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Alexey Semyanov "Extrasynaptic signaling mediated by GABAA and NMDA receptors in the hippocampus"

Abstract :


Synaptic signaling and plasticity are thought to be the main mechanisms for information processing and storage in the brain.
The communication between brain cells (neurons and glia), however, is not limited to synaptic signaling. These cells express various types of high affinity extrasynaptic receptors which are able to detect ambient neurotransmitters.
We investigated the functions of extrasynaptic GABAA and NMDA receptors. We found that ambient GABA, the main inhibitory neurotransmitter in the brain, can excite adult hippocampal interneurons. In these cells GABA is depolarizing which makes baseline tonic GABAA conductance excitatory. Increasing the tonic conductance enhances shunting-mediated inhibition, which eventually overpowers the excitation.
In contrast to GABAA receptors extrasynaptic NMDA receptors do not mediate tonic current at baseline conditions because of voltage-dependent channel block by Mg2+. We found that in CA1 pyramidal neurons backpropagating action potentials (bAPs) unblock dendritic-shaft NMDA receptors exposed to ambient glutamate. By modulating NMDA receptor-mediated dendritic Ca2+ entry, this activation thus informs the cell about the extracellular glutamate concentration in the local neuropil. The recruitment of extrasynaptic NMDARs by bursts of bAPs leads to increased Ca2+ entry though these receptors. Consequently, activation of extrasynaptic NMDARs by theta-bursts of bAP causes Ca2+ dependent neuronal plasticity (downregulation of h-channel mediated membrane conductance). 

Selected publications

Tonic excitation or inhibition is set by GABA(A) conductance in hippocampal interneurons.Song I, Savtchenko L, Semyanov A.Nat Commun. 2011 Jul 5;2:376. doi: 10.1038/ncomms1377.
Network with shunting synapses as a non-linear frequency modulator.Kochubey S, Semyanov A, Savtchenko L.Neural Netw. 2011 Jun;24(5):407-16. Epub 2011 Mar 11.

Valentin Nagerl de l'IINS