognition, mood and pain perception
how are alterations in the activity of synapses measured
synaptic strength
how is synaptic strength measured and what does it mean
typically measured by changes in post synaptic potential evoked by an input
increased strength = larger EPSP evoked in postsynaptic neuron
primarily measured with electrophysiological methods
steps of long term potentiation
1: stimulate presynaptic axons at low frequency to get subthreshold EPSP (no AP), establish baseline
2: stimulate axons at very high frequency and get lots of AP in post synaptic neuron
3: axons at low frequency again, same subthreshold current = much bigger EPSP than before
early phase LTP
high frequ activation of postsynaptic neuron allows NMDA receptor to be activated (Ca2+ entry into neuron)
ca2+ activates enzymes (kinases) including calcium-calmodulin (CaM)
CaM kinase hits AMPA receptor floating in the cell and insterts in the membrane (resulting in more receptors)
other kinases (protein kinase C) can induce formation of retrograde messenger (molec that goes from postsynaptic neuron to presynaptic terminal, promotes transmitter release)
dendritic spines undergo structural change to be more excitable
increased synaptic strength by both pre and post synaptic mechanisms
what happens in late phase LTP
cell synthesizes new proteins that make the changes longer lasting
what does a blockade of NMDA receptors impair
many forms of learning mediated by different systems (hippocampus, amygdala, striatum)
when glutamate activity is slightly enhanced what happens
can improve learning/memory
what does ampakine do
positive allosteric modulator of AMPA receptor, increases cognition in normal animals and in animal models w cognitive dysfunction
