Human Substantia Nigra Neurons Encode Reward Expectations.

Dopamine (DA) signals originating from substantia nigra (SN) neurons are centrally involved in the regulation of motor and reward processing. DA signals behaviorally relevant events where reward outcomes differ from expectations (reward prediction errors, RPEs). RPEs play a crucial role in learning optimal courses of action and in determining response vigor when an agent expects rewards. Nevertheless, how reward expectations, crucial for RPE calculations, are conveyed to and represented in the dopaminergic system is not fully understood, especially in the human brain where the activity of DA neurons is difficult to study. One possibility, suggested by evidence from animal models, is that DA neurons explicitly encode reward expectations. Alternatively, they may receive RPE information directly from upstream brain regions. To address whether SN neuron activity directly reflects reward expectation information, we directly examined the encoding of reward expectation signals in human putative DA neurons by performing single-unit recordings from the SN of patients undergoing neurosurgery. Patients played a two-armed bandit decision-making task in which they attempted to maximize reward. We show that neuronal firing rates (FR) of putative DA neurons during the reward expectation period explicitly encode reward expectations. First, activity in these neurons was modulated by previous trial outcomes, such that FR were greater after positive outcomes than after neutral or negative outcome trials. Second, this increase in FR was associated with shorter reaction times, consistent with an invigorating effect of DA neuron activity during expectation. These results suggest that human DA neurons explicitly encode reward expectations, providing a neurophysiological substrate for a signal critical for reward learning.

Multimodal sensory control of motor performance by glycinergic interneurons of the mouse spinal cord deep dorsal horn.

Sensory feedback is integral for contextually appropriate motor output, yet the neural circuits responsible remain elusive. Here, we pinpoint the medial deep dorsal horn of the mouse spinal cord as a convergence point for proprioceptive and cutaneous input. Within this region, we identify a population of tonically active glycinergic inhibitory neurons expressing parvalbumin. Using anatomy and electrophysiology, we demonstrate that deep dorsal horn parvalbumin-expressing interneuron (dPV) activity is shaped by convergent proprioceptive, cutaneous, and descending input. Selectively targeting spinal dPVs, we reveal their widespread ipsilateral inhibition onto pre-motor and motor networks and demonstrate their role in gating sensory-evoked muscle activity using electromyography (EMG) recordings. dPV ablation altered limb kinematics and step-cycle timing during treadmill locomotion and reduced the transitions between sub-movements during spontaneous behavior. These findings reveal a circuit basis by which sensory convergence onto dorsal horn inhibitory neurons modulates motor output to facilitate smooth movement and context-appropriate transitions.