Function of lateral Inhibition in layer 2/3 of adult mouse barrel cortex

• Applicants: Professor Dr. Heiko J. Luhmann; Professor Dr. Maik C. Stüttgen
• Subject Area: Cognitive, Systems and Behavioural Neurobiology
• Term: from 2015 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 280347763

Neocortical layer 2/3 represents the first neuronal station in the somatosensory system which processes incoming sensory information in an integrative manner. In the barrel cortex, these layers represent the first station integrating tactile information from neighbouring whiskers. Therefore, layer 2/3 fulfils an important role in the discrimination of sensory stimuli. The spatio-temporal precision of this discrimination is mostly mediated by intralaminar lateral inhibition, in which parvalbumin-immunoreactive (PV+) GABAergic interneurons with fast spiking (FS) discharge patterns play a central role. Electrophysiological, behavioural and optogenetic methods will be used in the vibrissal system of adult mice to elucidate the function of lateral inhibition in layer 2/3. Two novel behavioural tests will allow the experimental analysis of the spatial and spatio-temporal discrimination capability between mechanical stimuli delivered to two neighbouring vibrissae in head-fixed, operantly conditioned animals. The neuronal activity associated with this discrimination task will be recorded in the corresponding cortical columns with an 80-channel multi-electrode-array. The selective expression of the chloride pump Archaerhodopsin-3 (Arch) in FS-PV+ interneurons via viral transfection (rAAV2/Flex-Arch-GFP) in transgenic mice of the line B6.Cg-Pvalbtm1.1(cre)Aibs/J will allow a specific and local optogenetic manipulation of lateral inhibition in layer 2/3 and the analysis of the resulting behavioural and electrophysiological modifications. The consequence of optogenetic inhibition of FS-PV+ interneurons at the cellular and local network level will be studied in in vitro thalamocortical slice preparations of the barrel cortex. These in vivo and in vitro experiments will yield novel insights to the spatio-temporal properties of lateral inhibition in physiologically relevant tasks.

• DFG Programme: Research Grants