Role of GABAergic interneuron types in context and rule representation in the medial frontal cortex investigated with 1P-imaging in the freely moving mouse

• Applicant: Professorin Dr. Ilka Diester
• Subject Area: Cognitive, Systems and Behavioural Neurobiology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 513977628

The prefrontal cortex plays a key role in representations of cognitive parameters, including task relevant sensory cues, attention, action selection, and task rules. However, how GABAergic inhibitory interneuron (IN) types contribute to the formation and stabilization of the representation of contexts and rules in active cell assemblies is little understood. We aim to address this fundamental question in the mouse medial prefrontal cortex (mPFC), the cognitive hub of the brain, for the following reasons: 1. Pyramidal cells (PCs), which represent the majority of cells in all cortical areas, are tightly controlled by GABAergic inhibitory INs. 2. Fast-spiking neurons (putatively GABAergic INs) within the PFC have been described to show context-selective activity, while regular spiking cells (putatively glutamatergic PCs) play a major role in rule representation. 3. Parvalbumin (PV) and somatostatin (SOM)-expressing INs (PVIs, SOMIs) have been found to fulfil differential roles in working memory and spatial representations. 4. INs receive direct input from deep subdivisions of CA1 PCs, a highly active place coding population. Building on this knowledge, we aim to examine how PVIs and SOMIs influence the activity of single cells and cell assemblies in the mouse mPFC during context and rule representation. We will address this fundamental topic by applying single photon calcium imaging of prefrontal neuron populations in freely moving mice, and by manipulating PVI and SOMI activity with optogenetic tools. With these results we aim elucidate the circuit mechanisms underlying contextual and rule representations conducted by interneurons in the mPFC. Thus, our major goal is to examine how INs, particularly PVIs/SOMIs, influence the activity of individual PCs and PC assemblies representing rules and contexts in the mPFC. This project will provide new insights on the role of IN types supporting high-level representations in the mPFC.

• DFG Programme: Research Grants