GLUTAMATERGIC EXCITATORY NEUROTRANSMISSION AND SYNAPTIC PLASTICITY Flashcards
There are distinct gene families that underpin the 3 main subtypes of inotropic glutamate receptor what are they?
AMPA
kainate
NMDA receptors
AMPA and NMDA receptors act in a coordinate dmanner to mediate what
Neuronal excitation
Inotropic glutamate receptors mediate a form of what?
Synaptic plasticity called long term potentiation (LTP)
This is consodered as a possible synaptic correlate of learning and memory
Magnesium does what to the NMDA receptor associated ion channel
Describe what it does
Mg is a a voltage and use dependant blocker
NMDAR conducts NA+, Ca2+ and K+ but is blocked by Mg2+
Ketamine is also a blocker of this channel
What does the NMDAR channel require for it to open
Needs to be activated by glutamate or NDMA by the co-agonist glycine
What is the NDMA
It is a family of L-glutamate receptors, play an important role in learning and memory, and are critical for spatial memory. These receptors are tetrameric ion channels composed of a family of related subunits.
What patch clamp technique is used to look at the Mg2+ effects on NDMA
OUTSIDE-OUT
At what mV is Mg able to block the channel?
-60mV
What does the activation of NDMA receptors require
the binding of glutamate and the binding of the co-agonist glycine (or D-serine)
In the absence of glycine, glutamate does induce a current-due to activation of AMPARs-but in the presence of glycine what happens
That current is greatly increased as now glutamate additionally activates NMDARs
Explain the process of the synergisitc interplay of synaptic AMPA receptors and NMDA receptors at an excitary synapse
- Neurally released glutamate activates synaptic AMPA receptors, but although glutamate also binds to NMDA receptors the associated ion channel does not initially conduct due to ion channel blockade by Mg2+
- The Na influx caused by activation of AMPA receptors causes a depolarisation of the neuronal spine. if the presynaptic glutamergic nerve fires at high frequencies, or multiple glutamergic inputs are stimulated then the depolarisation may be sufficient to cause Mg2+ unblocking of the NMDA receptor and consequently the appearance of a slow prolonged synaptic depolarisation, mediated by NMDARs
High frequencies of presynaptic activity and stimulation of multiple glutamergic input neurons facilitates what
NMDA receptor activation
At high frequencies of presynaptic stimulation the depolarisation of the postsynaptic neuron by glutamate activation of AMPARs is sufficient to relieve what
The magnesium block of the NMDAR
What are required as a co-agonist to activate the NMDAR-associated cation channel
Glycine or D-serine
For the NMDA receptor what conducts inwardly and outwardly
Na+/Ca2+ - inwardly
K+ - outwardly
At negative membrane potentials- Its blocked by magnesium
All ionotrpic glutamate receptors are what shape
Tetrameric assemblies of 4 subunits
What are AMPARs
heterotetrameric complexes composed of subunits GluA1–4
Ca2+ permeable
Blocked by endogenous polyamines
Why is the GluA2 subunit critical for the AMPAR
Determines receptor function. Incooperation of the GluA2 subunit imparis Ca2+ permeability and prevents polyamine block
The permeability to Ca2+ is dictated by what
the nature of a single amino acid located in the ion conducting pore
In the adult how much % is GluA2 edited
95%
Spermine acts as what in AMPAR
Acts as an intracellular AMPAR ion channel antagonist to block the outward current carried by cations
Describe the structure of thr NMDA receptor
- Most are composed of GluN1 and GluN2 subunits
- The NMDAR subunits have a similar topology to the AMPA and kainate subunits
- The GluN1 subunit binds Glycine/D-Serine and the GluN2 subunit binds Glutamate
What are Quantum dots
tiny (nanometer) semiconductor particles
How can the movement of receptors and live neurons be monitored
Using fluorescent quantum dots and high resolution microscopy
