Project Details
Projekt
GABAB receptor-mediated regulation of synaptic plasticity in interneurons
Applicant
Professor Dr. Imre Vida
Subject Area
Molecular Biology and Physiology of Neurons and Glial Cells
Term
from 2014 to 2023
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 245861656
The goal of this project is to identify the role of GABAB receptors (GABABRs) in the mediation and modulation of synaptic plasticity in GABAergic inhibitory interneurons (INs). GABABRs act as major regulator of plasticity in principal cells. Although there are multiple sites of action with divergent effects, as a net effect, their activation promotes Hebbian long-term potentiation (LTP) in excitatory principal cell networks. However, INs are highly diverse and their synaptic and intrinsic properties are markedly different to those of principal cells. Therefore GABABRs are expected to have different impact in the various IN types. Consistent with this hypothesis, in the last funding period we found that GABABRs show differential expression and functional effects in pre- and postsynaptic compartments of distinct IN types. We further found that GABABR activation inhibits, rather than facilitates, Hebbian plasticity at excitatory glutamatergic synapses onto somatostatin (SOM)-expressing INs (SOMIs) and parvalbumin (PV)-expressing INs (PVIs). In continuation of this work (1) we aim to investigate the cellular and subcellular distribution of GABABRs in the diverse types of cortical INs in collaboration with TP4 Kulik. (2) We will analyze the cellular and molecular mechanisms underlying the inhibitory effects of GABABRs on synaptic plasticity at excitatory glutamatergic synapses onto INs in close interaction with TP1 Bartos, TP2 Geiger and TP5 Wulff. (3) Investigate the involvement and relevance of GABABR-mediated signalling in functional and structural plasticity of GABAergic output synapses of distinct IN types in collaboration with TP1 Bartos and TP4 Kulik. (4) We will assess whether GABABR-mediated signalling itself can undergo long-term plasticity in INs in parallel to plastic changes at their excitatory inputs in collaboration with TP4 Kulik. Such plasticity could enhance the efficacy and dynamic range of GABABR effects in the control of IN recruitment. Finally, (5) we will develop microcircuit and small-scale network models to analyze the impact of these forms of plasticity for network dynamics in interaction with TP1 Bartos, TP2 Geiger and TP9 Sprekeler. To address these questions we will apply a combination of in vitro electrophysiological, neuroanatomical and computational techniques focusing on two major types of INs, perisomatic-inhibitory PV-positive basket cells (BCs), and dendritic-inhibitory SOM-expressing oriens-lacunosum-moleculare (O-LM) INs. In this project we expect to find cell type- and region specific divergence in the GABABR-mediated modulation of synaptic plasticity and thereby obtain a better understanding of the functional diversity of INs in terms of network state and GABAergic modulation with implications for cognitive functions, as well as disease states of the brain.
DFG Programme
Research Units
