Biology subjects

Bakhurin, K.

Publications and source records attributed to Bakhurin, K..

7 recordsLinked to original sources

bioRxiv2026

A dual-color miniature endoscope for calcium imaging in behaving mice

Calcium imaging with miniature endoscopes has become an essential tool in neuroscience, but conventional miniscopes typically record signals from only a single calcium indicator. Here, we present a dual-color miniature endoscope (miniscope) that enables simultaneous calcium imaging from two neuronal populations using spectrally distinct genetically encoded indicators. In freely moving mice, we used this system to record activity from striatal neurons of the direct (dSPN) and indirect (iSPN) pathways. We showed that dSPNs were activated earlier than iSPNs during contraversive movements, with dSPNs preferentially active during acceleration and iSPNs during deceleration. During ipsiversive turns, however, this temporal relationship was reversed. These findings indicate that dSPNs and iSPNs are not concurrently active, but instead exhibit complementary, direction-dependent dynamics that govern movement velocity. Our dual-color miniscope provides a compact, cost-effective platform for simultaneous two-population imaging, offering new opportunities to dissect coordinated activity across neural circuits in freely behaving animals.

neuroscience↗

bioRxiv2025

Elucidating an anterior cingulate circuit for self-initiated actions and rescue of Parkinsonian akinesia

Dopamine (DA) depletion is known to result in Parkinsonian symptoms such as the inability to initiate movements (akinesia). While Parkinsonian akinesia is traditionally associated with reduced DA signaling in the striatum, the contribution of cortical regions that also receive DA projections and project to the striatum remains unclear. Here, we identify a previously unexplored cortical circuit involving D1-like dopamine receptor-expressing neurons in the anterior cingulate cortex (ACC) that is critical for initiating goal-directed movements. We find that a selective activation of ACC-D1+ neurons can flexibly drive targeted movement and locomotion even in akinetic mice after dopamine depletion or receptor antagonism. These findings uncover a cortical mechanism for movement initiation and offer promising new therapeutic targets for treating Parkinsonian akinesia.

neuroscience↗

bioRxiv2024

GABAergic neurons from the ventral tegmental area represent and regulate force vectors

The ventral tegmental area (VTA), a midbrain region associated with motivated behaviors, consists predominantly of dopaminergic (DA) neurons and GABAergic (GABA) neurons. Previous work has suggested that VTA GABA neurons provide a reward prediction, which is used in computing a reward prediction error. In this study, using in vivo electrophysiology and continuous quantification of force exertion in head-fixed mice, we discovered distinct populations of VTA GABA neurons that exhibited precise force tuning independently of learning, reward prediction, and outcome valence. Their activity usually preceded force exertion, and selective optogenetic manipulations of these neurons systematically modulated force exertion without influencing reward prediction. Together, these findings show that VTA GABA neurons continuously regulate force vectors during motivated behavior.

neuroscience↗

bioRxiv2023

Attenuating midline thalamus bursting to mitigate absence epilepsy

Advancing the mechanistic understanding of absence epilepsy is crucial for developing new therapeutics, especially for patients unresponsive to current treatments. Utilizing a recently developed mouse model of absence epilepsy carrying the BK gain-of-function channelopathy D434G, here we report that attenuating the burst firing of midline thalamus (MLT) neurons effectively prevents absence seizures. We found that enhanced BK channel activity in the BK-D434G MLT neurons promotes synchronized bursting during the ictal phase of absence seizures. Modulating MLT neurons through pharmacological reagents, optogenetic stimulation, or deep brain stimulation effectively attenuates burst firing, leading to reduced absence seizure frequency and increased vigilance. Additionally, enhancing vigilance by amphetamine, a stimulant medication, or physical perturbation also effectively suppresses MLT bursting and prevents absence seizures. These findings suggest that the MLT is a promising target for clinical interventions. Our diverse approaches offer valuable insights for developing new therapeutics to treat absence epilepsy. HighlightsThe midline thalamus (MLT) is a key thalamic region for absence seizure pathogenesis MLT neurons exhibit synchronized bursting during ictal phase. BK channel contributes to MLT burst firing Attenuating MLT bursting increases vigilance and suppresses absence seizures

neuroscience↗

bioRxiv2020

Ventral tegmental dopamine neurons control the impulse vector during motivated behavior

The Ventral Tegmental Area (VTA) is a major source of dopamine, especially to the limbic brain regions. Despite decades of research, the function of VTA dopamine neurons remains controversial. Here, using a novel head-fixed behavioral system with five orthogonal force sensors, we show for the first time that distinct populations of VTA dopamine activity precisely represent the impulse vector (force exerted over time) generated by the animal. Optogenetic excitation of VTA dopamine neurons quantitatively determines impulse in the forward direction, and optogenetic inhibition produces impulse in the backward direction. At the same time, these neurons also regulate the initiation and execution of anticipatory licking. Our results indicate that VTA controls the magnitude, direction, and duration of force used to move towards or away from any motivationally relevant stimuli. One Sentence SummaryVTA dopamine bidirectionally controls impulse vector and anticipatory behavior

neuroscience↗

bioRxiv2019

A head-fixation system for continuous monitoring of force generated during behavior

Many studies in neuroscience use head-fixed behavioral preparations, which confer a number of advantages, including the ability to limit the behavioral repertoire and use techniques for large-scale monitoring of neural activity. But traditional studies using this approach use extremely limited behavioral measures, in part because it is difficult to detect the subtle movements and postural adjustments that animals naturally exhibit during head fixation. Here we report a new head-fixed setup with analog load cells capable of precisely monitoring the continuous forces exerted by mice. The load cells reveal the dynamic nature of movements generated not only around the time of task-relevant events, such as presentation of stimuli and rewards, but also during periods in between these events, when there is no apparent overt behavior. It generates a new and rich set of behavioral measures that have been neglected in previous experiments. We detail the construction of the system, which can be 3D-printed and assembled at low cost, show behavioral results collected from head-fixed mice, and demonstrate that neural activity can be highly correlated with the subtle, whole-body movements continuously produced during head restraint.

neuroscience↗

bioRxiv2019

Precise Coordination of 3-dimensional Rotational Kinematics by Ventral Tegmental Area GABAergic Neurons

The Ventral Tegmental Area (VTA) is a midbrain region implicated in a variety of motivated behaviors. However, the function of VTA GABAergic (Vgat+) neurons remains poorly understood. Here, using 3D motion capture, in vivo electrophysiology and calcium imaging, and optogenetics, we demonstrate a novel function of VTAVgat+ neurons. We found three distinct populations of neurons, each representing head angle about a principal axis of rotation: pitch, roll, and yaw. For each axis, opponent cell groups were found that increase firing when the head moves in one direction, and decrease firing in the opposite direction. Selective excitation and inhibition of VTAVgat+ neurons generate opposite rotational movements. The relationship between these neurons and head angle is degraded only at the time of reward consumption, at which point all head-angle related neuronal subpopulations show indistinguishable reward-related responses. Thus, VTAVgat+ neurons serve a critical role in the control of rotational kinematics while pursuing a moving target. This general-purpose steering function can guide animals toward desired spatial targets in any motivated behavior.

neuroscience↗