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.

A06 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.

Letzte Änderung: 09.03.2021 - Ansprechpartner:

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