Project Details
Projekt
Die Rolle der Plastizität von Interneuronen bei der inhibitorischen Kontrolle von Zielbewegungen
Applicant
Professor James F.A. Poulet, Ph.D.
Subject Area
Molecular Biology and Physiology of Neurons and Glial Cells
Term
from 2014 to 2022
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 245861656
Little is known about how the plasticity of excitatory input to neocortical GABAergic inhibitory interneurons (INs) is linked to network activity and voluntary behavior. We address this question in layers 2/3 and 5 of the primary motor forelimb cortex (M1) of mice during learning a novel cortically-dependent, sensory-triggered, reaching task. Preliminary extracellular and whole-cell recordings of parvalbumin-expressing perisomatic inhibitory interneurons (PVIs) and regular spiking, excitatory, neurons in naïve, untrained, awake mice show that vibrotactile stimulation of the forepaw triggers an excitatory response in M1 neurons, but no forelimb movement. In trained mice, however, this response is rapidly transformed into a reaching motor command that scales with the distance reached. Intriguingly, the excitatory movement command in PVIs occurs before that in excitatory neurons, moreover optogenetic stimulation of M1 PVIs can evoke complete reaches. Together our data suggests that, rather than inhibiting motor output as proposed by classic models of M1 function, excitatory input to PVIs and subsequent PVI spiking is involved in the release of voluntary movements. Here, our goal is to test the hypothesis that plasticity of excitatory inputs to M1 PVIs during learning drives the recruitment of PVI-evoked reaching. We will perform extracellular and 2-Photon (2P) targeted recordings alongside optogenetic manipulations of PVIs and somatostatin-expressing dendritic inhibitory INs (SOMIs) before and after learning to reach. Moreover, we will use molecular tools developed and tested from our collaborators in the research unit (RU) to mark and manipulate those INs undergoing plasticity to directly link IN plasticity to M1 circuit dynamics and reaching.
DFG Programme
Research Units
