Biology subjects

Aristieta, A.

Publications and source records attributed to Aristieta, A..

4 recordsLinked to original sources

bioRxiv2026

L-DOPA Rescues Reach Height but Not Trajectory Area in a Bimanual String-Pulling Behavior in Parkinsonian Rats

While gross motor changes in Parkinson's disease, bradykinesia, hypokinesia, difficulty initiating movement, have been well studied in rodent models of the disease, limb movements, and especially bimanual coordination deficits, are more difficult to study in these animal models. Here we describe a novel bimanual string-pulling task that can be used to generate a rich repertoire of behaviors that require limb and bimanual coordination in rats with unilateral 6-hydroxydopamine (6-OHDA) lesion. We show that 6-OHDA lesion significantly reduces string speed, pulling bout duration, paw speed especially during reaching, and reduces the area of paw trajectories during pulling. However, it does not affect the variability around that movement trajectory. We also show that levodopa (L-DOPA) treatment restores many of these measures but not all. L-DOPA restores paw speed and string-pulling speed and fully restores paw reach height and pulling bout duration, but has no effect on trajectory area. Together, our results demonstrate that dopamine depletion differentially effects features of this bimanual coordination task, that L-DOPA mostly, but not fully, restores string pulling performance, and opens up a new avenue for measuring the effect of Parkinson's disease treatments on motor movement, allowing for better assessment of how effectively treatments restore motor activity.

neuroscience↗

bioRxiv2025

Reduced TRPC3 conductance underlies altered SNr activity under dopamine depletion: predictions from data-driven network models

Sufficient loss of dopamine within the basal ganglia (BG) leads to neuronal activity changes, including altered firing rates and firing patterns, thought to underlie parkinsonian motor symptoms. Yet, within BG neuronal populations, baseline activity and responses to inputs are highly variable, complicating efforts to identify key factors associated with pathological changes. We introduce a novel approach to constructing a computational neuron population model that, when applied to the mouse substantia nigra pars reticulata (SNr), captures the firing heterogeneity observed across slice and in vivo recordings. This model reproduces the diversity of SNr neuron responses to stimulation of GABAergic input terminals, yielding new insights into the mechanisms underlying this variability. Moreover, our modeling pinpoints significant decreases in TRPC3 conductance in SNr dendrites as a key determinant of altered SNr activity in the dopamine depleted state, with important implications for efforts to restore functional SNr activity in this condition. TeaserIn silico model capturing heterogeneity suggests factors behind SNr altered activity in dopamine depletion and responses to input

neuroscience↗

bioRxiv2024

Stimulation of the Medial SNr Promotes Sustained Motor Recovery and Counteracts Parkinsonian Pathophysiology in Dopamine Depleted Mice

Dopamine loss alters the activity of neural circuits in the basal ganglia, contributing to motor symptoms of Parkinsons disease and catalepsy. Treatments that reduce basal ganglia pathophysiology alleviate motor symptoms but require maintenance. Cell-type specific interventions can reduce pathophysiology and provide sustained therapeutic benefits, but a lack of understanding of pathways involved limits translation. Here, we establish patterns of neuromodulation and electrophysiological biomarkers at the level of basal ganglia output that predict the duration of therapeutic effects. Focal activation of neurons in the ventromedial substantia nigra reticulata (SNr) engaged a gradual recovery of movement that persisted for hours after treatment, accompanied by a persistent reduction in parkinsonian pathophysiology. Global SNr inhibition, as prescribed by the classic rate model, provided only transient effects on movement and did not reverse network pathophysiology. These findings represent important steps towards developing therapeutic strategies that aim to repair, rather than simply mask, circuit dysfunction in disease.

neuroscience↗

bioRxiv2020

A disynaptic circuit in the globus pallidus controls locomotion inhibition

Basal ganglia (BG) inhibit movement through two independent pathways, the indirect- and the hyperdirect-pathways. The globus pallidus (GP) has always been viewed as a simple relay within these two pathways, but its importance has changed drastically with the discovery of two functionally-distinct cell types, namely the prototypic and the arkypallidal neurons. Classic BG models suggest that all GP neurons receive GABAergic inputs from striato-pallidal indirect spiny projection neurons and glutamatergic inputs from subthalamic neurons. However, whether this synaptic connectivity scheme applies to both GP cell-types is currently unknown. Here, we optogenetically dissect the input organization of prototypic and arkypallidal neurons and further define the circuit mechanism underlying action inhibition in BG. Our results highlight that an increased activity of arkypallidal neurons is required to inhibit locomotion. Finally, this work supports the view that arkypallidal neurons are part of a novel disynaptic feedback loop that broadcast inhibitory control on movement execution.

neuroscience↗