Glutamate Flashcards
Glutamate
- Found everywhere in brain
- Not localized (synthesized everywhere)
- Excitatory amino acid neurotransmitter
- Binds to receptor, opens NA channels, causes depolarization
Glutamate Synthesis Cycle:
• Astrocyte removes glutamate from synapse and breaks it down
• Glutamine is converted to glutamate via glutaminase
• Glutaate packaged into vesicles containing VGLUT
o Vesicular Glutamate Transporter
• VGLUT load vesicles with neurotransmitter
• Too much glutamate kills neurons (occurs in stroke)
• EAAT (Excitatory amino acid transporter) removes any excitatory amino acid (not just glutamate)
Glutamate Receptors:
NMDA
AMPA
Metabotropic glutamate receptor
Kainate receptor
NMDA Receptor
o Important for formation of memories
o Transports Ca when activated (Ca can act as second messenger)
o Acts as both ionotropic and metabotropic receptors
o Conducts both Na and Ca
o Made of 4 subunits with various binding sites
o Opens when pre and post synaptic neurons are firing together (coincidence detector- helps wire cells together)
AMPA Receptor
Inotropic
Metabotropic Glutamate Receptor
o Sends second messengers, can cause negative feedback
Kainite Receptor
o Ionotropic
NMDA Binding Sites
Glutamate
Glycine
PCP
Magnesium
PCP Binding Site
o Binding site is within channel
o Inhibitory effects
o Blocks channel, but doesn’t compete with glutamate
Magnesium Binding Site
o Blocks channel, when bound, Ca and Na can’t go through
o Mg binds at -70 mV removed at -65 mV
NMDA Receptor Subtypes:
- NR1, NR2A, NR2B
- All NMDA have 2 NR1 subtypes, but can vary by whether they have NR2A or NR2B subtypes
- NR2B receptors are more sensitive, causes more Ca to enter cell
Long Term Potentiation
- Can be produced by experiences that result in learning
* NMDA dependent
CA1 Knockout
- Disrupted circuit to disrupt hippocampus dependent memory storage
- Determined that NR1 subunit in CA1 is needed to produce LTP (electrode stimulation) and for Place Learning (water maze test)
NR2B Overexpression:
- Enhanced LTP, spatial learning
* Acquired memory more quickly, are better learners