My career goal is to lead a research group investigating the synaptic and circuit mechanisms underlying cognitive decline during normal aging and in aging-related disorders like dementia and Alzheimer's disease. For this K01, I will specifically address the role of hippocampal neurogenesis?or lack thereof?in aging-related decline in behavioral pattern separation. Deficits in behavioral pattern separation manifest as a tendency to lump similar experience together and confuse memories, both core symptoms of aging-related cognitive decline and dementia. I will employ a vertical approach determine the impact of increasing neurogenesis on behavioral pattern separation and underlying hippocampal mechanisms using behavioral, targeted genetics, electrophysiological, and in vivo 2-photon calcium imaging techniques. These studies represent a number of firsts in the aging neuroscience field: 1) the first to test the controversial hypothesis that neurogenesis accounts for aging-related cognitive decline; 2) the first to test the therapeutic potential of targeting neurogenesis to ameliorate cognitive deficits during aging; 3) the first to investigate the impact of neurogenesis on hippocampal information processing during aging; and 4) the first to use in vivo 2-photon imaging to assess neuronal population coding during behavior in aged mice. These studies represent a significant career change and research redirection for me. This K01 award will thus afford me the protected time and mentorship to acquire the technical and conceptual skills to successfully achieve my career goals.
Aging is the major risk factor for all forms of dementia, most notably Alzheimer's disease. The studies in this K01 proposal will assess the therapeutic potential of targeting hippocampal neurogenesis to ameliorate symptoms of cognitive decline during aging. These studies will also identify novel synaptic and circuit mechanisms that could be exploited to alleviate aging-related cognitive impairments.
|Jimenez, Jessica C; Su, Katy; Goldberg, Alexander R et al. (2018) Anxiety Cells in a Hippocampal-Hypothalamic Circuit. Neuron 97:670-683.e6|
|Anacker, Christoph; Luna, Victor M; Stevens, Gregory S et al. (2018) Hippocampal neurogenesis confers stress resilience by inhibiting the ventral dentate gyrus. Nature 559:98-102|