Alterations in the intrinsic properties of striatal cholinergic interneurons after dopamine lesion and chronic L-DOPA
- Department of Psychiatry, Columbia University Medical Center, United States
- Department of Neurology, Grossman School of Medicine, New York University, United States
Figures
Figure 1 with 3 supplements
Changes in ChI spontaneous firing frequency induced by DA depletion followed by chronic L-DOPA treatment.
(A) DA lesion and chronic L-DOPA treatment paradigm. 3–4 weeks after unilateral 6-OHDA lesion, mice were randomly divided into two groups to receive either saline or L-DOPA. Experimental groups …
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Figure 1—source data 1
Individual neuron data and statistics for all panels and figure supplements.
- https://cdn.elifesciences.org/articles/56920/elife-56920-fig1-data1-v2.xlsx
Figure 1—figure supplement 1
Expression of L-DOPA-induced dyskinesia (LID) in 6-OHDA-lesioned mice.
(A) All 6-OHDA-lesioned mice developed contralateral front paw stepping deficits, p<0.0001 vs. 50% for both groups, Wilcoxon signed rank test. There was no difference in stepping deficit between the …
Figure 1—figure supplement 2
Burst-pause activity in ChIs.
The number and duration of bursts and pauses were quantitated using the robust Gaussian surprise method. (A–F) Firing patterns of ChIs from sham (n = 83 neurons/26 mice), 6-OHDA (n = 81 neurons/29 …
Figure 1—figure supplement 3
Basic electrophysiological characteristics in ChIs from control, 6-OHDA, and chronic LD mice.
(A) Voltage-current dependence, (B) resting membrane potential, (C) input resistance, (D) membrane capacitance and (F) rheobase were unchanged in 6-OHDA and chronic-LD groups. (E) Ramp protocol for …
Figure 2
Morphological parameters and synaptic inputs in ChIs from control, 6-OHDA lesioned and chronic LD mice.
(A–G) Sholl analysis of ChI morphology. Cells were filled with biocytin during physiological recordings, fixed, and imaged for biocytin labeling by confocal microscopy. (A) Representative maximum …
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Figure 2—source data 1
Individual neuron data and statistics for all panels.
- https://cdn.elifesciences.org/articles/56920/elife-56920-fig2-data1-v2.xlsx
Figure 3
HCN-mediated currents are decreased by 6-OHDA lesion.
(A) Representative perforated-patch recordings of sAP from sham, 6-OHDA and +chronic-LD groups. Dotted line represents a threshold potential, which was similar between the groups. Note the markedly …
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Figure 3—source data 1
Individual neuron data and statistics for all panels.
- https://cdn.elifesciences.org/articles/56920/elife-56920-fig3-data1-v2.xlsx
Figure 4
Changes in medium and slow afterhyperpolarization (AHP) currents.
(A and C) Representative voltage-clamp recording of (A) Ba2+-sensitive and (C) apamin-sensitive AHP currents before and after drug application (upper), and corresponding voltage protocols (lower). (B…
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Figure 4—source data 1
Individual neuron data and statistics for all panels.
- https://cdn.elifesciences.org/articles/56920/elife-56920-fig4-data1-v2.xlsx
Figure 5
Partial inhibition of HCN and SK channels is sufficient to mimic changes in ChI activity after lesion and chronic L-DOPA treatment.
(A) Proposed changes in HCN and SK currents in ChIs from different treatment groups and their effect on spontaneous firing rates (+). (B) Dependence of Ih density (as measured on Figure 3E) on …
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Figure 5—source data 1
Individual neuron data and statistics for all panels.
- https://cdn.elifesciences.org/articles/56920/elife-56920-fig5-data1-v2.xlsx
Tables
Key resources table
| Reagent type (species) or resource | Designation | Source or reference | Identifiers | Additional information |
|---|---|---|---|---|
| Strain, strain background (Mus musculus MF) | C57BL/6J mouse | Jackson Laboratory | IMSR Cat# JAX:000664, RRID:IMSR_JAX:000664 | |
| Genetic reagent (Mus musculus MF) | Chat-Cre; Tg(Chat-cre)GM24Gsat/Mmucd | GENSAT | RRID:MMRRC_017269-UCD | Colony maintained in-house |
| Genetic reagent (Mus musculus MF) | Ribotag; B6N.129-Rpl22tm1.1Psam/J | Jackson Laboratory | IMSR Cat# JAX:011029, RRID:IMSR_JAX:011029 | Colony maintained in-house |
| Chemical compound, drug | 6-OHDA ; 6-hydroxydopamine hydrobromide | Sigma Aldrich | Cat#:H-116 | |
| Chemical compound, drug | Desipramine hydrochloride | Sigma Aldrich | Cat#:D-3900 | |
| Chemical compound, drug | L-DOPA; L-3,4-dihydroxyphenylalanine methyl ester hydrochloride | Sigma Aldrich | Cat#:D-1507 | |
| Chemical compound, drug | Benserazide hydrochloride | Sigma Aldrich | Cat#:D-7283 | |
| Chemical compound, drug | TTX; tetrodotoxin citrate | Tocris | Cat#:1069 | |
| Chemical compound, drug | ZD7288 | Tocris | Cat#:1000 | |
| Chemical compound, drug | apamin | Tocris | Cat#:1652 | |
| Chemical compound, drug | CNQX; CNQX disodium salt | Tocris | Cat#:1045 | |
| Chemical compound, drug | AP5; DL-AP5 | Tocris | Cat#:0105 | |
| Chemical compound, drug | PCX; picrotoxin | Tocris | Cat#:1128 | |
| Chemical compound, drug | QX 314 bromide | Tocris | Cat#:1014 | |
| Chemical compound, drug | biocytin | Sigma-Aldrich | Cat#:B4261 | |
| Chemical compound, drug | dopamine; dopamine hydrochloride | Sigma-Aldrich | Cat#:H8502 | |
| Chemical compound, drug | BaCl2 | Sigma-Aldrich | Cat#:449644 | |
| Chemical compound, drug | gramicidin | Sigma-Aldrich | Cat#:G5002 | |
| Chemical compound, drug | streptavidin-DyLight-633 conjugate | Thermo Scientific | Cat:21844 | |
| Software, algorithm | WinWCP | University of Strathclyde, UK | RRID:SCR_014713 | http://spider.science.strath.ac.uk/sipbs/software_ses.htm |
| Software, algorithm | Pclamp10 | Molecular Devices | RRID:SCR_011323 | |
| Software, algorithm | Igor Pro 6 | WaveMetrics | RRID:SCR_000325 | |
| Software, algorithm | Mini Analysis | Synaptosoft | RRID:SCR_002184 | |
| Software, algorithm | Matlab 2016a, Matlab 2019a | MathWorks | RRID:SCR_001622 | |
| Software, algorithm | GraphPad Prism v8 | GraphPad | RRID:SCR_002798 |
