Glutamate Receptors and Systems Flashcards
of the metabotropic receptors, group 2 and 3 are inhibitory, excitatory or modulating?
inhibitory
group 1 metabotropic receptors are inhibitory, excitatory or modulating?
modulating
where are group 2 and 3 metabotropic receptors found
pre synaptically
where are group 1 metabotropic receptors found
post synaptically
mGluR1 KO shows ______
motor dysfunction
mGluR2 KO shows ____
normal synaptic transmission
mGluR4 KO shows _____
loss of synaptic efficiency during repetition
where is the mGluR2 KO expressed
dentate gyrus
what is CaMK2
calmodulin dependent kinase 2
____ is tightly coupled to Ca dependent proteins
NMDAR
what is the difference between LTD and LTP
LTP -> persistent increase in synaptic activity
LTD -> persistent decrease in synaptic strength after slow repetition
the hippocampus is involved in what
learning and memory
what is the pathway of the hippocampal slice preparations
PP -> DG -> CA3 -> CA1
how is hippocampal slices prepared
ex vivo
see slide 7 for diagram
what is the function of CaMK2
phosphorylates cellular targets and initiates early LTP
what activates CamK2
calcium entry through NMDAR
what do retrograde messengers in LTP process do
signal the presynaptic cell -> initiates presynaptic changes -> increase glutamate
what does CamK2 phosphrylate
AMPAR
activation of CamK2 and ___ converge on another kinase, ERK
PLC
what is ERK
triggers downstream changes -> phosphorylation and TFs
gene synthesis increases ____ receptors
AMPA
LTP inductions depends on ___
NDMAR
what does overexpression of NMDAR lead to in mice
increases learning
what is important about Doogie mouse
overexpresses NMDAR -> increased retention in novel recognition tasks
excitotoxicity leads to what problems
ischemia, ALS, alcoholism and MS
what is Lytigo-bodig disease
neurodegenerative disease that has similar symptoms to ALS and PD
what does BMAA stand for
beta-methyl-amino-L-alanine
what does Lytigo bodig disease come from
cycad seeds
true or false - the cycad seeds affect the bats
false - they only affect humans when they eat them
what does a mutation in ALS lead to
increased intracellular calcium in motor neurons -> stresses out mitochondria
EATT2 dysfunction leads to what
glutamate accumulation and excitotoxicity
describe the mechanisms of what happens in ischemia
loss of blood flow to CNS -> lack of oxygen and glucose -> lack of ionic gradients -> dump glutamate -> increased intracellular calcium -> failed EAAT transport
______ is uncontrolled cell death
necrosis
______ is programmed cell death
apoptosis
what is an analogy for necrosis
a water balloon that has been filled too much and it ruptures and explodes
in apoptosis , what is damaged
the mitochondria from swelling -> pores form -> cell death
what gradient is involved in apoptosis
calcium influc
what helps remove cell material in apoptosis
phagocytic cells
in animal models, NMDA and AMPA antagonists can do what
reduce the volume of injury in ischemic stroke
true or false - NMDA and AMPA antagonists can be injected into humans for reduction of brain injury
false
look at slide 18 diagram
what % of epilepsy is convulsive
60%
what is the most common seizure type in children
febrile seizures
epileptic seizures are dependent on ____
glutamatergic signalling
_______, _____, ______ are convulsants
kainate, AMPA, domoic acid
agonists or antagonists of AMPAR can prevent seizure onset , what is an example
antagonists -> NBQX
agonists or antagonists of NMDAR can reduce intenisty and duration of seizures , what is an example
antagonists , MK801
what are examples of glutamate receptors
AMPA, kainate and NMDA
what is involved in glutamate recycling
glutamine synthetase and glutamate dehydrogenase
what is a drug class that is not tested against placebo
anticonvulsants and antiepileptic drugs
___ % of patients are unresponsive to AED therapy
30
what do AEDs target
Na channel activity or increase inhibitory signalling by affecting GABA
other than AEDs what is another common technique used to treat epilepsy and what does this do for seizures
corpus callostomy -> decreases frequency and amplitude of seizures by disrupting bilateral synchronous signals
what is a side effect of corpus callostomy
speech irregularities
