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German Israeli Project Cooperation (DIP) The neurobiology of forgetting - spontaneous synaptic remodeling, cortical representation stability, memory retention and behavioral flexibility

Laufzeit: 01.01.2021 - 31.12.2025

Kurzfassung


The Neurobiology of Forgetting - Spontaneous Synaptic Remodeling, Cortical Representation Stability, Memory Retention and Behavioral Flexibility
Why do we forget? The fascinating phenomenon of forgetting, originally studied by experimental psychologists and later by experimental, computational, and theoretical neuroscientists, has been a focus of research for over a century. Although forgetting is often regarded as detrimental, in particular in association with pathologies such as dementia, we...
The Neurobiology of Forgetting - Spontaneous Synaptic Remodeling, Cortical Representation Stability, Memory Retention and Behavioral Flexibility
Why do we forget? The fascinating phenomenon of forgetting, originally studied by experimental psychologists and later by experimental, computational, and theoretical neuroscientists, has been a focus of research for over a century. Although forgetting is often regarded as detrimental, in particular in association with pathologies such as dementia, we now know that it is crucially important for behavioral flexibility – the adaptation to changing environments or the generalization of acquired knowledge – as well as for mitigating traumatic events. A straightforward possibility - albeit hardly explored - is that spontaneous changes in synaptic connection might drive forgetting. The overall goal of this project is thus to explore relationships between spontaneous synaptic remodeling, forgetting and behavioral flexibility. The major thrust is to (1) devise perturbations that specifically and selectively affect spontaneous synapse remodeling rates; (2) introduce the most effective molecular modifications into mouse models (3) validate their effects on synaptic remodeling dynamics in vivo; (4) examine how these perturbations affect the stability of cortical representations in these animals, and (5) examine by behavioral testing how these perturbations affect memory, forgetting, and behavioral flexibility. To attain this goal, we propose a collaborative, multilevel (molecular, synaptic, network, behavior) program which deeply integrates experimentation, advanced analytical methods and theory.
 
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