# Deciphering Neuronal Control of Behavioral Initiation and Suppression

> **NIH NIH DP5** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $417,500

## Abstract

PROJECT SUMMARY/ABSTRACT
Nearly one million people in the USA are living with Parkinson’s disease (PD). It is a disabling
neurodegenerative disease that causes progressive difficulty with movement, however equally
debilitating is the progressive impairment of motivation that is experienced by most patients.
Patients struggle to initiate things they want to do (apathy) and can also have difficulty
suppressing things that they do not want to do (impulsivity) – symptoms that are defined here as
impaired motivated behavior. There are no effective treatments for these symptoms and indeed,
some PD medications can make them worse. It is urgent to understand how these symptoms
originate in the brain in order develop new and effective treatments. The proposed research uses
precise optogenetic and physiological tools available in mice to characterize the brain networks
responsible for these symptoms of impaired motivation. These tools allow modulation and
monitoring of brain activity at millisecond timescales at the level of specific cell-types (neurons)
and groups of different neurons (circuits). This provides a powerful approach to determine how
specific neurons and circuits in the brain cause changes in behavior. We know that patients living
with PD have abnormal brain activity in an area deep in the brain known as the globus pallidus
(GPe). Therefore, this research proposes to use a high temporal resolution behavior task to
investigate the role of GPe in motivated behavior. In this task, normal mice quickly learn to lick a
water spout on hearing a cue that signals water is about to be delivered (Go cue), and restrain
licking after another cue signals that water is not forthcoming (NoGo cue). When the activity of
neurons in the GPe is increased, mice become more impulsive - specifically, they have difficulty
restraining themselves from licking the spout after the NoGo cue. This suggests that the GPe is
a key brain region involved in motivated behavior. However, it is not known which cells or circuits
in the GPe are responsible for driving this behavior, nor how they are disrupted in PD. The
proposed research will manipulate specific neural populations (Specific Aim 1) and neural circuits
(Specific Aim 2) in the GPe to determine how they contribute to motivated behavior in healthy
mice. These findings will be translated to a mouse model of PD (Specific Aim 3) to enable the
design of cell type- and circuit-specific interventions to rescue abnormal neural activity patterns
and behaviors seen in the PD model (Specific Aim 3). The long-term objective of this work is to
provide a framework to understand the neural circuit abnormalities underlying the diverse and
challenging symptoms experienced by patients with PD and other neuropsychiatric disorders, to
promote the development of more effective and specific pharmaceutical and surgical therapies.

## Key facts

- **NIH application ID:** 10933443
- **Project number:** 5DP5OD036140-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Emily Anne Ferenczi
- **Activity code:** DP5 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $417,500
- **Award type:** 5
- **Project period:** 2023-09-22 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10933443

## Citation

> US National Institutes of Health, RePORTER application 10933443, Deciphering Neuronal Control of Behavioral Initiation and Suppression (5DP5OD036140-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10933443. Licensed CC0.

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