Stimulation of the Medial SNr Promotes Sustained Motor Recovery and Counteracts Parkinsonian Pathophysiology in Dopamine Depleted Mice DOI
Asier Aristieta, John E. Parker,

Mary D. Cundiff

et al.

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

Published: Dec. 15, 2024

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

Language: Английский

Rethinking the external globus pallidus and information flow in cortico-basal ganglia-thalamic circuits DOI Open Access
Cristina Giossi, Jonathan Rubin, Aryn H. Gittis

et al.

Authorea (Authorea), Journal Year: 2024, Volume and Issue: unknown

Published: April 13, 2024

For decades the external globus pallidus (GPe) has been viewed as a passive way-station in indirect pathway of cortico-basal ganglia-thalamic (CBGT) circuit, sandwiched between striatal inputs and basal ganglia outputs. According to this model, one-way descending signals amplify suppression downstream thalamic nuclei by inhibiting GPe activity. Here we revisit assumption, light new emerging work on cellular complexity, connectivity, functional role behavior. We show how, according circuit-level logic, is ideally positioned for relaying ascending control within ganglia. Focusing problem inhibitory control, illustrate how bidirectional flow information allows integration reactive proactive mechanisms during action selection. Taken together, evidence points being central hub CBGT participating linking multifaceted regulate

Language: Английский

Citations

4
Rethinking the external globus pallidus and information flow in cortico‐basal ganglia‐thalamic circuits DOI Creative Commons
Cristina Giossi, Jonathan Rubin, Aryn H. Gittis

et al.

European Journal of Neuroscience, Journal Year: 2024, Volume and Issue: 60(9), P. 6129 - 6144

Published: April 24, 2024

Abstract For decades, the external globus pallidus (GPe) has been viewed as a passive way‐station in indirect pathway of cortico‐basal ganglia‐thalamic (CBGT) circuit, sandwiched between striatal inputs and basal ganglia outputs. According to this model, one‐way descending signals amplify suppression downstream thalamic nuclei by inhibiting GPe activity. Here, we revisit assumption, light new emerging work on cellular complexity, connectivity functional role behaviour. We show how, according circuit‐level logic, is ideally positioned for relaying ascending control within ganglia. Focusing problem inhibitory control, illustrate how bidirectional flow information allows integration reactive proactive mechanisms during action selection. Taken together, evidence points being central hub CBGT participating linking multifaceted regulate

Language: Английский

Citations

4
In silico analysis of hub genes and regulatory networks implicates the putamen in non-motor Parkinson’s disease disorders DOI Creative Commons
Stephen Tunmise Akanbi, Joshua Ayodele Yusuf,

Thompson Oluwaferanmi Ayandele

et al.

Egyptian Journal of Medical Human Genetics, Journal Year: 2025, Volume and Issue: 26(1)

Published: Jan. 20, 2025

Abstract Background Parkinson’s disease (PD) is a neurodegenerative condition marked by the gradual degeneration of dopaminergic neurons in substantia nigra, leading to depletion nigra as well and decreased activity putamen. This study aims identify role putamen non-motor PD symptoms potential therapeutic target PD. Methods Transcriptome profiles (dataset number: GSE205450, obtained from postmortem caudate samples forty controls thirty-five patients) were retrieved Gene Expression Omnibus (GEO) database. Specifically, we focused on data for patients. Differential gene expression analysis was carried out using with Limma, filtering genes |logFC|> 1 (fold change) p < 0.05 ( -value). Protein–Protein Interaction networks constructed stringDB (combined score > 0.7) analyzed Cytoscape hub based various topological measures (EPC, MCC, MNC, Degree, EcCentricity). Enrichment conducted Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG). Also, transcription factor (TF)-hub networks, miRNA-hub association JASPAR database, Tarbase DisGeNET via NetworkAnalyst platform, respectively. Results Seven genes, namely SST , NPY IL6 PVALB ALB NTS TH identified Notable miRNAs included hsa-mir-34a-5p, hsa-mir-15a-5p, hsa-mir-424-5p, hsa-mir-19b-3p while key factors include GATA2, CREB1, FOXC1, FOXL1, TID1, NFKB1, YY1, SPIB, GATA3, STAT3 . Conclusions Our findings revealed close associations between such major depressive disorder, mood disorders schizophrenia. These may provide new direction developing therapy wet lab research encouraged.

Language: Английский

Citations

0
Brainstem Neuroadaptations in Rodent Models of Parkinson's Disease DOI Creative Commons

Racha Al Tannir,

Arnaud Pautrat,

Rémi Soutrenon

et al.

European Journal of Neuroscience, Journal Year: 2025, Volume and Issue: 61(7)

Published: March 31, 2025

ABSTRACT A classical theory of a key pathophysiological change in Parkinson's disease (PD) is that GABAergic neurons the substantia nigra pars reticulata (SNr), an output structure basal ganglia, become hyperactive following dopaminergic loss. Increased GABA release from SNr thus likely to induce neuroadaptations structures receiving direct projection SNr, including parabrachial nucleus (PBN), superior colliculus (SC), and periaqueductal gray (PAG). We have shown PBN indeed exhibits cellular molecular changes PD rat models. expected SC PAG likewise show neuroplasticity. The objective present work was evaluate plasticity both (lateral medial) rats with partial or total lesion. used Golgi–Cox measure spine density morphology Western blot analyze receptor expression models compared sham animals. found increase (thin stubby types) lesions PAG. Additionally, increased observed lateral lesion group only. These results suggest compensatory mechanisms may delay onset contribute motor nonmotor symptoms. Further investigation should be performed fully understand functional impact revealed this work.

Language: Английский

Citations

0
Segregated basal ganglia output pathways correspond to genetically divergent neuronal subclasses DOI
Alana I. Mendelsohn,

Laudan Nikoobakht,

Jay B. Bikoff

et al.

Cell Reports, Journal Year: 2025, Volume and Issue: 44(4), P. 115454 - 115454

Published: March 27, 2025

Language: Английский

Citations

0
Activating Striatal Parvalbumin Interneurons to Alleviate Chemotherapy‐Induced Muscle Atrophy DOI Creative Commons
Jun Hu, Jingyuan Liu, Yuqing Yan

et al.

Journal of Cachexia Sarcopenia and Muscle, Journal Year: 2025, Volume and Issue: 16(2)

Published: April 1, 2025

Language: Английский

Citations

0
Dopamine depletion weakens direct pathway modulation of SNr neurons DOI Creative Commons
Asier Aristieta, John E. Parker, Ya Gao

et al.

Neurobiology of Disease, Journal Year: 2024, Volume and Issue: 196, P. 106512 - 106512

Published: April 24, 2024

Neurons in the substantia nigra reticulata (SNr) transmit information about basal ganglia output to dozens of brain regions thalamocortical and brainstem motor networks. Activity SNr neurons is regulated by convergent input from upstream nuclei, including GABAergic inputs striatum external globus pallidus (GPe). convey direct pathway, while GPe indirect pathway. Chronic loss dopamine, as occurs Parkinson's disease, disrupts balance pathway at level striatum, but question how dopamine affects propagation along these pathways outside less well understood. Using a combination vivo slice electrophysiology, we find that depletion selectively weakens pathway's influence over neural activity due changes decay kinetics GABA-mediated synaptic currents. signaling was not affected, resulting an inversion normal inhibitory control through SNr. These results highlight contribution cellular mechanisms impact responses disease.

Language: Английский

Citations

3
Tonic dendritic GABA release by substantia nigra dopaminergic neurons DOI Open Access
DeNard V. Simmons, Oscar Andrés Moreno-Ramos, Divya Raj

et al.

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

Published: March 30, 2024

Abstract Recent studies have demonstrated the importance of extrastriatal dopamine release in emergence network dysfunction underlying motor deficits Parkinson’s disease (PD). To better characterize actions on substantia nigra pars reticulata (SNr) GABAergic neurons, optogenetic and electrophysiological tools were used ex vivo mouse brain slices to monitor synaptic transmission arising from globus pallidus externa (GPe) neurons. As predicted by previous work, activation D2 receptors (D2Rs) suppressed GABA evoked stimulation GPe axons. However, D2R also a tonic, A receptor-mediated inhibition SNr spiking. D2R-mediated tonic led roughly 30% increase spiking rate. Chemogenetic terminals or excitation astrocytes did not affect SNr. In contrast, chemogenetic dopaminergic neurons knocking down expression aldehyde dehydrogenase 1A1 (ALDH1A1) blunted signaling. Antagonizing D1 striatonigral modestly increased Lastly, progressive model PD targeting was lost. Taken together, these observations suggest that are co-released dendrites ALDH1A1-expressing course through The co-release transmitters could serve promote movement making less responsive phasic activity indirect pathway circuitry lowering basal rates.

Language: Английский

Citations

1
Segregated basal ganglia output pathways correspond to genetically divergent neuronal subclasses DOI Creative Commons
Alana I. Mendelsohn,

Laudan Nikoobakht,

Jay B. Bikoff

et al.

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

Published: Aug. 29, 2024

The basal ganglia control multiple sensorimotor behaviors though anatomically segregated and topographically organized subcircuits with outputs to specific downstream circuits. However, it is unclear how the anatomical organization of output circuits relates molecular diversity cell types. Here, we demonstrate that major nucleus ganglia, substantia nigra pars reticulata (SNr) comprised transcriptomically distinct subclasses reflect its progenitor lineages. We show these are within SNr, project targets in midbrain hindbrain, receive inputs from different striatal subregions. Finally, mouse also identifiable human SNr neurons, suggesting genetic evolutionarily conserved. These findings provide a unifying logic for developmental specification diverse neurons controlling specialized brain regions.

Language: Английский

Citations

1
Chronic alcohol induces subcircuit-specific striatonigral plasticity enhancing the sensorimotor basal ganglia role in action execution DOI Creative Commons
Giacomo Sitzia, Sebastiano Bariselli, Alexa L. Gracias

et al.

Science Advances, Journal Year: 2024, Volume and Issue: 10(26)

Published: June 28, 2024

Functional deficits in basal ganglia (BG) circuits contribute to cognitive and motor dysfunctions alcohol use disorder. Chronic exposure alters synaptic function neuronal excitability the dorsal striatum, but it remains unclear how affects BG output that is mediated by substantia nigra pars reticulata (SNr). Here, we describe a subpopulation-specific organization of striatal subthalamic (STN) inputs medial lateral SNr. (CIE) potentiated dorsolateral striatum (DLS) did not change dorsomedial STN Chemogenetic inhibition DLS direct pathway neurons revealed an enhanced role for execution instrumental lever-pressing task. Overall, reveal subregion-specific onto SNr find DLS-SNr are accompanied altered control action following CIE.

Language: Английский

Citations

0