Summary: The brain is continuously classifying incoming information as positive or negative to guide approach or avoidance behaviors that support survival. New research shows that two major neuron types in the nucleus accumbens—the D1 and D2 medium spiny neurons—are both engaged by rewarding and aversive events but play different roles during learning and when associations change.
Using real-time calcium imaging in mice, the research team found that D2 neurons are particularly important for updating learned associations, for example when a stimulus that once signaled danger no longer does. These findings shed light on why people with anxiety disorders or post-traumatic stress disorder may have trouble letting go of negative memories and could point toward more targeted interventions.
Key Facts:
- D1 and D2 neurons: Both neuron classes in the nucleus accumbens respond to both rewarding and aversive stimuli, yet they contribute differently to learning.
- D2 neurons and extinction: D2-medium spiny neurons are essential for extinguishing aversive associations when contingencies change.
- Mental health relevance: A clearer understanding of D2 function may help guide new approaches for treating anxiety and PTSD, where maladaptive negative associations persist.
Source: BIAL Foundation
The human brain contains billions of neurons that constantly receive information from the outside world. To act effectively, neural circuits must evaluate each stimulus and determine whether it is positive or negative; positive cues typically promote approach behavior, while negative cues trigger avoidance responses that enhance survival.
The nucleus accumbens (NAc) is a central hub involved in evaluating and encoding stimulus valence, yet how its two principal neuron populations—D1- and D2-expressing medium spiny neurons (MSNs)—represent appetitive versus aversive events and guide learning has been unclear.
To explore these circuit dynamics, researchers led by Ana João Rodrigues and Carina Soares-Cunha at ICVS, University of Minho, with support from the BIAL Foundation, examined how D1- and D2-MSNs in the NAc shell respond during exposure to both rewarding and aversive stimuli and during associative learning.
By tracking activity in hundreds of individual neurons while mice experienced stimuli of opposing valence, the team showed that both D1- and D2-MSN populations are co-recruited during learning: they respond together to appetitive and aversive events, but the patterns and dynamics of their responses differ.
Published in Nature Communications under the title Dynamic representation of appetitive and aversive stimuli in nucleus accumbens shell D1- and D2-medium spiny neurons, the study used advanced microendoscopic calcium imaging to monitor neural activity in behaving animals. The results reveal that although individual neurons can shift their coding over time, population activity from either D1 or D2 MSNs can discriminate unconditioned stimuli of opposite valence. However, predictive cues that signal those outcomes were not discriminated as reliably by individual populations.
Crucially, when stimulus–outcome contingencies were altered—such as when a formerly aversive cue no longer predicted an unpleasant outcome—the neural response in the NAc changed asymmetrically. D2-MSNs showed more pronounced changes in activity, and optogenetic experiments demonstrated that disrupting D2-MSN activity interfered with the extinction of aversive associations. This provides causal evidence that D2 neurons are necessary for updating and diminishing learned negative responses.
“Difficulty in modifying negative associations is a hallmark of anxiety and post-traumatic stress,” notes Carina Soares-Cunha. “A deeper understanding of how D2 neurons contribute to extinction processes could inform the development of targeted treatments.”
The study emphasizes that an identical external stimulus can evoke very different reactions depending on context and personal history. For example, fireworks may signal celebration and joy for many people, while in a former combatant they can provoke acute anxiety by recalling traumatic memories, even in a safe environment. The brain’s ability to reclassify external cues based on prior experience—and to adapt when those associations change—depends on complex, flexible neuronal circuits such as those described in this work.
This research was conducted in collaboration with Rui Costa and Gabriela Martins from Columbia University and the Allen Institute in the United States.
Funding: In addition to support from the BIAL Foundation, the research received co-funding from the European Research Council, the la Caixa Foundation, and the Foundation for Science and Technology.
About this neuroscience research news
Author: Sandra Pinto
Source: BIAL Foundation
Contact: Sandra Pinto – BIAL Foundation
Image: The image is credited to Neuroscience News
Original Research: Open access. “Dynamic representation of appetitive and aversive stimuli in nucleus accumbens shell D1- and D2-medium spiny neurons” by Carina Soares-Cunha et al., published in Nature Communications.
Abstract
Dynamic representation of appetitive and aversive stimuli in nucleus accumbens shell D1- and D2-medium spiny neurons
The nucleus accumbens (NAc) is a central brain region for motivated behaviors, but how distinct neuronal populations encode appetitive versus aversive stimuli has remained unclear.
Using microendoscopic calcium imaging in mice, the authors tracked activity in NAc shell D1- and D2-medium spiny neurons during exposure to stimuli of opposing valence and throughout associative learning.
Despite individual neurons changing their coding over time, population-level activity from both D1- and D2-MSNs could reliably distinguish unconditioned stimuli of opposite valence, while predictive cues were less distinctly represented by each population alone.
Both D1- and D2-MSNs were co-recruited during appetitive and aversive conditioning, indicating concurrent involvement in associative learning. When stimulus–outcome contingencies were reversed or extinguished, D2-MSNs exhibited larger shifts in activity. Optogenetic manipulation of D2-MSNs provided causal evidence that this population is necessary for the extinction of aversive associations.
These findings detail how NAc shell neurons represent valence, Pavlovian associations, and their extinction, offering insight into the neural mechanisms that shape motivated behavior.