Browsing by Author "Kim, Namsoo"

The striatum is the input nucleus of basal ganglia, a group of subcortical nuclei that includes the striatum, globus pallidus, subthalamic nucleus, and substantia nigra. These brain regions have been implicated in control and coordination of motor planning and action selection. Especially, the dorsal striatum (sensorimotor striatum) is important for movement control. Movement is a change in body configuration or posture. A key feature of voluntary movements is that we can arbitrarily vary movement velocity, defined as the rate of change in body configurations. Despite extensive studies that have attempted to elucidate the relationship between neurons in the dorsal striatum and movement, the mechanism of how striatal activity in the dorsal striatum contributes to movement velocity remains unclear. One reason is that traditional experimental designs of the basal ganglia have either considered actions as discrete events or neglected to measure movements with the precise spatial and temporal resolutions required to understand the neural substrates of behavior. For example, many studies have used movement initiation as a behavioral variable, but it is unclear how fast the animal moved, in what direction, or what effectors were used. The following experiments were designed to investigate the role of striatal neurons in controlling movement velocity in mice. The first set of experiments (Chapter 2) examined the relationship between striatal activity and movement velocity. Using wireless in vivo electrophysiology recording and video tracking, we recorded single‐unit activity from spiny projection neurons (SPNs) and fast‐spiking interneurons (FSIs) while monitoring the movements of mice. In Experiment 1, we trained animals to generate movements toward the waterspout by water‐depriving them and giving them periodic cued sucrose rewards. We found high correlations between neural activity and direction-specific movement velocity. This correlation was found in both putative SPNs and FSIs. In Experiment 2, to rule out the possibility that the observed correlations were due to reward expectancy, we repeated the same procedure but added a condition in which sucrose delivery was replaced by an aversive air puff stimulus. The air puff generated avoidance movements that were clearly different from movements on rewarded trials. However, the same neurons that showed velocity correlation on reward trials exhibited a similar correlation on air puff trials. These experiments show that the firing rate of striatal neurons reflects direction-specific movement velocity regardless of the valence of the outcome. The second set of experiments (Chapter 3) examined a striatal microcircuit underlying pursuing behavior. The SPNs and FSIs in the striatum compose a striatal microcircuit that provides a feedforward inhibition circuit in which glutamatergic inputs excite the FSIs that then inhibit the SPNs. By using 3D motion capture, in vivo electrophysiology and calcium imaging, we recorded neural activity from SPNs and FSIs while precisely monitoring mice during a task where they are trained to follow a moving target to earn a reward. We showed that, in the sensorimotor striatum, parvalbumin-positive (PV+) FSIs can represent the distance between self and target during pursuit behavior, while SPNs can represent movement velocity. We found that PV+ FSIs were shown to regulate velocity-related SPNs during pursuit, so that movement velocity is continuously regulated by distance to target. Moreover, bidirectional manipulation of PV+ FSIs can selectively disrupt pursuit behavior by increasing or decreasing the distance. These experiments reveal a key role of the microcircuit between FSIs and SPNs in pursuit behavior and elucidate how this circuit implements the distance to velocity transformation by formalizing the explicit computation used. The third set of experiments (Chapter 4) examined the role of direct and indirect pathways in velocity control during switching behavior in which animals were trained on a task with two different targets. Mice had to approach one target, then switch to another target to earn a reward. Direct pathway (striatonigral) neurons express D1 receptors and project to the substantia nigra pars reticulata (SNr) and other BG output nuclei. Indirect pathway (striatopallidal) neurons express D2 and A2A receptors and project primarily to the globus pallidus. Using 3D motion capture and in vivo calcium imaging, we recorded neural activity from direct and indirect pathway SPNs while monitoring mice’s behavior as they switched between the two targets. We showed that the direct pathway is responsible for increase of velocity whereas the indirect pathway is involved in decrease of velocity. Moreover, bidirectional manipulation of direct and indirect pathways can increase and decrease the movement velocity causing bidirectional errors. These experiments reveal the opposite role in velocity control between direct and indirect pathways during switching behavior and elucidate how these pathways contribute to control of movement velocity. Taken together, these experiments demonstrate that not only is the striatum involved in the control of movements, they provide the mechanism of how striatal microcircuits in the dorsal striatum contributes to movement velocity.