Biology subjects

GoodSmith, D.

Publications and source records attributed to GoodSmith, D..

4 recordsLinked to original sources

bioRxiv2025

Learning-Dependent Shift from Right to Left CA3 Input Dominance Shapes the Evolution of Right CA1 Spatial Maps

CA1 place fields support spatial maps critical for memory, yet how bilateral CA3 inputs shape these maps during learning remains unclear. Using two-photon calcium imaging and optogenetic inhibition in head-fixed mice navigating a virtual track, we examined left and right CA3 projections to right CA1 (CA1R) as animals familiarized to a novel environment. CA1R maps were initially inaccurate but stabilized after [~]10 laps, defining an early-phase of map refinement followed by a late-phase of stability. During the early-phase, right CA3 inputs predominantly drove refinement, whereas left CA3 inputs controlled stability later. These effects arose at the single-cell level, with right CA3 inputs driving high-amplitude, reliable fields early and left inputs supporting reliable fields later. Axonal recordings revealed a matching shift: right CA3 axons showed greater place-field activity and reliability early, whereas left CA3 axons became more reliable later. Thus, CA3 input dominance transitions from right to left, coordinating CA1R map refinement and stabilization.

neuroscience↗

bioRxiv2025

Complementary regulation of memory flexibility and stabilization by dentate gyrus granule cells and mossy cells

Accurate memory formation requires hippocampal spatial representations to balance stability, for later recall, with flexibility, to incorporate new information. The dentate gyrus (DG) is essential to memory formation, but the distinct roles of its excitatory cell types, granule cells (GCs) and mossy cells (MCs), remain unclear. To evaluate how GC and MC activity affect hippocampal output, we recorded from CA1 using two-photon calcium imaging as head-fixed mice navigated familiar and novel virtual environments. DREADD-mediated MC inhibition disrupted initial map stabilization, decreasing spatial stability in novel, but not familiar, environments. In contrast, GC inhibition increased map stability in familiar, but not novel, environments by disrupting drift of spatial maps across distinct experiences (episodes) within an environment. These results reveal how distinct DG cell types support hippocampal memory formation in context-dependent ways; MCs promote stabilization of new spatial maps to support accurate memory recall, while GCs promote flexibility to update existing representations.

neuroscience↗

bioRxiv2022

Global remapping in granule cells and mossy cells of the mouse dentate gyrus

Hippocampal place cells exhibit spatially modulated firing, or place fields, which can remap to encode changes in the environment or other variables. Unique among hippocampal subregions, the dentate gyrus (DG) has two excitatory populations of place cells, granule cells and mossy cells, which are among the least and most active spatially modulated cells in the hippocampus, respectively. Previous studies of remapping in the DG have drawn different conclusions about whether granule cells exhibit global remapping and contribute to the encoding of context specificity. By recording granule cells and mossy cells as mice foraged in different environments, we found that by most measures, both granule cells and mossy cells remapped robustly but through different mechanisms that are consistent with firing properties of each cell type. Our results resolve the ambiguity surrounding remapping in the DG and suggest that most spatially modulated granule cells contribute to orthogonal representations of distinct spatial contexts.

neuroscience↗

bioRxiv2021

Flexible encoding of objects and space in single cells of the dentate gyrus

The hippocampus is involved in the formation of memories that require associations among stimuli to construct representations of space and the items and events within that space. Neurons in the dentate gyrus (DG), an initial input region of the hippocampus, have robust spatial tuning, but it is unclear how nonspatial information may be integrated with spatially modulated firing at this stage. We recorded from the DG of 21 adult mice as they foraged for food in an environment that contained discrete objects. By classifying recorded DG cells into putative granule cells and mossy cells, we examined how the addition or displacement of objects affected the spatial firing of these DG cell types. We found DG cells with multiple firing fields at a fixed distance and direction from objects (landmark vector cells) as well as cells that exhibited localized changes in spatial firing when objects in the environment were manipulated. When mice were exposed to a second environment with the same objects, DG spatial maps were completely reorganized, suggesting standard global remapping, and a largely different subset of cells responded to object manipulations. Together, these data reveal the capacity of DG cells to detect small changes in the environment, while preserving a stable spatial representation of the overall context.

neuroscience↗