Project Details
Projekt
Cognitive performance as result of coordinated neuronal activity within developing prefrontal-hippocampal circuits
Applicants
Dr. Michael Denker; Professorin Dr. Ileana L. Hanganu-Opatz; Professor Dr. Peter Hegemann; Professor Dr. Thomas Oertner
Subject Area
Molecular Biology and Physiology of Neurons and Glial Cells
Term
from 2016 to 2017
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 322093511
The co-activation of prefrontal and hippocampal networks in oscillatory rhythms is critical for precise information flow in mnemonic and executive tasks, yet its role for cognitive ontogeny is still unknown. This knowledge gap is mainly due to the absence of suitable tools for interrogation of developing circuits. Within a collaborative effort of a troika that joins expertise in engineering and validating light-sensitive proteins with neurophysiological and analytical approaches, we elucidated during the 1st funding period of the Priority Program 1665 the cellular substrate of neonatal prefrontal-hippocampal communication and identified key cellular elements of oscillatory coupling. During early development discontinuous theta activity in the hippocampus (HP) drives the local gamma-band synchrony in prefrontal cortex (PFC) via axonal projections. Using novel high-efficiency mutants of channelrhodopsin in combined extracellular and patch-clamp recordings in vivo and in vitro, we activated / silenced the neuronal activity. We identified prefrontal layer II/III pyramidal neurons projecting to layer V neurons as key neurons for the emergence of beta-low gamma oscillations in the neonatal brain. The present project aims at understanding the role of neuronal and network activity in neonatal prefrontal-hippocampal circuits for the maturation of mnemonic and executive abilities. For this, the previously identified key neurons will be silenced during defined developmental time windows using novel light-controlled K+-channels that will be engineered and validated by the troika. Short- and long-term consequences of this selective neuronal manipulation for the connectivity and functional communication (synchrony, spiking patterns, long-range causal interactions) within developing prefrontal-hippocampal networks will be assessed. Moreover, the adult behavioral readout of early manipulation will be characterized to decide on the necessity of coordinated activity during development for the maturation of mnemonic and executive abilities. On the long-term, the results of these investigations will provide detailed insight into the physiological and pathophysiological principles of cognitive ontogeny.
DFG Programme
Priority Programmes
