# A Control Theoretic Approach to Addressing Hippocampal Function

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2021 · $382,514

## Abstract

PROJECT SUMMARY
The hippocampal formation is critically involved in learning and memory. Neurodegenerative disorders such as
Alzheimer’s Disease dramatically impact this area, leading to severe and progressive memory loss. The
hippocampus appears to be the locus of an allocentric, cognitive map of the external world. This map is critical
not only for spatial cognition, but also for the conscious recollection of past experience. The hippocampus is
thought to bind the individual items and events of experience within a coherent spatiotemporal framework,
allowing the experience to be stored and retrieved as a conscious memory. Decades of investigation of
hippocampal place cells and the recent discovery of grid cells have revealed that this cognitive map arises from
the interaction of external sensory inputs with endogenously generated neural dynamics (underlying the
navigational strategy known as “path integration”). Classical neurophysiological studies with behaving animals
have amply characterized the powerful influence of environmental landmarks on the firing locations of these
spatial cells. Extending this approach to quantitatively investigate the internal processes of path integration has
proven technically challenging. Virtual reality technology, in combination with systems theory, offers opportunities
to solve these problems. We have designed and constructed a novel apparatus that allows us to manipulate the
visual inputs (both landmarks and optic flow) available to a rat navigating a real circular track as a function of its
movements, while preserving normal ambulatory and vestibular experience. Place cells recorded in this
apparatus replicate known standard phenomenology. In preliminary experiments, we induced a sustained,
increasing conflict between landmark information and path integration. Results demonstrate the capacity of the
system to recalibrate the path integrator when challenged with this sustained conflict. Further, we have developed
a novel approach for isolating the contribution of optic flow and other self-motion cues to the update of the neural
representation of position, free of the competing influence of landmarks. Specifically, we have developed an
online population decoder, and used the decoded output to control this cognitive representation during behavior
through real-time feedback manipulations of the optic flow. This approach will form the foundation of a novel
research program aimed at a comprehensive analysis of the external vs. internal determinants of the cognitive
map. Furthermore, this program promises to reveal important principles of neural computation relevant to general
problems of how the brain integrates external sensory input with internal, cognitive representations, ultimately
generating insights into the disordered thinking and hallucinations that are characteristic of schizophrenia and
other mental disorders.
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## Key facts

- **NIH application ID:** 10146494
- **Project number:** 5R01NS102537-05
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Noah John Cowan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $382,514
- **Award type:** 5
- **Project period:** 2017-08-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10146494

## Citation

> US National Institutes of Health, RePORTER application 10146494, A Control Theoretic Approach to Addressing Hippocampal Function (5R01NS102537-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10146494. Licensed CC0.

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