Visualizing and manipulating cell-type-specific spatial and non-spatial memory in the subiculum

Classically, pyramidal cells of the hippocampus are viewed as flexibly representing spatial and non-spatial information. Recent work has illustrated distinct types of hippocampal excitatory cells, suggesting that hippocampal representations and functions may be constrained and interpreted by these underlying cell-type identities. This thesis reveals a non-pyramidal excitatory cell type - the “ovoid” cell - that is spatially adjacent to subiculum pyramidal cells but differs in gene expression, electrophysiology, morphology, and connectivity. In vivo calcium imaging revealed slow, sustained activity in response to non-spatial novel object encounters, with minimal responses to spatial changes such as object relocation or environmental context shifts. These novelty-driven responses persisted longitudinally, with familiar objects failing to drive activity even months after single-trial learning, suggesting a cellular “memory” of objects novelty that lasts for months. Optogenetic experiments confirmed a causal role wherein silencing ovoid cells during encoding impaired object recognition, while activation during retrieval biased behaviour toward familiar stimuli. This work reveals that not all excitatory hippocampal cells serve flexible, general-purpose roles. Instead, ovoid cells exemplify how molecularly defined subtypes can perform distinct, specialized functions in memory processing, establishing a new framework for understanding how subicular cell-type diversity supports a diverse range of functions and roles in behaviours.