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Erwin, Sarah Rae

University of British Columbia

Subiculum pyramidal neurons form the main output of the hippocampus and are studied as the cellular basis of various aspects of memory and spatial navigation. Increasing evidence has demonstrated a great deal of heterogeneity within the subiculum, from intrinsic cell properties to connectivity and function. Recent single-cell RNA sequencing analysis has identified a sparse, transcriptomically distinct population of subiculum excitatory neurons, marked by high expression of the gene Ly6g6e. Utilizing a transgenic mouse line that allows cre-mediated cell-type-specific access of these cells, this research investigates the morphology, connectivity, and activity correlates of this unique subpopulation. Leveraging this transgenic line with cell-type-specific viral tracing tools and whole brain clearing, we discovered that this neuronal population occupies the deepest layer of the subiculum, displays unique morphological properties, and forms dedicated axonal projections to the anterior thalamic nuclei. Publicly available neuron reconstructions also recapitulate these results. To interrogate potential functional correlates of this population, chemogenetic activity silencing was used during encoding of a novel object recognition (NOR) task. DREADDs-based inhibition of this subpopulation did not produce a behavioral deficit, and histological analysis of activity inhibited cells via fluorescent in situ hybridization (FISH) did not result in decreased immediate early gene (IEG) expression after novel object interaction compared to controls. Considering these results alongside other data from our lab suggests that other methods of manipulating cellular activity may be more suitable for this subpopulation. Motivated by the unique local and long-range structure of this excitatory population and the sustained activity responses seen in vivo, FISH was used to assess potential preferential recruitment of deep subiculum cells via IEG expression following a NOR task. No significant difference in IEG expression was seen between object types; however, this population exhibited a high baseline of activity relative to population abundance. In sum, this data provides evidence for a previously unknown excitatory cell subtype within the subiculum that exhibits unique structural characteristics and sustained activity, and that could play a potentially specialized role in recognition memory.

Text; Moving Image

2024-01-08

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/87148

Neuroscience

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/