Week 5 Flashcards
What are the two major classes of GABA receptors?
GABA.A and GABA.B
How is GABA formed
Glutamate reacted with GAD
How do these two classes of GABA receptors inhibit neuronal activity?
GABA.A:
- Ligand-gated ionotropic
- Leads to Cl- inflow.
- Fast inhibition
- 10-20ms conductance (vs 2ms for AMPA)
- -ve reversal potential (=> positive current at 0mV)
GABA.B:
- G-protein-coupled metabotropic receptor
- Slower form of inhibition
- activates GIRK channels (K+ outflow) to slow AP.
- Can also inhibit Ca2+ inflow at presynaptic bouton.
What is the significance of glycine
The GABA equivalent of the spinal cord
What is the significance of gephryn
keeps the GABA receptors in place
What is meant by ‘shunting’ inhibition
V.m ~= E.Cl. So why does GABA opening impact EPSP?
Larger overall membrane conductance for EPSP => smaller time constant => smaller and quicker EPSP.
Describe the mechanism of action of benzodiazepines.
- Sits in between the alpha and gamma subunits of the GABA.A receptor; GABA binding site is between the alpha and beta.
- Increases likelihood of GABA binding with GABA.A receptor
- GABA.A will need to have alpha1,2,3or5 (not 4,6) in order to be affected by benzodiazepines
Describe a ‘feedback inhibition’ circuit of the thalamus.
- For a strong stimulus to sensory nerves, an AP is sent up to reticular nucleus
- Immediately an inhibitory GABA signal is sent back to blunt any close-to-AP V.m in the sensory cells of that region
- End result is that only very strong stimuli are noted by the brain when they exist
What types of GABAergic neurons are present in the neocortex and what functions might they serve?
1) Parvalbumin-expressing cells (fast-spiking, most common):
form synapses with AIS (chandelier cells, control EXC output) or innervate soma/proximal dendrites (basket cells, fast GABA.A inhibition). Form excitatory/inhibitory microcircuits.
2) Somatostatin-expressing:
innervate with distal dendrites of excitatory neurons. Receive facilitative excitatory input from nearby pyramidal neurons. They are the dendritic gating in layer 1
3) VIP-expressing
Inhibit (1) and (2), so net LESS inhibition. Receive nicotinic excitation
4) Neurogliaform / Neuronal No Synthase
Dense axonal arborisation. No clear receiving neuron means they probably project, regulate GABA levels locally, => slow GABA.B inhibition
Why is the concentration of CL- so low in neurons in the first place? Why is this different at early age?
V.m < 0 so Cl- leaks out
KCC2 is not well expressed => reversal potential of Cl- is more positive than in adults (-40mV not -80mV) => Cl- flows OUTWARD
How long is the open conductance of GABA.A? How does this compare to AMPA?
20ms, about 10x longer than AMPA
What is the role of dopamine
Acts on D1 and D2 receptors in the striatum
Important for reward driven decision making
What is the role of Purkinje cells
GABAergic projection neurons which inhibit deep cerebellar nuclei.
What is an excitatory and inhibitory microcircuit?
Excitatory neurons both propagate signals to where is needed to go AND to inhibitory neurons, which in turn dampen that excitatory neuron to prevent overly rapid firing.
