# Subiculm circuits for cortical feedback regulation of spatial mapping and learning

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2021 · $506,175

## Abstract

Project Summary / Abstract
 Encoding of environmental location and navigational behavior in mammals involves large ensembles of
specific neuron types across multiple interacting brain regions. “Place cell” and “grid cell” mapping of spatial
location in the CA1 region of hippocampus and medial entorhinal cortex (EC), respectively, is thought to be fed
forward to associative cortical brain regions including the posterior parietal cortex (PPC) and retrosplenial
cortex (RSP) to map conjunctions of egocentric and external spatial relationships. This notion implies that the
hippocampal-neocortical pathway involves a gradual transformation of spatial cognition to action along with
encoding of specific route information at intermediate processing stages. While the characterization of this
hippocampal feedforward output to the neocortical system has been conceptually useful for our understanding
of spatial navigation processes, it is now time to consider the role of the largely unexplored “top-down”
neocortical inputs from RSP to the hippocampus. The subiculum (SUB) is an under-investigated brain
structure well positioned to mediate circuit interactions between the hippocampal and neocortical systems.
Based on our recent discoveries, we hypothesize that specific subsets of SUB neurons receive significant
direct “top-down” inputs from RSP and that these inputs yield specialized SUB encoding of multiple spatial
relationships including the axis of travel, boundary vectors, and route sub-spaces. These SUB neurons are
expected to overlap with the population of CA1-projecting SUB neurons that exert direct feedback regulation of
hippocampus-associated spatial mapping and learning. We propose to study the synaptic circuit organization
and functional implications of this “top-down” pathway from RSP cortex, to SUB, to hippocampal CA1, using
recent technological advancements. To test the hypothesis, in Aim 1, we will map brain-wide circuit input
connections of CA1-projecting SUB neurons and compare these to EC-projecting, and RSP-projecting SUB
neurons using new viral tracing and optogenetic stimulation mapping. A combinatorial viral and genetic
strategy will be used to selectively label projection-specific SUB neurons for circuit studies and physiological
characterization. In Aims 2 and 3, we will link circuit connection mapping to neurophysiological function and
behavior. Tetrode recordings and in vivo GCaMP6-based calcium imaging of CA1 at single-cell resolution in
freely moving animals will resolve how RSP inputs and projection-specific SUB neurons modulate CA1 place
cell activities and how they contribute to spatial learning and navigation. The studies will be conducted in
conjunction with behavioral analyses addressing how animals learn object-place associations and routes
through environments having multiple interconnected pathways. Genetically targeted neuronal inactivation will
be used to establish the causality of circuit connections and function. The prop...

## Key facts

- **NIH application ID:** 10058286
- **Project number:** 5R01NS104897-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Douglas Arthur Nitz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $506,175
- **Award type:** 5
- **Project period:** 2017-12-15 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10058286

## Citation

> US National Institutes of Health, RePORTER application 10058286, Subiculm circuits for cortical feedback regulation of spatial mapping and learning (5R01NS104897-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10058286. Licensed CC0.

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