# Cellular mechanisms of hippocampal theta oscillations

> **NIH NIH R21** · UNIVERSITY OF WASHINGTON · 2022 · $194,375

## Abstract

PROJECT SUMMARY/ABSTRACT
The mammalian brain has an incredible capacity to learn and store information that can be subsequently
retrieved. A key brain structure that supports cognition and the formation of new memories is the
hippocampus. Damage to the hippocampus impairs memory and results in debilitating maladies like
Alzheimer's disease or epilepsy. Studies in primates and rodents have provided a rich systems-level
understanding of hippocampal function and its interaction with other structures like neocortex. However,
models that explain hippocampus physiology at the cellular and microcircuit level exclusively come from
studies in rodents. Due in part to our limited understanding of the mechanisms that govern primate cellular
physiology, treatments for complex neurological diseases have fared poorly when introduced in human
clinical trials. Our long-range goal is to better understand how the primate hippocampus processes
information in support of memory at the cellular and microcircuit level, thus connecting cellular physiology
to network function in primates. Here we propose to develop a non-human primate model that allows the
study of the cellular and microcircuit physiology of the primate hippocampus. We will combine whole-cell
patch clamping and pharmacology in a novel in vitro approach to delineate the mechanisms that support
theta oscillations in monkeys. Theta oscillations reflect temporally coordinated network activity in the
hippocampus that occurs while attending to incoming stimuli and during successful memory encoding.
They are present in both rodents and primates, but this activity only sparsely occurs in primates,
suggesting that there are substantial differences in the neuronal circuits of the hippocampus and the
properties of its neurons across species. To understand how cellular physiology shapes the theta
oscillation in primates, we will both characterize the physiological properties of principal cells in the
monkey hippocampus and the effect that the critical theta neuromodulator acetylcholine has in regulating
the intrinsic properties of hippocampal neurons in vitro. The proposed experiments have the following
potential outcomes: 1) establish whether the cellular physiology of pyramidal neurons in the hippocampus
of monkeys differ from that of rodents, 2) identify mechanisms in monkeys at the cellular level that
contribute to coordinated network activity. These experiments will provide species-specific evidence for
a model that may translate better to human physiology.

## Key facts

- **NIH application ID:** 10371384
- **Project number:** 1R21MH126126-01A1
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Andres Barria
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $194,375
- **Award type:** 1
- **Project period:** 2022-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10371384

## Citation

> US National Institutes of Health, RePORTER application 10371384, Cellular mechanisms of hippocampal theta oscillations (1R21MH126126-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10371384. Licensed CC0.

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