Entry Date:
August 4, 2014

Neuronal Networks, Optogenetics, and Neurodegeneration

Principal Investigator Li-Huei Tsai


To better understand how disease genes and/or pathology impact cognitive function in disorders such as AD and autism, we have aspired to alter the activity of specific neuronal circuits and to evaluate the consequences on pathology, network activity, and behavior. The use of optogenetics allows for the manipulation of specific populations of neural cells in the brain. We have examined the effect of the stimulation or inhibition of specific cells within hippocampal, basal forebrain, and amygdalar circuits upon neurodegeneration and cognitive deficits. We continue to probe potential network dysfunction associated with neurodegeneration and other brain disorders, and to elucidate the contribution of various brain circuits in the early stage of pathogenesis in AD. In addition to the manipulation of specific circuits, we wish to map out which neural circuits are first disrupted by the deposition of Ab peptides and aggregated Tau protein in AD, and how Ab and Tau pathology propagates throughout the brain.

Current work also involves mapping various AD related pathology in a 3-D manner in mouse and human brains. We are using improved CLARITY techniques to interrogate the relationship of b-amyloid plaques, Tau tangles, neural inflammation and vasculature pathology in 3 different mouse models of AD and in postmortem human brain samples of AD subjects. We will also use this approach to assess how environmental enrichment and HDACi treatment, previously shown to improve cognitive function of AD mouse models, influence neuronal circuitry necessary for memory formation and retrieval.