Project Details
Projekt
Olfactory control of long-range coupling in developing prefrontal-hippocampal-entorhinal networks
Subject Area
Cognitive, Systems and Behavioural Neurobiology
Molecular Biology and Physiology of Neurons and Glial Cells
Molecular Biology and Physiology of Neurons and Glial Cells
Term
from 2016 to 2023
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 302153259
While sensory perception and cognitive processing represent constant research topics in Neuroscience, they have seldom been investigated synergistically. This is especially true when considering their ontogeny. Over decades, substantial efforts elucidated the maturation principles of sensory systems by highlighting the relevance of molecular cues, spontaneous electrical activity and experience. More recently, some complex interactions governing the wiring of memory-relevant circuitry during development have been resolved. For example, we recently demonstrated in a collaborative effort that a complex GABA - glutamate interplay generates the hippocampal theta-band driving force that enables the initiation of local circuits in the prefrontal cortex. The largely separate investigation of sensory and cognitive ontogeny stems from the fact that most sensory systems are underdeveloped during early life and, thus, their impact on the formation of neuronal networks underlying cognitive processing has been deemed negligible. As a notable exception, the olfactory system reaches full maturity during intrauterine life, controlling mother-offspring interactions and survival. It is, however, still unknown whether early olfactory inputs drive the development of limbic networks. The goal of the present research proposal is to understand the structural and functional principles underlying the connectivity and communication between the olfactory bulb (OB) and lateral entorhinal cortex (LEC), the gatekeeper of limbic circuitry during neonatal and juvenile development. By elucidating OB - LEC connectivity (aim 1) we aim to provide an anatomical framework for subsequent physiological analysis of olfactory - limbic activity patterns (aim 2). Subsequently, we will investigate the acute and long-term effects of olfactory stimulation on the development of limbic circuits and corresponding cognitive behavior (aim 3). To reach these goals, the project is centered on complementary expertise of the applicants both at a conceptual level, by linking olfactory system physiology (Spehr) with functional development of limbic circuitry (Hanganu-Opatz), and a methodological level, by exploiting novel and highly interdisciplinary experimental strategies that combine trans-synaptic tracing, opto- and pharmacogenetic manipulations with in vitro and in vivo physiology. Given the unique importance of early olfactory input, we hypothesize that a specific spatiotemporal organization of OB activity during neonatal development facilitates the entrainment and refinement of downstream entorhinal-prefrontal-hippocampal networks. On the long-term, our study is designed to provide detailed insight into the physiological principles that link fundamental aspects of sensory and cognitive neurobiology.
DFG Programme
Research Grants
