lecture 7 LOs

Question 1

what projection neurons use glutamate

Answer 1

all pyramidal cells in cerebral cortex
projection neurons of hippocampus, amygdala, thalamus
glutamate projection neurons embedded in other subcortical neclei

Question 2

what is glutamate ionized by

Answer 2

the amino acid glutamic acid

Question 3

what does glutamate serve as and what is it a component of

Answer 3

serves as a neurotransmitter
component of many proteins and has other metabolic roles

Question 4

what is glutamate synthesized by

Answer 4

glutamine by glutaminase

Question 5

what vesicular transport moves glutamate into synaptic vesicles

Answer 5

VGLUT

Question 6

where are VGLUT transporters found

Answer 6

in glutaminergic neurons

Question 7

what is VGLUT the primary marker for

Answer 7

neurons that use glutamate as a neurotransmitter

Question 8

what else can VGLUT be expressed with

Answer 8

markers of other transmitters, implying that glutamate can be stored and released as a co transmitter (as well as a primary transmitter)

Question 9

what happens after glutamate release

Answer 9

it is rapidly removed from the synapse by excitatory amino acid transporters (EAAT1 to EAAT5)

Question 10

where is EAAT1 found

Answer 10

on astrocyte glia (90% of glutamate reuptake)

Question 11

where is EAAT3 found

Answer 11

on post synaptic membranes

Question 12

what are astrocyte transporters involved in

Answer 12

glia-neuron metabolic partnership

Question 13

majority of glutamate reuptake is done by ____ and then what does it do

Answer 13

astrocytes
then convert glutamate to glutamine by glutamine synthesis

Question 14

where is glutamine transported after glutamine synthesis

Answer 14

out of astrocyte and back to neuron

Question 15

three subtypes of ionotropic gluatmate receptors

Answer 15

AMPA - named for selective agonist
Kainate - named for selective agonist Kainic acid
NMDA - named for an agonist

Question 16

how many sub unit proteins do ionotropic receptors consist of

Answer 16

four, but each of the three receptor subtypes have different combos to explain the differences in their pharmacology

Question 17

what does activation of AMPA/kainate receptors allow the entry of

Answer 17

Na+, depolarizes the neuron

Question 18

how are AMPA/kainate activated

Answer 18

always activated when there are sufficient stimulation by glutamate

Question 19

what happens to AMPA/Kainate when too much stimulation occurs

Answer 19

receptor desensitization

Question 20

what does NBQX do to receptors

Answer 20

a competitive antagonist that blocks both AMPA and Kainate receptors

Question 21

what is the result of NBQX

Answer 21

sedation, reduced locomotor activity, ataxia, potection against seizures

Question 22

what does NMDA allow into the neuron

Answer 22

both Na+ and Ca2+
causes greater depolarization than AMPA/Kainate

Question 23

what is required to open the NMDA channel

Answer 23

both glutamate and glycerine or D-serine must bind at the same time (co-agonists)

Question 24

when the NMDA neuron is at rest, what is blocking the channel

Answer 24

Mg2+

Question 25

what does repeated AMPA receptor activation do

Answer 25

can depolarize the neuron enough to remove Mg2+ blockage and allow NMDA receptor to activate

Question 26

what does AP-5 do

Answer 26

competitve antagonist that blocks glutamate binding

Question 27

what blocks the NMDA channel when it is open

Answer 27

phencyclidine (PCP), ketamine, and MK-801

Question 28

what can phencyclidine (PCP), ketamine, and MK-801 cause for symptoms

Answer 28

schizophrenia like symptoms at lower doses ataxia (inability to move) and anesthesia at higher dose

Question 29

what do drugs that target the glycine binding site do

Answer 29

act as a non competitve antagonist

Question 30

does NMDA or AMPA/Kainate cause larger/longer lasting depolarization

Answer 30

NMDA

Question 31

what does NMDA receptor activity do to the neuron

Answer 31

depolarize it alter firing patterns (promote burst firing)

Question 32

metabotropic glutamate receptors

Answer 32

mGluR1 to mGluR8 act through G-proteins and second messenger systems

Question 33

which of the mGluR are postsynaptic and which are presynaptic

Answer 33

mGluR1 and 5 are postsynaptic mGluR2-4 and 6-8 are presyanptic

Question 34

what do presynaptic mGlurRs act as

Answer 34

autoreceptors or heteroreceptors suppress glutamate release (or release of other transmitters)

Question 35

what is L-AP4

Answer 35

agonist at mGluR 4,6,7,8 autoreceptors

Question 36

what does L-AP4 do

Answer 36

treatment with this frug reduces glutamate signalling by depressing release

Question 37

what do mGluRs participate in

Answer 37

functions such as locomotion, motor coordination, cognition, mood and pain perception

Question 38

how are alterations in the activity of synapses measured

Answer 38

synaptic strength

Question 39

how is synaptic strength measured and what does it mean

Answer 39

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

Question 40

steps of long term potentiation

Answer 40

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

Question 41

early phase LTP

Answer 41

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

Question 42

what happens in late phase LTP

Answer 42

cell synthesizes new proteins that make the changes longer lasting

Question 43

what does a blockade of NMDA receptors impair

Answer 43

many forms of learning mediated by different systems (hippocampus, amygdala, striatum)

Question 44

when glutamate activity is slightly enhanced what happens

Answer 44

can improve learning/memory

Question 45

what does ampakine do

Answer 45

positive allosteric modulator of AMPA receptor, increases cognition in normal animals and in animal models w cognitive dysfunction