The Muñoz Lab

The Laboratory of Braulio Muñoz, PhD, within the Department of Biochemistry, Molecular Biology and Pharmacology at Indiana University School of Medicine, investigates the neurocircuitry of behaviors associated with motivation and habit learning, with a special interest in the role and function of inhibitory transmission (GABA and glycine). The Muñoz Lab uses mouse models of addiction and neurodegenerative diseases (e.g., Parkinson's Disease), basic biochemical analyses (gene and protein expression assessments), electrophysiological measures on brain tissue, neurocircuitry dissection (optogenetics and chemogenetics), microscopy, and mouse behavioral assessments. The Muñoz Lab also employs various adeno-associated viral vector treatments to manipulate the function of brain cells and to measure their function in physiological and behavioral assays, ultimately aiming to understand how neurocircuitries are affected by or regulate disease states.

Active Research

*

Active Research *

Alcohol Use Disorders

The Impact of Alcohol on Inhibitory Corticostriatal Transmission

Alcohol Use Disorders (AUDs) affect millions of people in the United States, imposing a profound socioeconomic burden. A hallmark of AUDs and other addictive diseases is a shift from goal-directed to habitual, compulsive drug use. The striatum, along with its inputs from different brain regions like the cortex, thalamus, and amygdala, plays a critical role in this transition from goal-directed to habitual behaviors, including those related to drug use. Therefore, it is crucial to understand how alcohol and other drugs of abuse alter the striatal neural circuitry that governs this transition. Furthermore, exploring the neural mechanisms by which the striatum and its inputs determine goal-directed and habitual drug use is essential.

This project assesses the impact of alcohol on inhibitory neural transmission within these brain regions, with special focus on the AIC-DLS circuit. We also investigate how manipulations of this neural circuitry alter alcohol consumption and related behaviors such as reward perception, anxiety, locomotor responses, and motivation. We hope that a deeper understanding of the interactions between alcohol and striatal inhibitory neurocircuits will reveal novel and more effective therapeutic strategies for treating AUDs.

Parkinson’s Disease

The Impact of Dopamine Lesions on Glycine Receptors in Mediating Parkinson's Disease Progression

Parkinson's disease (PD) affects millions of people worldwide. Interestingly, both Alcohol Use Disorders (AUDs) and PD impact the basal ganglia, a brain region critical for regulating striatal reward and motor circuits. Currently, there is no treatment available to delay or stop the progression of PD. However, the most effective treatment to alleviate motor symptoms is the use of Levodopa, but prolonged use leads to dyskinesia and episodic psychosis events. Recent studies have shown that the progression of these symptoms can be treated using glycine transporter type 1(GlyT1) inhibitors such as bitopertin, which activate NMDA and glycine receptors (GlyRs). Interestingly, using GlyT1 inhibitor in the striatum (the nucleus of the basal ganglia), increases glycine concentration leading to the activation of striatal GlyRs, increasing dopamine release and promoting neuroprotection.

While the role of GlyRs in the lasting impact of PD progression, particularly concerning motor-related behaviors later in life and on physiology, has received limited study, these receptors represent a compelling pharmacological target for treating PD.

The primary goal of this project is to determine the neuroprotective role of glycine receptors in mitigating or delaying PD progression.