Neuronal substrates governing approach/avoidance conflict

The National Institute of Mental Health awarded the University of Puerto Rico Medical Sciences Campus $706,471 on August 5, 2026, under the Mental Health Research Grants program (CFDA 93.242) to characterize the neuronal substrates governing approach and avoidance conflict behavior in mice.

The recipient will conduct three research aims using fiber photometry, virally-mediated cellular signal ablation, and optogenetics in mice trained in platform-mediated avoidance tasks. Aim 1 characterizes how nucleus accumbens neurons and astrocytes encode approach and avoidance conflict learning and expression via calcium fiber photometry. Aim 2 ablates signaling of nucleus accumbens neurons and astrocytes to probe their role in approach and avoidance conflict learning. Aim 3 uses optogenetic silencing of nucleus accumbens neurons and astrocytes to probe their role in conflict expression. The research addresses a knowledge gap in understanding how opposing motivational circuits interact during conflict, with implications for anxiety, depression, and addiction.

The award is a Project Grant, assistance type standard for NIMH research support. The period of performance runs through April 30, 2031. Work is performed in Puerto Rico. The University of Puerto Rico serves as the parent organization; the Medical Sciences Campus is the immediate recipient.

Abstract

Many research groups concentrate on elucidating the substrates underlying reward approach or avoidance behaviors, resulting in a wealth of datasets detailing neuronal circuits governing motivation. However, the dynamics of opposing motivational circuits operating during approach/avoidance conflicts remain poorly understood. This knowledge GAP is significant, as compromised approach/avoidance behaviors are hallmark features of anxiety, depression, and addiction. The nucleus accumbens (NAC) is a key mediator of approach/avoidance conflict. Here, we propose to characterize the role of NAC neurons and astrocytes and circuits in influencing approach/avoidance conflict behaviors in mice, using fiber photometry, virally-mediated cellular signal ablation, and optogenetics in mice trained in the platform-mediated avoidance task. In aim 1, we will characterize how NAC neurons and astrocytes encode approach/avoidance conflict learning and expression with calcium fiber photometry in mice training in the platform-mediated avoidance task. In aim 2, we will ablate signaling of NAC neurons and astrocytes to probe their role in approach/avoidance conflict learning in mice training in the platform-mediated avoidance task the activity of NAC cell types and circuits during behavioral conflict in platform-mediated avoidance. In aim 3, we will optogenetically silence NAC neurons and astrocytes to probe their role in approach/avoidance conflict expression in mice training in the platform-mediated avoidance task. Findings from this work will shed light on how NAC mediates approach/avoidance conflict and potentially shed light into the role of NAC in psychiatric disorders involving poor approach/avoidance behaviors.