A06 - Neural resource mediated by BDNF-dependent neuroplasticity of cortico-hippocampal interactions
|
Neuronal interactions between the hippocampus (HIP) and prefrontal cortex (PFC) mediate essential cognitive brain functions including spatial learning and fear extinction. This project will study how performance deficits due to pathophysiological or ageing-dependent malfunction in one of the two brain areas can be ameliorated by BDNF release-dependent compensatory re-shaping of HIP-PFC synaptic circuits. We hypothesise that the HIP-PFC synaptic circuit provides a platform to serve as a neural resource that can be tuned by BDNF-dependent mechanisms and exploited as a neural reserve during age- or disease-related malfunctioning. To test this, we will employ optogenetically controlled BDNF release in separate experiments in HIP and PFC neurons, respectively, and investigate in a combined in vivo and ex vivo approach (1) the mechanisms of HIP-PFC neuronal interactions that provide the compensatory neural reserve/resource and (2) how unlocking this resource can improve cognitive functions in adult, healthy, aged, and diseased mice. |
|
 |
Conceptual framework of the project. The hippocampus (HIP) and prefrontal cortex (PFC) are bidirectionally connected via direct (solid arrow) and indirect (curved arrow) projections. We are investigating recruitment of this neuronal interaction as a potential implementation of a neural resource/ reserve mechanism by which malfunction in one brain area can be ameliorated by the other area. We propose BDNF-dependent neuronal plasticity as a potential interventional strategy to recruit this reserve in suitable mouse models. We use state-of-the-art techniques for in vivo and ex vivo analysis of HIP and PFC. |