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.
RAYMOND, Jennifer L. PROJECT NARRATIVE Alzheimer's disease is characterized by a progressive loss of memory. This project will analyze the role of a brain region called the cerebellum in perturbations of short-, intermediate- and long-term learning and memory in a mouse model of Alzheimer's disease. OMB No. 0925-0001/0002 (Rev. 01/18 Approved Through 03/31/2020) Page Continuation Format Page
| Suvrathan, Aparna; Payne, Hannah L; Raymond, Jennifer L (2018) Timing Rules for Synaptic Plasticity Matched to Behavioral Function. Neuron 97:248-250 |
| Nguyen-Vu, Td Barbara; Zhao, Grace Q; Lahiri, Subhaneil et al. (2017) A saturation hypothesis to explain both enhanced and impaired learning with enhanced plasticity. Elife 6: |
| Suvrathan, Aparna; Payne, Hannah L; Raymond, Jennifer L (2016) Timing Rules for Synaptic Plasticity Matched to Behavioral Function. Neuron 92:959-967 |
| Katoh, Akira; Shin, Soon-Lim; Kimpo, Rhea R et al. (2015) Purkinje cell responses during visually and vestibularly driven smooth eye movements in mice. Brain Behav 5:e00310 |
| Shin, Soon-Lim; Zhao, Grace Q; Raymond, Jennifer L (2014) Signals and learning rules guiding oculomotor plasticity. J Neurosci 34:10635-44 |
| Kimpo, Rhea R; Rinaldi, Jacob M; Kim, Christina K et al. (2014) Gating of neural error signals during motor learning. Elife 3:e02076 |
| Guo, Christine C; Ke, Michael C; Raymond, Jennifer L (2014) Cerebellar encoding of multiple candidate error cues in the service of motor learning. J Neurosci 34:9880-90 |
| Conner, Alana L; Cook, Karen S; Correll, Shelley J et al. (2014) Obscuring gender bias with ""choice"". Science 343:1200 |
| Nguyen-Vu, T D Barbara; Kimpo, Rhea R; Rinaldi, Jacob M et al. (2013) Cerebellar Purkinje cell activity drives motor learning. Nat Neurosci 16:1734-6 |
| Guo, Cong C; Raymond, Jennifer L (2010) Motor learning reduces eye movement variability through reweighting of sensory inputs. J Neurosci 30:16241-8 |
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