Biology subjects

Bakhurin, K. I.

Publications and source records attributed to Bakhurin, K. I..

3 recordsLinked to original sources

bioRxiv2025

Modular striatal dynamics and reciprocal inhibition orchestrate skilled action sequencing

The basal ganglia, particularly the striatum, are critical for orchestrating skilled behavioral sequences, yet the precise mechanisms underlying this process remain unclear. Using high-resolution kinematic tracking and neural recordings in mice performing a water-reaching task, we found spatially distributed modules of striatal projection neurons whose activity corresponded to the generation of each element in the sequence--aiming, reaching, and drinking. They are activated sequentially and exhibit reciprocal inhibition, ensuring a strict serial order. Optogenetic activation of the direct pathway of the orofacial module promoted licking while suppressing reaching. Reaching could in turn suppress stimulation-evoked licking, revealing bidirectional inhibitory interactions. Our findings demonstrate that the striatums modular organization, coupled with lateral inhibition, sculpts the temporal progression of actions, providing a mechanistic framework for understanding how the basal ganglia coordinate complex behaviors.

neuroscience↗

bioRxiv2023

Force tuning explains changes in phasic dopamine signaling during stimulus-reward learning

According to a popular hypothesis, phasic dopamine (DA) activity encodes a reward prediction error (RPE) necessary for reinforcement learning. However, recent work showed that DA neurons are necessary for performance rather than learning. One limitation of previous work on phasic DA signaling and RPE is the limited behavioral measures. Here, we measured subtle force exertion while recording and manipulating DA activity in the ventral tegmental area (VTA) during stimulus-reward learning. We found two major populations of DA neurons that increased firing before forward and backward force exertion. Force tuning is the same regardless of learning, reward predictability, or outcome valence. Changes in the pattern of force exertion can explain results traditionally used to support the RPE hypothesis, such as modulation by reward magnitude, probability, and unpredicted reward delivery or omission. Thus VTA DA neurons are not used to signal RPE but to regulate force exertion during motivated behavior.

neuroscience↗

bioRxiv2019

Opponent regulation of action performance and timing by striatonigral and striatopallidal pathways

The basal ganglia have been implicated in action selection and timing, but the relative contributions of the striatonigral (direct) and striatopallidal (indirect) pathways to these functions remain unclear. We investigated the effects of optogenetic stimulation of D1+ (direct) and A2A+ (indirect) neurons in the ventrolateral striatum in head-fixed mice on a fixed time reinforcement schedule. Direct pathway stimulation initiates licking, whereas indirect pathway stimulation suppresses licking and results in rebound licking after stimulation. Moreover, direct and indirect pathways also play distinct roles in timing. Direct pathway stimulation produced a resetting of the internal timing process, whereas indirect pathway stimulation transiently paused timing, and proportionally delayed the next bout of licking. Our results provide evidence for the continuous and opposing contributions of the direct and indirect pathways in the production and timing of reward-guided behavior.

neuroscience↗