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 (LEC GLU ) and GABAergic (LEC GABA ) projections are essential for object recognition memory. Silencing LEC GLU 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 LEC GLU also decreased place cell remapping between different environments validating this circuit drives pattern separation and context discrimination. Optogenetic circuit mapping confirmed that LEC GLU drives dominant feedforward inhibition to prevent CA3 somatic and dendritic spikes. However, conjunctively active LEC GABA suppresses this local inhibition to disinhibit CA3 pyramidal neuron soma and selectively boost integrative output of LEC and CA3 recurrent network. LEC GABA 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.

Sub-cellular population imaging tools reveal stable apical dendrites in hippocampal area CA3.

Anatomically segregated apical and basal dendrites of pyramidal neurons receive functionally distinct inputs, but it is unknown if this results in compartment-level functional diversity during behavior. Here we imaged calcium signals from apical dendrites, soma, and basal dendrites of pyramidal neurons in area CA3 of mouse hippocampus during head-fixed navigation. To examine dendritic population activity, we developed computational tools to identify dendritic regions of interest and extract accurate fluorescence traces. We identified robust spatial tuning in apical and basal dendrites, similar to soma, though basal dendrites had reduced activity rates and place field widths. Across days, apical dendrites were more stable than soma or basal dendrites, resulting in better decoding of the animal's position. These population-level dendritic differences may reflect functionally distinct input streams leading to different dendritic computations in CA3. These tools will facilitate future studies of signal transformations between cellular compartments and their relation to behavior.

Assessing Local and Branch-specific Activity in Dendrites.

Dendrites are elaborate neural processes which integrate inputs from various sources in space and time. While decades of work have suggested an independent role for dendrites in driving nonlinear computations for the cell, only recently have technological advances enabled us to capture the variety of activity in dendrites and their coupling dynamics with the soma. Under certain circumstances, activity generated in a given dendritic branch remains isolated, such that the soma or even sister dendrites are not privy to these localized signals. Such branch-specific activity could radically increase the capacity and flexibility of coding for the cell as a whole. Here, we discuss these forms of localized and branch-specific activity, their functional relevance in plasticity and behavior, and their supporting biophysical and circuit-level mechanisms. We conclude by showcasing electrical and optical approaches in hippocampal area CA3, using original experimental data to discuss experimental and analytical methodology and key considerations to take when investigating the functional relevance of independent dendritic activity.