Biology subjects

Zimmerman, C. A.

Publications and source records attributed to Zimmerman, C. A..

4 recordsLinked to original sources

bioRxiv2025

VTA dopamine neuron activity produces spatially organized value representations

What is the neural architecture by which dopamine (DA) determines choice? Reinforcement learning (RL) has suggested an algorithmic chain: prediction errors based on reward train predicted values for stimuli and actions, and thereby determine choice. Elements of this chain have been identified, but have yet to be convincingly assembled. Here we used optogenetic stimulation of putative prediction error neurons at the top of this chain - i.e., DA neurons in the ventral tegmental area (VTA) - and recorded the activity of thousands of neurons in their target structure - the striatum - in mice performing a task that dissociates VTA DA signalling, stimulus value, action value, and choice. Conventional RL models captured some features of the data, including DA-driven choice reinforcement and value correlates, but failed on two key observations: i) action and state value correlates were relatively weak in the VTAs main target, the nucleus accumbens (NAc), and ii) VTA DA could not reinforce actions in the absence of a reward-predictive cue (CS+). Instead, we find that VTA DA produces stimulus value representations in the NAc, which in turn generates action value representations downstream (e.g. the CP). We formalize these observations in a Conditioned Reinforcer model, where VTA DA specifically acts on stimuli rather than actions, and these stimulus value representations are used to drive choice reinforcement.

neuroscience↗

bioRxiv2025

Striatal pathways oppositely shift cortical activity along the decision axis

The cortex and basal ganglia are organized into multiple parallel loops that serve motor, limbic, and cognitive functions. The classic model of cortico-basal ganglia interactions posits that within each loop, the direct pathway of the basal ganglia activates the cortex and the indirect pathway inhibits it1-3. While this model has found support in the motor domain4,5, whether opponent control by the two pathways extends to the cognitive domain remains unknown. Here, we record from anterior cingulate cortex (ACC) and dorsomedial striatum (DMS) while inhibiting direct or indirect pathway neurons in DMS, as mice perform an accumulation-of-evidence task6-10. Inconsistent with the classic model, the manipulations do not produce opponent changes in overall ACC activity. Instead, the pathways exert opponent influence over a subpopulation of ACC neurons that encode accumulated sensory evidence, the task-relevant decision variable. The direction of the modulation depends on a neurons tuning to ipsilateral versus contralateral evidence, such that the two pathways generate opponent shifts in coding specifically along the decision axis. Thus, our results uncover unexpected specificity in the effects of basal ganglia pathways on the cortex, with the two pathways of the DMS exerting opponent control not on overall activity but on coding of the relevant task variable. This functional specificity may extend to other basal ganglia loops to support different aspects of adaptive behavior, with the pathways serving a general role in selecting and shifting cortical representations to subserve circuit-specific functions.

neuroscience↗

bioRxiv2023

A neural mechanism for learning from delayed postingestive feedback

Animals learn the value of foods based on their postingestive effects and thereby develop aversions to foods that are toxic1-6 and preferences to those that are nutritious7-14. However, it remains unclear how the brain is able to assign credit to flavors experienced during a meal with postingestive feedback signals that can arise after a substantial delay. Here, we reveal an unexpected role for postingestive reactivation of neural flavor representations in this temporal credit assignment process. To begin, we leverage the fact that mice learn to associate novel15-18, but not familiar, flavors with delayed gastric malaise signals to investigate how the brain represents flavors that support aversive postingestive learning. Surveying cellular resolution brainwide activation patterns reveals that a network of amygdala regions is unique in being preferentially activated by novel flavors across every stage of the learning process: the initial meal, delayed malaise, and memory retrieval. By combining high-density recordings in the amygdala with optogenetic stimulation of genetically defined hindbrain malaise cells, we find that postingestive malaise signals potently and specifically reactivate amygdalar novel flavor representations from a recent meal. The degree of malaise-driven reactivation of individual neurons predicts strengthening of flavor responses upon memory retrieval, leading to stabilization of the population-level representation of the recently consumed flavor. In contrast, meals without postingestive consequences degrade neural flavor representations as flavors become familiar and safe. Thus, our findings demonstrate that interoceptive reactivation of amygdalar flavor representations provides a neural mechanism to resolve the temporal credit assignment problem inherent to postingestive learning.

neuroscience↗

bioRxiv2022

A neural substrate of sex-dependent modulation of motivation by value

While there is emerging evidence of sex differences in decision-making behavior, the neural substrates that underlie such differences remain largely unknown. Here, we demonstrate that in mice performing a value-based decision-making task, while choices are similar between the sexes, motivation to engage in the task is modulated by action value in females more strongly than in males. Inhibition of activity in anterior cingulate cortex (ACC) neurons that project to the dorsomedial striatum (DMS) disrupts this relationship between value and motivation preferentially in females, without affecting choice in either sex. In line with these effects, in females compared to males, ACC-DMS neurons have stronger representations of negative outcomes, and more neurons are active when the value of the chosen option is low. In contrast, the representation of each choice is similar between the sexes. Thus, we identify a neural substrate that contributes to sex-specific modulation of motivation by value.

neuroscience↗