Biology subjects

Collins, V. L.

Publications and source records attributed to Collins, V. L..

3 recordsLinked to original sources

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

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↗

bioRxiv2022

Cholinergic Interneurons Drive Motivation by Promoting Dopamine Release in the Nucleus Accumbens

Motivation to work for potential rewards is critically dependent on dopamine (DA) in the nucleus accumbens (NAc). DA release from NAc axons can be controlled by at least two distinct mechanisms: 1) action potentials propagating from DA cell bodies in the ventral tegmental area (VTA), and 2) activation of {beta}2* nicotinic receptors by local cholinergic interneurons (CINs). How CIN activity contributes to NAc DA dynamics in behaving animals remains unclear. We monitored DA release in the NAc Core of awake, unrestrained rats while simultaneously monitoring or manipulating CIN activity at the same location. CIN stimulation rapidly evoked DA release, and in contrast to slice preparations, this DA release showed no indication of short-term depression or receptor desensitization. The sound of food delivery evoked a brief joint increase in CIN population activity and DA release, with a second joint increase as rats approached the food. In an operant task, we observed fast ramps in CIN activity during approach behaviors, either to start the trial or to collect rewards. These CIN ramps co-occurred with DA release ramps, without corresponding changes in the firing of VTA DA neurons. Finally, we examined the effects of blocking CIN influence over DA release through local NAc infusion of DH{beta}E, a selective antagonist of [Formula] nicotinic receptors. DH{beta}E dose-dependently interfered with motivated approach decisions, mimicking the effects of a DA antagonist. Our results support a key influence of CINs over motivated behavior via the local regulation of DA release.

neuroscience↗