# Connectivity and function of microcircuits in the superficial layers of the entorhinal cortex

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $398,787

## Abstract

Project Summary
Neuron loss and the reorganization of neural circuits in the superficial layers of entorhinal cortex are hallmarks
of Alzheimer’s disease and temporal lobe epilepsy, and memory impairments are among the troubling symptoms
of these diseases. Despite the knowledge that superficial entorhinal cell layers are selectively vulnerable in these
diseases, the local connectivity of entorhinal circuits, how different functional cell types within these layers
emerge, and how each cell type contributes to memory and spatial processing is only beginning to be revealed.
The entorhinal cortex has extensive recurrent connectivity between its layers, and harbors many functional cell
types such as grid cells, head-direction cells, border cells, context-selective cells, and other types of spatial and
nonspatial cells. However, this functional diversity neither maps directly onto particular cell layers nor onto
anatomically defined cell classes within layers. Each cell’s functional identity may therefore predominantly be
determined by local microcircuits. The objective of this proposal is to examine whether functional cell identities
in mEC, including grid cell firing and context-selective firing, emerge from circuit computations. We focus on
local connectivity within the superficial layers and hypothesize that layer II pyramidal cells selectively
contribute to rate coding in layer II stellate cells and that layer III inputs selectively contribute
to spatial coding, including grid firing, in layer II stellate cells. This hypothesis will be tested in two
specific aims. First, we will use viral tracing and patch clamp recordings with optical stimulation in entorhinal
slices to determine the connectivity of mEC layer II pyramidal cells and layer III pyramidal cells and, for
comparison, layer II stellate cells. Second, we will record from mEC cells in behaving mice while optogenetically
stimulating or inhibiting entorhinal cell populations. In two separate subaims, we will examine (1) the effects of
layer II pyramidal cell manipulations on the spatial and context-selective firing patterns of layer II stellate cells
and layer III pyramidal cells and (2) the effects of layer III pyramidal cell manipulations on spatial and context-
selective coding by layer II cells. Results from our aims will identify how local entorhinal circuits contribute to
the generation of specialized entorhinal cell types, including grid cells and context-selective cells. This will not
only fill gaps between theoretical models and experimental data, but also develop methods to selectively
manipulate different functional cell types in mEC. Our results will therefore advance our understanding of the
contribution of entorhinal cell types and cell layers to spatial and memory processing and thereby suggest
strategies for restoring entorhinal circuit function and ameliorating the progression of neurodegenerative
diseases.

## Key facts

- **NIH application ID:** 10159313
- **Project number:** 5R01NS097772-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Stefan Leutgeb
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $398,787
- **Award type:** 5
- **Project period:** 2017-09-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10159313

## Citation

> US National Institutes of Health, RePORTER application 10159313, Connectivity and function of microcircuits in the superficial layers of the entorhinal cortex (5R01NS097772-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10159313. Licensed CC0.

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