Differential impact of optogenetic stimulation of direct and indirect pathways from dorsolateral and dorsomedial striatum on motor symptoms in Huntington's disease mice

Experimental Neurology, Journal Year: 2024, Volume and Issue: 383, P. 114991 - 114991

Published: Oct. 9, 2024

The alterations in the basal ganglia circuitry are core pathological hallmark Huntington's Disease (HD) and traditionally linked to its sever motor symptoms. Recently it was shown that optogenetic stimulation of cortical afferences striatum is able reverse symptoms HD mice. However, specific contribution direct indirect striatal output pathways from dorsolateral (DLS) dorsomedial (DMS) phenotype still not clear. Here, we aim uncover contributions these subcircuits control wild type (WT) mice by using symptomatic R6/1 We systematically evaluated locomotion, exploratory behavior, learning effects selective D1 or A2A expressing neurons (direct pathway, respectively), DLS DMS. Bilateral pathway DMS resulted subtle locomotor enhancements, while unaltering behavior. Additionally, bilateral improved performance accelerated rotarod task, suggesting a role learning. In contrast, mice, did modulate any behaviors. Overall, this study highlights have impact activity lack responses also suggests strategies involving cortico-striatal circuits rather than might be better strategy for managing movement disorders.

Language: Английский

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Context dependent contributions of the direct and indirect pathways in the associative and sensorimotor striatum

Published: March 21, 2024

To determine whether the contributions of striatal projection neurons from direct (dSPNs) and indirect (iSPNs) pathways basal ganglia to action selection locomotion can be generalized across associative (DMS) sensorimotor (DLS) striatum we compared optogenetic activation or inhibition these on different tests. We show that self-modulation dSPNs iSPNs in either compartment has opposite real-time place preference, selecting an DMS but not DLS. During reward seeking displacements, pathway both compartments, slows movement. spontaneous showed opposing effects depending modulated. Remarkably, DLS decreases while only facilitates displacements. These findings support a model opposite, complementary undescribed context.

Language: Английский

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Optogenetic Globus Pallidus Stimulation Improves Motor Deficits in 6-Hydroxydopamine-Lesioned Mouse Model of Parkinson’s Disease

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(9), P. 7935 - 7935

Published: April 27, 2023

Excessive inhibition of the external globus pallidus (GPe) by striatal GABAergic neurons is considered a central mechanism contributing to motor symptoms Parkinson's disease (PD). While electrophysiological findings support this view, behavioral studies assessing beneficial effects global GPe activations are scarce and reported results controversial. We used an optogenetic approach standard unilateral 6-hydroxydopamine nigrostriatal dopamine (DA) lesion model PD explore photostimulation on deficits in mice. Global was normal mice verify whether it reproduced typical impairment induced DA lesions. activation improved ipsilateral circling, contralateral forelimb akinesia, locomotor hypoactivity, bradykinesia 6-OHDA-lesioned at ineffective parameters (532 nm, 5 Hz, 3 mW) photoinhibition (450 12 had no effect activity use Bilateral 6 mW/side) reduced directed exploration working memory performances indicating that recruitment physiological conditions may depend task involved. Collectively, these shed new light functional role suggest promising target for neuromodulatory restoration PD.

Language: Английский

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Context dependent contributions of the direct and indirect pathways in the associative and sensorimotor striatum

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 21, 2024

Abstract To determine whether the contributions of striatal projection neurons from direct (dSPNs) and indirect (iSPNs) pathways basal ganglia to action selection locomotion can be generalized across associative (DMS) sensorimotor (DLS) striatum we compared optogenetic activation or inhibition these on different tests. We show that self-modulation dSPNs iSPNs in either compartment has opposite real-time place preference, selecting an DMS but not DLS. During reward seeking displacements, pathway both compartments, slows movement. spontaneous showed opposing effects depending modulated. Remarkably, DLS decreases while only facilitates displacements. These findings support a model opposite, complementary undescribed context.

Language: Английский

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Projections between the globus pallidus externa and cortex span motor and non-motor regions

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 9, 2024

Abstract The globus pallidus externa (GPe) is a heterogenous nucleus of the basal ganglia, with intricate connections to other ganglia nuclei, as well direct cortex. anatomic, molecular and electrophysiologic properties cortex-projecting pallidocortical neurons are not characterized. Here we show that project diverse motor non-motor cortical regions, organized topographically in GPe, segregate into two distinct electrophysiological phenotypes. In addition, find GPe receives synaptic input back from deep layers some which form reciprocal onto neurons. These results demonstrate existence fast, closed-loop circuit between cortex ideally positioned integrate information about behavioral goals, internal states, environmental cues rapidly modulate behavior.

Language: Английский

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