Biology subjects

Grosmark, A. D.

Publications and source records attributed to Grosmark, A. D..

4 recordsLinked to original sources

bioRxiv2022

Adult born hippocampal granule cells promote pattern separation by bidirectionally modulating the remapping of place and cue cells.

The hippocampal dentate gyrus (DG) exhibits a unique form of neural plasticity that results from continuous integration of adult born neurons, referred to as adult neurogenesis. Recent studies have proposed that adult neurogenesis promotes the ability to encode new memories without interference from previously stored memories that share similar features, through a neural computation known as pattern separation. However, due to lack of in vivo physiological evidence, the manner in which adult neurogenesis contributes to pattern separation remains unknown. Here, we investigate the contribution of functionally integrated yet immature adult born granule cells (iGCs) to DG computations by examining how chronic ablation or acute chemogenetic silencing of iGCs affects the activity of mature granule cells (mGCs) using in vivo 2-photon Ca2+ imaging. In both cases we observed altered remapping of mGCs but in opposite directions depending on their tuning selectivity. Rather than broadly modulating the activity of all mGCs, iGCs promote the remapping of place cells but limit the remapping of mGCs representing sensory cues (cue cells). We propose that these properties of iGCs explain their role in pattern separation because they promote the formation of non-overlapping representations for identical sensory cues encountered in different locations. Conversely, the absence of iGCs shifts the DG network to a state dominated by sensory cue information, a situation that is consistent with the overgeneralization often observed in anxiety disorders such as PTSD.

neuroscience↗

bioRxiv2021

E-Cannula reveals anatomical diversity in sharp-wave ripples as a driver for the recruitment of distinct hippocampal assemblies

The hippocampus plays a critical role in spatial navigation and episodic memory. However, research on in vivo hippocampal activity dynamics has mostly relied on single modalities such as electrical recordings or optical imaging, with respectively limited spatial and temporal resolution. This technical difficulty greatly impedes multi-level investigations into network state-related changes in cellular activity. To overcome these limitations, we developed the E-Cannula integrating fully transparent graphene microelectrodes with imaging-cannula. The E-Cannula enables the simultaneous electrical recording and two-photon calcium imaging from the exact same population of neurons across an anatomically extended region of the mouse hippocampal CA1 stably across several days. These large-scale simultaneous optical and electrical recordings showed that local hippocampal sharp wave ripples (SWRs) are associated with synchronous calcium events involving large neural populations in CA1. We show that SWRs exhibit spatiotemporal wave patterns along multiple axes in 2D space with different spatial extents (local or global) and temporal propagation modes (stationary or travelling). Notably, distinct SWR wave patterns were associated with, and decoded from, the selective recruitment of orthogonal CA1 cell assemblies. These results suggest that the diversity in the anatomical progression of SWRs may serve as a mechanism for the selective activation of the unique hippocampal cell assemblies extensively implicated in the encoding of distinct memories. Through these results we demonstrate the utility of the E-Cannula as a versatile neurotechnology with the potential for future integration with other optical components such as green lenses, fibers or prisms enabling the multi-modal investigation of cross-time scale population-level neural dynamics across brain regions.

neuroscience↗

bioRxiv2020

Offline Memory Reactivation Promotes the ConsolidationOf Spatially Unbiased Long-Term Cognitive Maps

Spatial memories which can last a lifetime are thought to be encoded during online periods of exploration and subsequently consolidated into stable cognitive maps through their offline reactivation1-5. However, the mechanisms and computational principles by which offline reactivation stabilize long-lasting spatial representations remain poorly understood. Here we employed simultaneous fast calcium imaging and electrophysiology to track hippocampal place cells over weeks of online spatial reward learning behavior and offline resting. We describe that recruitment to persistent network-level offline reactivation of spatial experiences predicts cells future multi-day representational stability. Moreover, while representations of reward-adjacent locations are generally more stable across days, reactivation-related stabilization is, conversely, most prominent for reward-distal locations. Thus, while occurring on millisecond time-scales, offline reactivation counter-balances the observed multi-day representational reward-adjacency bias, promoting the stabilization of cognitive maps which comprehensively reflect entire underlying spatial contexts. These findings suggest that post-learning offline-related memory consolidation plays complimentary and computationally distinct role in learning as compared to online encoding.

neuroscience↗

bioRxiv2020

Parallel processing of sensory cue and spatial information in the Dentate Gyrus

During exploration, animals form an internal map of an environment by combining information about specific sensory cues or landmarks with the animals motion through space, a process which critically depends on the mammalian hippocampus. The dentate gyrus (DG) is the first stage of the hippocampal trisynaptic circuit where self-motion and sensory cue information are integrated, yet it remains unknown how neurons within the DG encode both cue related ("what") and spatial ("where") information during cognitive map formation. Using two photon calcium imaging in head fixed mice running on a treadmill, along with on-line sensory cue manipulation at specific track locations, we have identified robust sensory cue responses in DG granule cells largely independent of spatial location. Granule cell cue responses are stable for long periods of time, selective for the modality of the stimulus and accompanied by strong inhibition of the firing of other active neurons. At the same time, there is a smaller fraction of neurons whose firing is spatially tuned but insensitive to the presentation of nearby cues, similar to traditional place cells. These results demonstrate the existence of "cue cells" in addition to the better characterized "place cells" in the DG, an important heterogeneity that has been previously overlooked. We hypothesize that the granule cell population may support multiple channels of spatial and non-spatial information that contribute distinctly to local and down-stream computations and impact the role of the dentate gyrus in spatial navigation and episodic memory.

neuroscience↗