PP 1665: Optogenetic Dissection of the Developing Prefrontal-Hippocampal Circuitry That Gates Mnemonic and Executive Maturation

Processing and integration of information within neuronal networks accounts for mnemonic and executive abilities. The relevance of these functional interactions is exemplified in the case of the prefrontal cortex (PFC) and hippocampus (HP). Entrainment of both areas in oscillatory rhythms ensures the spatio-temporal orchestration of neuronal activity and enables information transfer and storage. The oscillatory coupling within prefrontal-hippocampal networks emerges during early neonatal development, with discontinuous theta activity in the HP driving the local gamma-band synchrony in the PFC via axonal projections. However, the cellular elements critically underlying the functional communication within developing prefrontal-hippocampal networks and the net impact of early network entrainment on the later cognitive abilities remain unknown. The present project aims at elucidating these issues within a collaborative effort of a “troika” by combining the engineering of new optogenetic tools and development of analytic approaches with in vivo and in vitro electrophysiology as well as behavioural investigation. Fast-light-activation and silencing of different neuronal subtypes will be achieved at two different wavelengths after delivering by regionspecific in utero electroporation newly designed push-pull tandem constructs that contain mutated channelrhodopsins and inhibitory ion pumps. Recordings of the local field potential (LFP) and multiple unit activity (MUA) in the neonatal PFC and HP using optoelectrodes in vivo followed by synchrony analysis at the spike and population levels will determine the neuronal subtypes (“key neurons”), critically causing prefrontal network oscillations in different frequency bands and the cellular mechanisms of prefrontal-hippocampal communication during early development. To ascertain the long-term functional and behavioural readout of light-activation/silencing of key neurons, optogenetic tools for extended depolarization and hyperpolarization will be designed by Two Component Optogenetic (TCO) and activated during defined periods of development. Their impact on the oscillatory entrainment and directed interactions within prefrontal-hippocampal networks will be assessed by in vivo extracellular recordings from freely moving pups during accomplishment of cognitive tasks. The results of these investigations will yield novel insights into the causal relationships between early neuronal activity and correct wiring of developing networks underlying cognitive processing at adulthood.

Principal Investigators
Hegemann, Peter Prof. Dr. (Details) (Experimental Biophysics)

Duration of Project
Start date: 09/2013
End date: 12/2021

Research Areas
Cognitive Neuroscience, Systemic Neuroscience, Computational Neuroscience, Behaviour

Last updated on 2021-15-09 at 11:48