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Alterations in the intrinsic properties of striatal cholinergic interneurons after dopamine lesion and chronic L-DOPA
- Source :
- eLife, eLife, Vol 9 (2020)
- Publication Year :
- 2020
- Publisher :
- Cold Spring Harbor Laboratory, 2020.
-
Abstract
- SummaryChanges in striatal cholinergic interneuron (ChI) activity are thought to contribute to Parkinson’s disease pathophysiology and dyskinesia from chronic L-3,4-dihydroxyphenylalanine (L-DOPA) treatment, but the physiological basis of these changes are unknown. We find that dopamine lesion decreases the spontaneous firing rate of ChIs, whereas chronic treatment with L-DOPA of lesioned mice increases baseline ChI firing rates to levels beyond normal activity. The effect of dopamine loss on ChIs was due to decreased currents of both hyperpolarization-activated cyclic nucleotide-gated (HCN) and small conductance calcium-activated potassium (SK) channels. L-DOPA reinstatement of dopamine normalized HCN activity, but SK current remained depressed. Pharmacological blockade of HCN and SK activities mimicked changes in firing, confirming that these channels are responsible for the molecular adaptation of ChIs to dopamine loss and chronic L-DOPA treatment. These findings suggest that targeting ChIs with channel-specific modulators may provide therapeutic approaches for alleviating L-DOPA-induced dyskinesia in PD patients.
- Subjects :
- Male
Parkinson's disease
Mouse
Small-Conductance Calcium-Activated Potassium Channels
Dopamine
striatum
Striatum
Levodopa
Mice
Random Allocation
0302 clinical medicine
Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
Biology (General)
0303 health sciences
SK
General Neuroscience
spontaneous firing
General Medicine
Cholinergic Neurons
HCN
Pathophysiology
3. Good health
medicine.anatomical_structure
Medicine
medicine.symptom
Research Article
medicine.drug
medicine.medical_specialty
Interneuron
QH301-705.5
Science
General Biochemistry, Genetics and Molecular Biology
Lesion
03 medical and health sciences
Interneurons
Internal medicine
medicine
Animals
030304 developmental biology
General Immunology and Microbiology
business.industry
medicine.disease
electrophysiology
Corpus Striatum
Blockade
Mice, Inbred C57BL
Electrophysiology
Endocrinology
Dyskinesia
parkinson's disease
Cholinergic
business
030217 neurology & neurosurgery
Neuroscience
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- eLife, eLife, Vol 9 (2020)
- Accession number :
- edsair.doi.dedup.....0dbc5a8dcd0bbf987bc702923cfee42f