ePoster

Group I metabotropic glutamate receptor-mediated modulation of mono- and disynaptic transmission in the human neocortex

Joanna Sandle, Gábor Molnár, Katalin Kocsis, Martin Tóth, Emőke Bakos, Pál Barzó, Karri Lamsa, Gábor Tamás
FENS Forum 2024(2024)
Messe Wien Exhibition & Congress Center, Vienna, Austria

Conference

FENS Forum 2024

Messe Wien Exhibition & Congress Center, Vienna, Austria

Resources

Authors & Affiliations

Joanna Sandle, Gábor Molnár, Katalin Kocsis, Martin Tóth, Emőke Bakos, Pál Barzó, Karri Lamsa, Gábor Tamás

Abstract

Activation of group I metabotropic glutamate receptors (mGluR) in the brain mediates changes in neuronal excitability, synaptic transmission, and network activity of cortical circuits and has been linked to learning-related plasticity, brain state-modulation as well as various human neurological disorders but studies investigating their effect in human brain are scarce and mostly focused on excitatory neurons. We studied the effects of group I mGluR activation on monosynaptic glutamatergic synapses arriving onto interneurons and disynaptic GABAergic synapses using dual whole-cell patch clamp recordings in layer 2/3 of human neocortex. We found that activation of group I mGluRs by the agonist DHPG had diverse effects on excitatory synaptic strength. In most cases we either observed potentiation or no significant change. A subset of of interneurons showed significant depression of synaptic strength. Parallel experiments in Wistar rats showed DHPG-mediated strengthening of glutamatergic input to fast-spiking basket cells. A uniquely human feature of cortical computation is that a single action potential in a pyramidal cell can elicit a subthreshold response in their postsynaptic interneuron initiating polysynaptic network events that can last for tens of milliseconds. Thus we elicited disynaptic inhibitory events and found that a subset of GABAergic connections potentiate upon DHPG application while the majority show no significant changes in strength. Our results demonstrate the diverse synaptic strength modulation of group I mGluRs both in glutamatergic synapses arriving onto interneurons and GABAergic synapses originating from them suggesting a cell type-specific mechanisms of action in the human neocortex.

Unique ID: fens-24/group-metabotropic-glutamate-receptor-mediated-05c3e5f6