Rashid, S. K. | bioRxiv Science

bioRxiv2023

Entorhinal cortex glutamatergic and GABAergic projections bidirectionally control discrimination and generalization of hippocampal representations

Discrimination and generalization are crucial brain-wide functions for memory and object recognition that utilize pattern separation and completion computations. Circuit mechanisms supporting these operations remain enigmatic. We show lateral entorhinal cortex glutamatergic (LECGLU) and GABAergic (LECGABA) projections are essential for object recognition memory. Silencing LECGLU during in vivo two-photon imaging increased the population of active CA3 pyramidal cells but decreased activity rates, suggesting a sparse coding function through local inhibition. Silencing LECGLU also decreased place cell remapping between different environments validating this circuit drives pattern separation and context discrimination. Optogenetic circuit mapping confirmed that LECGLU drives dominant feedforward inhibition to prevent CA3 somatic and dendritic spikes. However, conjunctively active LECGABA suppresses this local inhibition to disinhibit CA3 pyramidal neuron soma and selectively boost integrative output of LEC and CA3 recurrent network. LECGABA thus promotes pattern completion and context generalization. Indeed, without this disinhibitory input, CA3 place maps show decreased similarity between contexts. Our findings provide circuit mechanisms whereby long-range glutamatergic and GABAergic cortico-hippocampal inputs bidirectionally modulate pattern separation and completion, providing neuronal representations with a dynamic range for context discrimination and generalization.

neuroscience↗

bioRxiv2020

The dendritic spatial code: branch-specific place tuning and its experience-dependent decoupling

Dendrites of pyramidal neurons integrate different sensory inputs, and non-linear dendritic computations drive feature selective tuning and plasticity. Yet little is known about how dendrites themselves represent the environment, the degree to which they are coupled to their soma, and how that coupling is sculpted with experience. In order to answer these questions, we developed a novel preparation in which we image soma and connected dendrites in a single plane across days using in vivo two-photon microscopy. Using this preparation, we monitored spatially tuned activity in area CA3 of the hippocampus in head-fixed mice running on a linear track. We identified "place dendrites", which can stably and precisely represent both familiar and novel spatial environments. Dendrites could display place tuning independent of their connected soma and even their sister dendritic branches, the first evidence for branch-specific tuning in the hippocampus. In a familiar environment, spatially tuned somata were more decoupled from their dendrites as compared to non-tuned somata. This relationship was absent in a novel environment, suggesting an experience dependent selective gating of dendritic spatial inputs. We then built a data-driven multicompartment computational model that could capture the experimentally observed correlations. Our model predicts that place cells exhibiting branch-specific tuning have more flexible place fields, while neurons with homogenous or co-tuned dendritic branches have higher place field stability. These findings demonstrate that spatial representation is organized in a branch-specific manner within dendrites of hippocampal pyramidal cells. Further, spatial inputs from dendrites to soma are selectively and dynamically gated in an experience-dependent manner, endowing both flexibility and stability to the cognitive map of space. One sentence summaryHippocampal pyramidal cells show branch-specific tuning for different place fields, and their coupling to their soma changes with experience of an environment.

neuroscience↗