The role of dentate gyrus interneuron plasticity in the representation of location, environment and objects

• Applicant: Professorin Dr. Marlene Bartos
• Subject Area: Cognitive, Systems and Behavioural Neurobiology ; Experimental and Theoretical Network Neuroscience
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 521666973

How information is processed and represented in the brain to enable individual organisms to adapt behavior to their continuously changing environment is a fundamental building block of current neuroscience. However, little progress has been made on how memory traces emerge in neuronal networks during learning. Current theories propose that during learning modifications of synaptic weights enable a selected group of principal cells (PCs) to form a new cell association, which represents the new information. However, how these cell associations emerge across time and how GABAergic inhibitory interneurons may contribute to this process is largely unknown. We hypothesise that synaptic plasticity at excitatory glutamatergic inputs onto interneurons (INs) supports their recruitment and thereby markedly contribute to memory trace formation. Here, we aim to address this hypothesis on somatostatin (SOM) expressing interneurons (SOMIs) of the dentate gyrus (DG) targeting distal dendrites of local granule cells (GCs), the PCs of this brain area. We recently identified group I metabotropic glutamate receptor 1 (mGluR1) and mGluR5 as key molecular mechanisms underlying the emergence of synaptic plasticity at GC-mediated synapses onto SOMIs. (1) Here, we aim to perform whole-cell recordings in acute hippocampal slice preparations to examine the major molecular cascades downstream of mGluR1 underlying plasticity induction at GC-SOMI synapses and compare them with our already published ones for GC synapses targeting parvalbumin (PV)-expressing interneurons. (2) We aim to apply our recently tested small hairpin RNA (shRNA) interference tools for mGluR1 knockdown, to examine the impact of lost SOMI input plasticity on neuronal network dynamics. We will us 2-photon imaging in the DG of head-fixed mice navigating through a virtual reality on a liner track searching for rewards and 1-photon imaging of freely moving mice performing a DG-dependent object-recognition task. (3) We will apply population-vector based decoder analysis of population activity obtained on the linear track and during free spatial exploration to examine the impact of IN plasticity on the encoding of the current location, the environment and memorized objects. Thus, the major goal of the proposed project is to examine how SOMI plasticity influences activity dynamics of GC assemblies encoding information about space, context (where?) and objects within an environment (what?). This project will contribute to our understanding on the role of IN input plasticity in memory. We believe that this work is clinically relevant, since deficits in IN function are hallmarks of cognitive diseases.

• DFG Programme: Research Grants