Biology subjects

Kase, D.

Publications and source records attributed to Kase, D..

5 recordsLinked to original sources

bioRxiv2025

A comparison of movement-related neuronal activities in cerebellar- and basal ganglia-recipient regions of the macaque thalamus

The ventral lateral (VL) nucleus of the thalamus relays signals from the cerebellum (Cb) and basal ganglia (BG) to primary motor cortex (M1). In primates, glutamatergic Cb efferents from the deep cerebellar nuclei and GABAergic BG efferents from the internal segment of the globus pallidus (GPi) terminate in distinct subregions of VL: the posterior (VLp) and anterior (VLa) divisions, respectively. This anatomical segregation suggests that Cb- and BG-thalamocortical circuits may play distinct roles in motor control, which could be revealed by comparing movement-related activity in VLp and VLa. Here, we recorded single-unit activity from VLp and VLa, identified via electrical stimulation of superior cerebellar peduncle and GPi, during a choice reaction time reaching task. We also recorded from M1, which maintains bidirectional connections with both VLp and VLa. Peri-movement increases in firing began earlier in VLp than in VLa whereas decrease-type responses were more prevalent and prolonged in duration in VLa neurons as compared with VLp and M1. Time-resolved general linear model analysis showed dynamic encoding of task parameters, particularly movement direction, in all three regions. Direction encoding was strongest in M1, moderate in VLp, and weakest in VLa. Direction encoding in VLa also lagged behind that in M1 and VLp. Clustering analysis of direction encoding strength and timing revealed a subpopulation of VLp neurons that encoded direction particularly strongly during the reaction time period. These results highlight a limitation of traditional assumptions that activity characteristics are distributed homogeneously across neural populations and suggest a novel functional organization within VLp neurons.

neuroscience↗

bioRxiv2024

Movement-related activity in the internal globus pallidus of the parkinsonian macaque

Although the basal ganglia (BG) plays a central role in the motor symptoms of Parkinsons disease, few studies have investigated the influence of parkinsonism on movement-related activity in the BG. Here, we studied the perimovement activity of neurons in globus pallidus internus (GPi) of non-human primates during performance of a choice reaction time reaching task before and after the induction of parkinsonism by administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Neuronal responses, including increases or decreases in firing rate, were equally common in the parkinsonian brain as seen prior to MPTP and the distribution of different response types was largely unchanged. The slowing of behavioral reaction times and movement durations following the induction of parkinsonism was accompanied by a prolongation of the time interval between neuronal response onset and movement initiation. Neuronal responses were also reduced in magnitude and prolonged in duration after the induction of parkinsonism. Importantly, those two effects were more pronounced among decrease-type responses, and they persisted after controlling for MPTP-induced changes in the between-trial variability in response timing. Following MPTP the trial-to-trial timing of neuronal responses also became uncoupled from the time of movement onset and more variable in general. Overall, the effects of MPTP on temporal features of GPi responses were related to the severity of parkinsonian motor impairments whereas changes in response magnitude and duration did not reflect symptom severity consistently. These findings point to a previously underappreciated potential role for abnormalities in the timing of GPi task-related activity in the generation of parkinsonian motor signs. New & NoteworthyAlthough the globus pallidus internus (GPi) plays a central role in the cardinal symptoms of Parkinsons disease (PD), how parkinsonism alters the movement-related activity of GPi neurons remains understudied. Using a monkey model of PD, we found that: 1) the timing of GPi responses became uncoupled from movement onset. And 2) responses, especially decrease-type responses, became attenuated and prolonged. These abnormalities in GPi perimovement activity may contribute to the generation of parkinsonian motor signs.

neuroscience↗

bioRxiv2023

Detecting rhythmic spiking through the power spectra of point process model residuals

ObjectiveOscillations figure prominently as neurological disease hallmarks and neuromodulation targets. To detect oscillations in a neurons spiking, one might attempt to seek peaks in the spike trains power spectral density (PSD) which exceed a flat baseline. Yet for a non-oscillating neuron, the PSD is not flat: The recovery period ("RP", the post-spike drop in spike probability, starting with the refractory period) introduces global spectral distortion. An established "shuffling" procedure corrects for RP distortion by removing the spectral component explained by the inter-spike interval (ISI) distribution. However, this procedure sacrifices oscillation-related information present in the ISIs, and therefore in the PSD. We asked whether point process models (PPMs) might achieve more selective RP distortion removal, thereby enabling improved oscillation detection. ApproachIn a novel "residuals" method, we first estimate the RP duration (nr) from the ISI distribution. We then fit the spike train with a PPM that predicts spike likelihood based on the time elapsed since the most recent of any spikes falling within the preceding nr milliseconds. Finally, we compute the PSD of the models residuals. Main resultsWe compared the residuals and shuffling methods ability to enable accurate oscillation detection with flat baseline-assuming tests. Over synthetic data, the residuals method generally outperformed the shuffling method in classification of true-versus false-positive oscillatory power, principally due to enhanced sensitivity in sparse spike trains. In single-unit data from the internal globus pallidus (GPi) and ventrolateral anterior thalamus (VLa) of a parkinsonian monkey -- in which alpha-beta oscillations (8-30 Hz) were anticipated -- the residuals method reported the greatest incidence of significant alpha-beta power, with low firing rates predicting residuals-selective oscillation detection. SignificanceThese results encourage continued development of the residuals approach, to support more accurate oscillation detection. Improved identification of oscillations could promote improved disease models and therapeutic technologies.

neuroscience↗

bioRxiv2019

Weak modulation of thalamic discharge by basal ganglia output in association with a reaching task

Task-related activity in the ventral thalamus, a major target of basal ganglia output, is often assumed to be permitted or triggered by changes in basal ganglia activity through gating- or rebound-like mechanisms. To test those hypotheses, we sampled single-unit activity from connected basal ganglia output and thalamic nuclei (globus pallidus-internus, GPi, and ventrolateral-anterior nucleus, VLa) in monkeys performing a reaching task. Rate increases were the most common peri-movement change in both nuclei. Moreover, peri-movement changes generally began earlier in VLa than in GPi. Simultaneously-recorded GPi-VLa pairs rarely showed short-timescale spike-to-spike correlations or slow across-trials covariations and both were equally positive and negative. Finally, spontaneous GPi bursts and pauses were both followed by small, slow reductions in VLa rate. These results appear incompatible with standard gating and rebound models. Still, gating or rebound may be possible in other physiological situations: Simulations show how GPi-VLa communication can scale with GPi synchrony and GPi-to-VLa convergence, illuminating how synchrony of basal ganglia output during motor learning or in pathological conditions may render this pathway effective. Thus, in the healthy state, basal ganglia-thalamic communication during learned movement is more subtle than expected, with changes in firing rates possibly being dominated by a common external source.

neuroscience↗

bioRxiv2017

Dual Competition between the Basal Ganglia and the Cortex: from Action-Outcome to Stimulus-Response

Action-outcome (A-O) and stimulus-response (S-R) processes that are two forms of instrumental conditioning that are important components of decision making and action selection. The former adapts its response according to the outcome while the latter is insensitive to the outcome. An unsolved question is how these two processes emerge, cooperate and interact inside the brain in order to issue a unique behavioral answer. Here we propose a model of the interaction between the cortex, the basal ganglia and the thalamus based on a dual competition. We hypothesize that the striatum, the subthalamic nucleus, the internal pallidum (GPi), the thalamus, and the cortex are involved in closed feedback loops through the hyperdirect and direct pathways. These loops support a competition process that results in the ability for the basal ganglia to make a cognitive decision followed by a motor decision. Considering lateral cortical interactions (short range excitation, long range inhibition), another competition takes place inside the cortex allowing this latter to make a cognitive and a motor decision. We show how this dual competition endows the model with two regimes. One is oriented towards action-outcome and is driven by reinforcement learning, the other is oriented towards stimulus-response and is driven by Hebbian learning. The final decision is made according to a combination of these two mechanisms with a gradual transfer from the former to the latter. We confirmed these theoretical results on primates using a two-armed bandit task and a reversible bilateral inactivation of the internal part of the globus pallidus.

neuroscience↗