Biology subjects

Wolff, A. R.

Publications and source records attributed to Wolff, A. R..

4 recordsLinked to original sources

bioRxiv2024

Valence ambiguity dynamically shapes striatal dopamine heterogeneity

Adaptive decision making relies on dynamic updating of learned associations where environmental cues come to predict positive and negatively valenced stimuli, such as food or threat. Flexible cue-guided behaviors depend on a network of brain systems, including dopamine signaling in the striatum, which is critical for learning and maintenance of conditioned behaviors. Critically, it remains unclear how dopamine signaling encodes multi-valent, dynamic learning contexts, where positive and negative associations must be rapidly disambiguated. To understand this, we employed a Pavlovian discrimination paradigm, where cues predicting positive and negative outcomes were intermingled during conditioning sessions, and their meaning was serially reversed across training. We found that rats readily distinguished these cues, and updated their behavior rapidly upon valence reversal. Using fiber photometry, we recorded dopamine signaling in three major striatal subregions -,the dorsolateral striatum (DLS), the nucleus accumbens core, and the nucleus accumbens medial shell - and found heterogeneous responses to positive and negative conditioned cues and their predicted outcomes. Valence ambiguity introduced by cue reversal reshaped striatal dopamine on different timelines: nucleus accumbens core and shell signals updated more readily than those in the DLS. Together, these results suggest that striatal dopamine flexibly encodes multi-valent learning contexts, and these signals are dynamically modulated by changing contingencies to resolve ambiguity about the meaning of environmental cues.

neuroscience↗

bioRxiv2023

Contexts facilitate dynamic value encoding in the mesolimbic dopamine system

Adaptive behavior in a dynamic environment often requires rapid revaluation of stimuli that deviates from well-learned associations. The divergence between stable value-encoding and appropriate behavioral output remains a critical test to theories of dopamines function in learning, motivation, and motor control. Yet how dopamine neurons are involved in the revaluation of cues when the world changes to alter our behavior remains unclear. Here we make use of pharmacology, in vivo electrophysiology, fiber photometry, and optogenetics to resolve the contributions of the mesolimbic dopamine system to the dynamic reorganization of reward-seeking. Male and female rats were trained to discriminate when a conditioned stimulus would be followed by sucrose reward by exploiting the prior, non-overlapping presentation of a separate discrete cue - an occasion setter. Only when the occasion setters presentation preceded the conditioned stimulus did the conditioned stimulus predict sucrose delivery. As a result, in this task we were able to dissociate the average value of the conditioned stimulus from its immediate expected value on a trial-to-trial basis. Both the activity of ventral tegmental area dopamine neurons and dopamine signaling in the nucleus accumbens were essential for rats to successfully update behavioral responding in response to the occasion setter. Moreover, dopamine release in the nucleus accumbens following the conditioned stimulus only occurred when the occasion setter indicated it would predict reward. Downstream of dopamine release, we found that single neurons in the nucleus accumbens dynamically tracked the value of the conditioned stimulus. Together these results reveal a novel mechanism within the mesolimbic dopamine system for the rapid revaluation of motivation.

neuroscience↗

bioRxiv2023

Sensory cues potentiate VTA dopamine mediated reinforcement

Sensory cues are critical for shaping decisions and invigorating actions during reward seeking. Dopamine neurons in the ventral tegmental area (VTA) are critical in this process, supporting associative learning in Pavlovian and instrumental settings. Studies of intracranial self stimulation (ICSS) behavior, which show that animals will work hard to receive stimulation of dopamine neurons, support the notion that dopamine transmits a reward or value signal to support learning. Recent studies have begun to question this, however, emphasizing dopamines value-free functions, leaving its contribution to behavioral reinforcement somewhat muddled. Here, we investigated the role of sensory stimuli in dopamine-mediated reinforcement, using an optogenetic ICSS paradigm in tyrosine hydroxylase (TH)-cre rats. We find that while VTA dopamine neuron activation in the absence of any external cueing stimulus is sufficient to maintain robust self stimulation, the presence of cues dramatically potentiates ICSS behavior. Our results support a framework where dopamine can have some base value as a reinforcer, but the impact of this signal is modulated heavily by the sensory learning context.

neuroscience↗

bioRxiv2023

VTA dopamine neurons drive spatiotemporally heterogeneous striatal dopamine signals during learning

Environmental cues, through Pavlovian learning, become conditioned stimuli that invigorate and guide animals toward acquisition of rewards. Dopamine neurons in the ventral tegmental area (VTA) and substantia nigra (SNC) are crucial for this process. Dopamine neurons are embedded in a reciprocally connected network with their striatal targets, the functional organization of which remains poorly understood. Here, we investigated how learning during optogenetic Pavlovian cue conditioning of VTA or SNC dopamine neurons directs cue-evoked behavior and shapes subregion-specific striatal dopamine dynamics. We used a fluorescent dopamine biosensor to monitor dopamine in the nucleus accumbens (NAc) core and shell, dorsomedial striatum (DMS), and dorsolateral striatum (DLS). We demonstrate spatially heterogeneous, learning-dependent dopamine changes across striatal regions. While VTA stimulation evoked robust dopamine release in NAc core, shell, and DMS, cues predictive of this activation preferentially recruited dopamine release in NAc core, starting early in training, and DMS, late in training. Corresponding negative prediction error signals, reflecting a violation in the expectation of dopamine neuron activation, only emerged in the NAc core and DMS, and not the shell. Despite development of vigorous movement late in training, conditioned dopamine signals did not similarly emerge in the DLS, even during Pavlovian conditioning with SNC dopamine neuron activation, which elicited robust DLS dopamine release. Together, our studies show broad dissociation in the fundamental prediction and reward-related information generated by different dopamine neuron populations and signaled by dopamine across the striatum. Further, they offer new insight into how larger-scale plasticity across the striatal network emerges during Pavlovian learning to coordinate behavior.

neuroscience↗