Wu, A. K. | bioRxiv Science

bioRxiv2023

Dopamine lesions alter the striatal encoding of single-limb gait

The striatum an important role in motor control, and neurons in this area encode the bodys initiation, cessation, and speed of locomotion. However, it remains unclear whether the same neurons also encode the step-by-step rhythmic motor patterns of individual limbs that characterize gait. By combining high-speed video tracking, electrophysiology, and optogenetic tagging, we found that a sizable population of both D1 and D2 receptor expressing medium spiny projection neurons (MSNs) were phase-locked to the gait cycle of individual limbs in mice. Healthy animals showed balanced limb phase-locking between D1 and D2 MSNs, while dopamine depletion led to stronger phase-locking in D2 MSNs. These findings indicate that striatal neurons represent gait on a single-limb and step basis, and suggest that elevated limb phase-locking of D2 MSNs may underlie some of the gait impairments associated with dopamine loss.

neuroscience↗

bioRxiv2022

Physiological constraints on the rapid dopaminergic modulation of striatal reward activity

While the contribution of dopaminergic (DA) neurons to associative learning is firmly established, their importance for influencing imminent behavior on short (subsecond) timescales is less clear. Mechanistically, it is thought that DA neurons drive these behavioral changes because of their ability to rapidly alter striatal spiking activity. However, due to limitations of previous approaches, the straightforward prediction that striatal spiking is rapidly influenced by physiologically relevant DA signals has not been rigorously tested. Here, we monitored changes in spiking responses in the ventral striatum while transiently reducing or increasing DA levels. Contrary to the predicted effect, neither spontaneous nor reward-evoked striatal spiking activity was strongly influenced by optogenetic manipulations, except when DA exceeded reward-matched levels. These findings challenge the view that DA plays a major role in rapidly influencing striatal activity. Finally, they suggest a need to distinguish between the modulatory functions of DA under physiological and supra-physiological conditions.

neuroscience↗