Linking birthdate with functional diversity in CA1 pyramidal neurons in the awake mouse hippocampus

• Applicant: Dr. Susanne Reichinnek
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells ; Anatomy and Physiology
• Term: from 2014 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 254966771

Cell type diversity classically reflects the available repertoire of neuronal functions in different brain regions. The hippocampus processes multimodal information and is important for spatial and declarative memory function. During spatial exploration, principal cells of all hippocampal subfields are entrained by a theta-nested gamma oscillation, forming transient assemblies of co-active neurons (Buzsaki and Draguhn 2004). These co-active neurons form sequential activation patterns which finally represent the animal´s trajectory through space (OKeefe and Reece 1993). During sleep these sequences are re-activated for consolidation purposes by sharp-wave ripple oscillations (Wilson 1994) . The organization of neuronal assemblies requires a structuring element. Different cell types probably entrain neuronal groups, coordinate state-dependent oscillations and therefore structure the various network functions. So far, cell diversity in the hippocampus seems to be a major hallmark for GABAergic cells (Klausberger 2008). Their activity was shown to be correlated to different network states and is partly rooted in their spatio-temporal embryonic origin. In contrast, only few studies address the possibility that glutamatergic CA1 pyramidal cells may comprise several subtypes with different genetic, morphological and functional features although they represent 80% of the neuronal population. In addition, the Cossart lab has found that an early temporal origin delineates a distinct morpho-functional subtype of glutamatergic neuron in the CA3 region of the hippocampus (Marissal 2012) in vitro.My project aims to understand the relationship between developmental fate and neuronal network dynamics of hippocampal glutamatergic neurons in the hippocampal subfield CA1. My project is based on a transgenic mouse line from the Cossart group (Allene 2012) where the transcription factor Neurogenin2 (Ngn2) permits the labeling of glutamatergic neurons according to their birthdate. I will perform electrophysiological recordings in acute hippocampal slices to characterize basic electrophysiological properties of early-born (embryonic day 11) and late-born (embryonic day 15) neurons in CA1. In addition, I want to determine physiological activity patterns of these cells in awake mice running on a treadmill. Using 2-photon calcium imaging, a stereotactically delivered, genetically-encoded calcium indicator (GCaMP-6) will indicate single action potentials within a single focal plane of the dorsal CA1 subfield. Thereby, I will monitor firing pattern of several pyramidal cells during typical behaviorally-relevant network oscillations (exploration - theta-nested gamma and waking immobility/sleep - sharp wave ripple) and investigate their recruitment into network oscillations.The results will provide important insights into how developmental fate affects network recruitment and network dynamics.

• DFG Programme: Research Fellowships
• International Connection: France
• Host: Professorin Rosa Cossart, Ph.D.