# Cellular mechanisms in rodent prefrontal cortex

> **NIH NIH P20** · UNIVERSITY OF IOWA · 2021 · $111,790

## Abstract

Abstract
Parkinson’s disease (PD) causes deficits not only in motor function, but also in cognition and speech,
leading to significant loss of independence. Few interventions are available to treat these non-motor
symptoms, and current therapies can worsen them. Accumulating evidence suggests that dysfunction in
the prefrontal cortex (PFC) is responsible for impaired cognition and speech in PD. Our work shows that
patients with PD have impaired prefrontal 4 Hz rhythms, and these abnormal oscillations in local field
potentials correlate with impaired cognitive and speech processes. However, the pathophysiology that
leads to disruption of prefrontal rhythms in PD remains unclear.
The overall objective of the proposed research is to determine how PFC cortical circuits are destabilized
by pathophysiological processes in PD, using a combination of cell-type-specific tagging with in vivo two-
photon calcium imaging in awake behaving mice. Our hypothesis is that 4 Hz rhythms are orchestrated
by layer V neurons expressing D1-type dopamine receptors during interval timing. Both cognitive and
speech function require temporal organization of behavior that is vital to higher-level executive functions,
such as behavioral flexibility and planning. However, in patients with PD, temporal organization of
behavior is abnormal. Our team has modeled temporal deficits in PD using an elementary cognitive task
known as interval timing, during which a subject estimates a fixed interval of time. In PD patients, interval
timing is reliably disrupted. Interestingly, 4 Hz rhythms are nearly identical in humans and rodents, and
they are attenuated in both PD patients and rodent models of PD. The 4 Hz rhythms in the rodent medial
PFC (functionally analogous to the human mediofrontal cortex) coordinate cognitive control during
interval-timing tasks, but the cellular and laminar source of these rhythms is unknown.
In Aim 1 we will use in vivo 2-photon imaging in awake behaving mice to identify the cellular source of
prefrontal 4 Hz rhythms critical for interval timing tasks. In Aim 2 we will determine how PD-relevant
pathophysiology, including dopaminergic, cholinergic and alpha-synuclein affects prefrontal networks.
The expected outcomes of this research will be identifying the cells and circuits that give rise to
endogenous 4 Hz rhythms and determining the effects of specific PD pathological processes. These
insights will lead to a novel understanding of PFC function that could be relevant for understanding
cognitive and speech symptoms in human PD patients.

## Key facts

- **NIH application ID:** 10283243
- **Project number:** 1P20NS123151-01
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Georgina Aldridge
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $111,790
- **Award type:** 1
- **Project period:** 2021-09-17 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10283243

## Citation

> US National Institutes of Health, RePORTER application 10283243, Cellular mechanisms in rodent prefrontal cortex (1P20NS123151-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10283243. Licensed CC0.

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