Targeting parvalbumin-expressing neurons in the substantia nigra pars reticulata restores motor function in parkinsonian mice
Summary: The activity of substantia nigra pars reticulata (SNr) neurons, the main output structure of basal ganglia, is altered in Parkinson’s disease (PD). However, neither the underlying mechanisms nor the type of neurons responsible for PD-related motor dysfunctions have been elucidated yet. Here...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-10-01
|
| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723012998 |
| _version_ | 1827793557950300160 |
|---|---|
| author | Lorena Delgado-Zabalza Nicolas P. Mallet Christelle Glangetas Guillaume Dabee Maurice Garret Cristina Miguelez Jérôme Baufreton |
| author_facet | Lorena Delgado-Zabalza Nicolas P. Mallet Christelle Glangetas Guillaume Dabee Maurice Garret Cristina Miguelez Jérôme Baufreton |
| author_sort | Lorena Delgado-Zabalza |
| collection | DOAJ |
| description | Summary: The activity of substantia nigra pars reticulata (SNr) neurons, the main output structure of basal ganglia, is altered in Parkinson’s disease (PD). However, neither the underlying mechanisms nor the type of neurons responsible for PD-related motor dysfunctions have been elucidated yet. Here, we show that parvalbumin-expressing SNr neurons (SNr-PV+) occupy dorsolateral parts and possess specific electrophysiological properties compared with other SNr cells. We also report that only SNr-PV+ neurons’ intrinsic excitability is reduced by downregulation of sodium leak channels in a PD mouse model. Interestingly, in anesthetized parkinsonian mice in vivo, SNr-PV+ neurons display a bursty pattern of activity dependent on glutamatergic tone. Finally, we demonstrate that chemogenetic inhibition of SNr-PV+ neurons is sufficient to alleviate motor impairments in parkinsonian mice. Overall, our findings establish cell-type-specific dysfunction in experimental parkinsonism in the SNr and provide a potential cellular therapeutic target to alleviate motor symptoms in PD. |
| first_indexed | 2024-03-11T18:19:10Z |
| format | Article |
| id | doaj.art-7eb0caa0e63640a6b7a2a9a94bd442a5 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-11T18:19:10Z |
| publishDate | 2023-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-7eb0caa0e63640a6b7a2a9a94bd442a52023-10-16T04:12:12ZengElsevierCell Reports2211-12472023-10-014210113287Targeting parvalbumin-expressing neurons in the substantia nigra pars reticulata restores motor function in parkinsonian miceLorena Delgado-Zabalza0Nicolas P. Mallet1Christelle Glangetas2Guillaume Dabee3Maurice Garret4Cristina Miguelez5Jérôme Baufreton6University Bordeaux, CNRS, IMN, UMR 5293, 33000 Bordeaux, France; Department of Pharmacology. University of the Basque Country (UPV/EHU), 48940 Leioa, SpainUniversity Bordeaux, CNRS, IMN, UMR 5293, 33000 Bordeaux, FranceUniversity Bordeaux, CNRS, IMN, UMR 5293, 33000 Bordeaux, FranceUniversity Bordeaux, CNRS, IMN, UMR 5293, 33000 Bordeaux, FranceUniversity Bordeaux, CNRS, INCIA, UMR 5287, 33000 Bordeaux, FranceDepartment of Pharmacology. University of the Basque Country (UPV/EHU), 48940 Leioa, Spain; Autonomic and Movement Disorders Unit, Neurodegenerative Diseases, Biocruces Health Research Institute, Barakaldo, SpainUniversity Bordeaux, CNRS, IMN, UMR 5293, 33000 Bordeaux, France; Corresponding authorSummary: The activity of substantia nigra pars reticulata (SNr) neurons, the main output structure of basal ganglia, is altered in Parkinson’s disease (PD). However, neither the underlying mechanisms nor the type of neurons responsible for PD-related motor dysfunctions have been elucidated yet. Here, we show that parvalbumin-expressing SNr neurons (SNr-PV+) occupy dorsolateral parts and possess specific electrophysiological properties compared with other SNr cells. We also report that only SNr-PV+ neurons’ intrinsic excitability is reduced by downregulation of sodium leak channels in a PD mouse model. Interestingly, in anesthetized parkinsonian mice in vivo, SNr-PV+ neurons display a bursty pattern of activity dependent on glutamatergic tone. Finally, we demonstrate that chemogenetic inhibition of SNr-PV+ neurons is sufficient to alleviate motor impairments in parkinsonian mice. Overall, our findings establish cell-type-specific dysfunction in experimental parkinsonism in the SNr and provide a potential cellular therapeutic target to alleviate motor symptoms in PD.http://www.sciencedirect.com/science/article/pii/S2211124723012998CP: Neuroscience |
| spellingShingle | Lorena Delgado-Zabalza Nicolas P. Mallet Christelle Glangetas Guillaume Dabee Maurice Garret Cristina Miguelez Jérôme Baufreton Targeting parvalbumin-expressing neurons in the substantia nigra pars reticulata restores motor function in parkinsonian mice Cell Reports CP: Neuroscience |
| title | Targeting parvalbumin-expressing neurons in the substantia nigra pars reticulata restores motor function in parkinsonian mice |
| title_full | Targeting parvalbumin-expressing neurons in the substantia nigra pars reticulata restores motor function in parkinsonian mice |
| title_fullStr | Targeting parvalbumin-expressing neurons in the substantia nigra pars reticulata restores motor function in parkinsonian mice |
| title_full_unstemmed | Targeting parvalbumin-expressing neurons in the substantia nigra pars reticulata restores motor function in parkinsonian mice |
| title_short | Targeting parvalbumin-expressing neurons in the substantia nigra pars reticulata restores motor function in parkinsonian mice |
| title_sort | targeting parvalbumin expressing neurons in the substantia nigra pars reticulata restores motor function in parkinsonian mice |
| topic | CP: Neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723012998 |
| work_keys_str_mv | AT lorenadelgadozabalza targetingparvalbuminexpressingneuronsinthesubstantianigraparsreticulatarestoresmotorfunctioninparkinsonianmice AT nicolaspmallet targetingparvalbuminexpressingneuronsinthesubstantianigraparsreticulatarestoresmotorfunctioninparkinsonianmice AT christelleglangetas targetingparvalbuminexpressingneuronsinthesubstantianigraparsreticulatarestoresmotorfunctioninparkinsonianmice AT guillaumedabee targetingparvalbuminexpressingneuronsinthesubstantianigraparsreticulatarestoresmotorfunctioninparkinsonianmice AT mauricegarret targetingparvalbuminexpressingneuronsinthesubstantianigraparsreticulatarestoresmotorfunctioninparkinsonianmice AT cristinamiguelez targetingparvalbuminexpressingneuronsinthesubstantianigraparsreticulatarestoresmotorfunctioninparkinsonianmice AT jeromebaufreton targetingparvalbuminexpressingneuronsinthesubstantianigraparsreticulatarestoresmotorfunctioninparkinsonianmice |