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Abstract Details

Differential Reductions of in vivo Activity in CA1 Pyramidal Neuron Subpopulations during Spatial Working Memory in the 5xFAD Model of Amyloidosis
Aging, Dementia, and Behavioral Neurology
P5 - Poster Session 5 (8:00 AM-9:00 AM)
3-008
We compared markers of neuronal activity elicited during spatial working memory in the 5xFAD amyloidosis model versus WT mice across subpopulations of dorsal hippocampal CA1 defined by neuronal location along the radial (superficial, deep) and transverse (CA1a, CA1c) axes.

Pyramidal neurons of CA1 are impacted early in Alzheimer disease (AD) to affect memory. The circuit basis of this memory deficit is unclear. Prior research suggests that CA1 contains genetically and functionally heterogeneous pyramidal neuron populations. For example, location-dependent activity becomes increasingly robust from CA1a (near subiculum) to CA1c (near CA2), and in deep (dPN) versus superficial (sPN) pyramidal neurons. We hypothesized that activity changes due to amyloidosis would also vary across these subpopulations.
A cohort of 5xFAD and WT mice (n = 8-10 female/group, 6-10 mo old) underwent the Y-maze spatial working memory assay. After behavior, immunohistochemical strategies were applied to quantify neuronal c-Fos expression, a marker of neuronal activity, in CA1 across radial and transverse axes. The c-Fos counts were normalized by the number of neurons per subpopulation observed by DAPI stain.
Compared to WT, in 5xFAD mice there was a 30% reduction in the activity of CA1a (p = 0.0084) and CA1c dPN’s (p = 0.0004).  There were no other statistically significant activity reduction across genotype in the other CA1 subpopulations.
Spatial working memory deficits in 5xFAD mice arise from dysfunction of the dPN subpopulation. This promotes further work on elucidating how amyloid impacts memory in a cell type-specific manner.
Authors/Disclosures
Dylan J. Rhodes, BS
PRESENTER 		Mr. Rhodes has nothing to disclose.
Isabel Reyes Isabel Reyes has nothing to disclose.
Chengju Tian Chengju Tian has nothing to disclose.
Mohankumar Thangavel (NYU Grossman School of Medicine) Mohankumar Thangavel has nothing to disclose.
Arjun V. Masurkar, MD (NYU Langone Medical Center) The institution of Dr. Masurkar has received research support from NIH. The institution of Dr. Masurkar has received research support from Alzheimer's Association. The institution of Dr. Masurkar has received research support from BrightFocus Foundation. Dr. Masurkar has received personal compensation in the range of $500-$4,999 for serving as a IRGP Advisory Council Member with Alzheimer's Association. Dr. Masurkar has a non-compensated relationship as a Steering Committee Member with Alzheimer's Disease Cooperative Study that is relevant to AAN interests or activities.