# Inhibitory hippocampal projections to the Supramammillary area

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2024 · $565,552

## Abstract

PROJECT SUMMARY
The supramammillary area (SuM) is increasingly appreciated for its role in a variety of functions, including
spatial and social novelty processing via its connections with the hippocampus. Specifically, the SuM has
projections to the CA2 and ventral dentate gyrus (DG), believed to be important for social processing, and to
the dorsal DG, believed to be important for spatial and contextual processing. The hippocampus provides
direct inhibitory input to the SuM, but the nature and function of this connectivity is completely unknown. The
studies outlined in the proposal would provide important basic science groundwork for understanding this
connectivity, with ultimate potential impacts for better understanding and treating a range of neurological
disorders, including but not limited to temporal lobe epilepsy. This includes examining the hippocampal
neurons providing the inhibitory input to the SuM, examining which subpopulations of SuM neurons receive
inhibitory hippocampal input, and the in vivo impact of manipulation of inhibitory hippocampal inputs to the
SuM. Based on our preliminary data, we predict that there are at least two populations of hippocampal
inhibitory neurons projecting to the SuM -- one expressing neuronal nitric oxide synthase (nNOS) and the other
expressing somatostatin – located in each region and along the entire anterior-posterior axis of the
hippocampus. We further predict the greatest number in the CA3 region. We predict, and our preliminary data
supports, that both SuM cells projecting to the ventral DG and SuM cells projecting to the dorsal DG receive
inhibitory hippocampal inputs. Importantly, we see the strongest connectivity so far from the ventral
hippocampus to SuM neurons projecting to the dorsal DG, arguing against a simple feedback inhibitory role of
this connection. To examine the function of inhibitory hippocampal inputs to the SuM in vivo, we will use
fiberphotometry to record from projection-defined SuM populations, during an assortment of behavioral tests,
while providing closed-loop optogenetic manipulation of inhibitory hippocampal inputs specifically at the time of
object or conspecific investigations. Collectively, the data will provide important insights into the nature of
hippocampal inhibitory inputs to the SuM, including the degree to which specific SuM populations are targeted,
and the functional significance of this connectivity, including as relates to social and spatial processing.

## Key facts

- **NIH application ID:** 10996324
- **Project number:** 1R01NS139469-01
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Esther Krook-Magnuson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $565,552
- **Award type:** 1
- **Project period:** 2024-07-01 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10996324

## Citation

> US National Institutes of Health, RePORTER application 10996324, Inhibitory hippocampal projections to the Supramammillary area (1R01NS139469-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10996324. Licensed CC0.

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