Prohofsky, J. | Search bioRxiv

bioRxiv2024

Superior colliculus projections drive dopamine neuron activity and movement but not value

To navigate dynamic environments, animals must rapidly integrate sensory information and respond appropriately to gather rewards and avoid threats. It is well established that dopamine (DA) neurons in the ventral tegmental area (VTA) and substantia nigra (SNc) are key for creating associations between environmental stimuli (i.e., cues) and the outcomes they predict. Critically, it remains unclear how sensory information is integrated into dopamine pathways. The superior colliculus (SC) receives direct visual input and is positioned as a relay for dopamine neuron augmentation. We characterized the anatomical organization and functional impact of SC projections to the VTA and SNc in rats. First, we show that neurons in the deep layers of SC synapse densely throughout the ventral midbrain, interfacing with projections to the striatum and ventral pallidum, and these SC projections excite dopamine and GABA neurons in the VTA/SNc in vivo. Despite this, cues predicting SC[->]VTA/SNc neuron activation did not reliably evoke behavior in an optogenetic Pavlovian conditioning paradigm, and activation of SC[->]VTA/SNc neurons did not support primary reinforcement or produce place preference/avoidance. Instead, we find that stimulation of SC[->]VTA/SNc neurons evokes head turning. Focusing optogenetic activation solely onto dopamine neurons that receive input from the SC was sufficient to invigorate turning, but not reinforcement. Turning intensity increased with repeated stimulations, suggesting that this circuit may underlie sensorimotor learning for exploration and attentional switching. Together our results show that collicular neurons contribute to cue-guided behaviors by controlling pose adjustments through interaction with dopamine neurons that preferentially engage movement instead of reward.

neuroscience↗

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↗