Cerebellum-dependent learning over different time scales in an Alzheimer's Disease model

Stanford University, Stanford CA

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Abstract

ABSTRACT OF PROPOSED SUPPLEMENT We will characterize cerebellum-dependent learning and memory in the 5XFAD mouse model of Alzheimer?s disease (Oakley et al., 2006), and compare impairments in these mice on different time scales: short-term (seconds, single trial), intermediate-term (tens of minutes, cumulative learning over a single training session) and long-term (days, consolidation). The Alzheimer?s mouse model can help achieve the parent grant?s scientific goal of dissecting the mechanistic relationship between different time scales of cerebellum-dependent learning. Moreover, there is evidence to suggest a role of the cerebellum in Alzheimer?s disease (Larner, 1997; Baloyannis et al., 2000; Ciavardelli et al., 2010; Mavroudis et al., 2010; Lomoio et al., 2012; Hoxha, et al. 2012; Baloyannis et al., 2013; Sepulveda-Falla et al., 2014; Kuwabara et al., 2014; Jacobs et al., 2017), but this is a highly understudied aspect of the disease compared to the role of the forebrain. The oculomotor system provides a sensitive and analytically tractable approach to understand broader learning and memory deficits in Alzheimer?s.