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Lee, J. Q.

Publications and source records attributed to Lee, J. Q..

5 recordsLinked to original sources

Representations in the hippocampal-entorhinal system emerge from learning sensory predictions

The hippocampal formation and adjacent parahippocampal areas are central to intelligent behaviour such as memory and navigation. Understanding how systems in the brain generate structured representations from experience remains a fundamental goal in neuroscience. A central open question is whether a single computational principle can account for the diverse neural responses observed across the hippocampal-entorhinal circuit. Existing models often rely on hand-crafted features or specialized learning mechanisms unrelated to sensory observations, and typically express representations of only a small subset of known cell types. Further, representations learned in such models are often not empirically evaluated against neural representations observed in the navigating brain. Here, we introduce a neurobiologically-inspired and robust computational model in which diverse cell types emerge from a single learning objective with minimal hand-engineered assumptions. Our model applies contrastive graph representation learning to transitions between high-dimensional visual observations, constructing a metric space in which temporally adjacent sensory observations are mapped to nearby states. Inspired by the anatomical information flow of the hippocampal-entorhinal system, and anchored in output representations based on neural coding in the entorhinal cortex, the model gives rise to activity resembling place cells, grid cells, boundary vector cells, band cells, corner cells, and conjunctive cells among others. Across varied environments and sensory streams, the framework captures not only diverse neural response patterns but also the functional dependencies between them, mirroring the proposed sequential representational structure observed in the hippocampal-entorhinal system. Crucially, place-cell-like features of the model quantitatively reproduce remapping dynamics observed in CA1 of freely moving animals, and afford theoretical explanatory power of existing neurobiologically-informed models. This work thus offers a unified computational model of spatial coding in the hippocampal-entorhinal system and a testable framework for generating mechanistic hypotheses in silico, to be evaluated in vivo.

neuroscience↗

Sparsity of population activity in the hippocampus is task-invariant across the tri-synaptic circuit and dorsal-ventral axis

Evidence from neurophysiological and genetic studies demonstrates that activity sparsity - the proportion of neurons that are active at a given time in a population - systematically varies across the canonical trisynaptic circuit of the hippocampus. Recent work has also shown that sparsity varies across the hippocampal dorsoventral (long) axis, wherein activity is sparser in ventral than dorsal regions. While the hippocampus has a critical role in long-term memory (LTM), whether sparsity across the trisynaptic circuit and hippocampal long axis is task-dependent or invariant remains unknown. Importantly, representational sparsity has significant implications for neural computation and theoretical models of learning and memory within and beyond the hippocampus. Here we used functional molecular imaging to quantify sparsity in the rat hippocampus during performance of the Morris water task (MWT) and contextual fear discrimination (CFD) - two popular and distinct assays of LTM. We found that activity sparsity is highly reliable across memory tasks, wherein activity increases sequentially across the trisynaptic circuit (DG < CA3 < CA1) and decreases across the long axis (ventral < dorsal). These results have important implications for models of hippocampal function and suggest that activity sparsity is a preserved property in the hippocampal system across cognitive settings.

neuroscience↗

Social valence dictates sex differences in identity recognition

Social valence is the directional emotional significance affiliated with social experiences. Maladaptive processing of negative social valence (NSV) has been linked to mood disorder susceptibility, which is more prevalent in women. To determine whether there are sex differences in NSV processing, we developed social valence tasks where the identity recognition of conspecifics with distinct valences served as the readout. Male mice demonstrated identity recognition regardless of social valence. Conversely, female mice did not show identity recognition following the NSV task. In vivo calcium imaging of the dorsal CA1 further revealed sex differences in NSV processing with reduced hippocampal representation of social information in female mice. These results suggest the imprecise encoding of NSV may contribute to the heightened vulnerability to social stress-related mood disorders in women.

neuroscience↗

Identifying representational structure in CA1 to benchmark theoretical models of cognitive mapping

Decades of theoretical and empirical work have suggested the hippocampus instantiates some form of a cognitive map. Yet, tests of competing theories have been limited in scope and largely qualitative in nature. Here, we develop a novel framework to benchmark model predictions against observed neuronal population dynamics as animals navigate a series of geometrically distinct environments. In this task space, we show a representational structure in the dynamics of hippocampal remapping that generalizes across brains, discriminates between competing theoretical models, and effectively constrains biologically viable model parameters. With this approach, we find that accurate models capture the correspondence in spatial coding of a changing environment. The present dataset and framework thus serve to empirically evaluate and advance theories of cognitive mapping in the brain. HIGHLIGHTSO_LIWe identify representational structure in CA1 remapping that is reliable across brains. C_LIO_LIWe directly compare models of cognitive mapping to this representation in CA1. C_LIO_LIModels based on local boundary distance and direction predict CA1 representation. C_LIO_LIThis approach reveals a biologically viable parameter space for model predictions. C_LIO_LIAccurate models capture the correspondence of spatial codes across environments. C_LI

neuroscience↗

Behaviour-driven Arc expression is greater in dorsal than ventral CA1 regardless of task or sex differences.

Evidence from genetic, behavioural, anatomical, and physiological study suggests that the hippocampus functionally differs across its longitudinal (dorsoventral or septotemporal) axis. Although, how to best characterize functional and representational differences in the hippocampus across its long axis remains unclear. While some suggest that the hippocampus can be divided into dorsal and ventral subregions that support distinct cognitive functions, others posit that these regions vary in their granularity of representation, wherein spatial-temporal resolution decreases in the ventral (temporal) direction. Importantly, the cognitive and granular hypotheses make distinct predictions on cellular recruitment dynamics under conditions when animals perform tasks with qualitatively different cognitive-behavioural demands. The cognitive function account implies that dorsal and ventral cellular recruitment differs depending on relevant behavioural demands, while the granularity account suggests similar recruitment dynamics regardless of the nature of the task performed. Here, we quantified cellular recruitment with the immediate early gene (IEG) Arc across the entire longitudinal CA1 axis in female and male rats performing spatial- and fear-guided memory tasks. Our results show that recruitment is greater in dorsal than ventral CA1 regardless of task or sex. This experimentum crucis leads to the strong inference that the granularity hypothesis for functional differences across the longitudinal axis in the rodent hippocampus is correct.

neuroscience↗