One of the core missions in neuroscience is to understand how neuronal activities carry information to guide behavior. A direct approach is to simultaneously record large-scale neural activity in vivo while animal freely performs behavioral tasks. Such measurement could establish detailed mechanisms by which activity of individual neurons or neural ensembles codes animal?s behavior. The development of miniature fluorescence microscope (miniScope) opens up new avenues for obtaining large-scale in vivo neural calcium imaging from freely behaving mice, to elucidate the function and dysfunction of neural circuitry in health and diseases. The long-term goal of the proposed work is to develop and to apply cutting-edge miniScope imaging technique to study neural circuit mechanisms of depression, autism, and dementia in the medial prefrontal cortex (mPFC). This proposal has the following two specific aims:
Aim#1. To elucidate how dysfunctional mPFC neural circuits contribute to social behavior deficits in depression, autism, and dementia. Human patients of depression, autism, and dementia all display deficits in social behavior. To unravel the underlying circuit mechanisms leading to social behavior deficits in these brain disorders, miniScope imaging approach will be employed to examine mPFC neural circuitry in mouse models of depression, autism, and frontotemporal dementia.
Aim#2 : To develop dual-color miniScopes to advance neural circuitry studies. A new version of miniScope with dual LED and a liquid lens will be developed. This new miniScope will enable not only dual-color calcium imaging from both principle neurons and inhibitory interneurons, but also optogenetic manipulation of interneurons and concurrent calcium imaging from principle neurons.
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