Biology subjects

Zimnik, A. J.

Publications and source records attributed to Zimnik, A. J..

4 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↗

bioRxiv2024

Identifying Interpretable Latent Factors with Sparse Component Analysis

In many neural populations, the computationally relevant signals are posited to be a set of latent factors - signals shared across many individual neurons. Understanding the relationship between neural activity and behavior requires the identification of factors that reflect distinct computational roles. Methods for identifying such factors typically require supervision, which can be suboptimal if one is unsure how (or whether) factors can be grouped into distinct, meaningful sets. Here, we introduce Sparse Component Analysis (SCA), an unsupervised method that identifies interpretable latent factors. SCA seeks factors that are sparse in time and occupy orthogonal dimensions. With these simple constraints, SCA facilitates surprisingly clear parcellations of neural activity across a range of behaviors. We applied SCA to motor cortex activity from reaching and cycling monkeys, single-trial imaging data from C. elegans, and activity from a multitask artificial network. SCA consistently identified sets of factors that were useful in describing network computations.

neuroscience↗

bioRxiv2020

Generation of Rapid Sequences by Motor Cortex

Rapid execution of motor sequences is believed to depend upon the fusing of movement elements into cohesive units that are executed holistically. We sought to determine the contribution of motor cortex activity to this ability. Two monkeys performed highly practiced two-reach sequences, interleaved with matched reaches performed alone or separated by a delay. We partitioned neural population activity into components pertaining to preparation, initiation, and execution. The hypothesis that movement elements fuse makes specific predictions regarding all three forms of activity. We observed none of these predicted effects. Instead, two-reach sequences involved the same set of neural events as individual reaches, but with a remarkable temporal compression: preparation for the second reach occurred as the first was in flight. Thus, at the level of motor cortex, skillfully executing a rapid sequence depends not on fusing elements, but on the ability to perform two computations at the same time.

neuroscience↗