Early structural and functional plasticity alterations in a susceptibility period of DYT1 dystonia mouse striatum
- University of Rome Tor Vergata, Italy
- IRCCS Fondazione Santa Lucia, Italy
- University of Milan, Italy
Figures
Figure 1
Electrophysiological and synaptic properties of striatal SPNs.
(A) Superimposed traces showing voltage responses to both depolarizing (+600 pA) and hyperpolarizing (−200 pA) current steps in SPNs recorded from P26 Tor1a+/+ (black) and Tor1a+/Δgag (red) mice. …
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Figure 1—source data 1
Electrophysiological and synaptic properties of striatal SPNs.
- https://doi.org/10.7554/eLife.33331.003
Figure 2
Altered developmental profile of corticostriatal long-term synaptic plasticity expression in Tor1a+/Δgag mice.
(A) (Top) Developmental time-course of LTD expression in Tor1a+/+ mice. HFS protocol (arrow) induces LTD in SPNs recorded from Tor1a+/+ mice after P28 (59.63 ± 2.63% of control; N = 8, n = 8; paired …
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Figure 2—source data 1
Altered developmental profile of corticostriatal long-term synaptic plasticity expression in Tor1a+/Δgag mice.
- https://doi.org/10.7554/eLife.33331.005
Figure 3
Electrophysiological characterization of AMPAR and NMDAR currents at corticostriatal synapses of SPNs in both Tor1a+/+ and Tor1a+/Δgag mice.
(A) (Left) Representative EPSCs traces recorded at HP=+40 mV from SPNs of juvenile Tor1a+/+ and Tor1a+/Δgag mice. The NMDAR antagonist MK-801 isolates the AMPAR-mediated EPSC component (black …
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Figure 3—source data 1
Electrophysiological characterization of AMPAR and NMDAR currents at corticostriatal synapses of SPNs in both Tor1a+/+ and Tor1a+/Δgag mice.
- https://doi.org/10.7554/eLife.33331.007
Figure 4
Molecular analysis of the SPNs postsynaptic compartment in P26 and P60 Tor1a+/Δgag compared to age-matched wild-type mice.
WB analyses were performed on the post-synaptic TIF fraction in a minimum of three different animals per genotype. (A) WB analysis for GluN2A, GluN2B, PSD-95 and tubulin in P26 (left panel) and P60 …
Figure 5
Analysis of dendritic spines morphology in P26 and P60 Tor1a+/Δgag compared to age-matched Tor1a+/+mice.
(A) Histogram representing dendritic spine density in P26 Tor1a+/Δgag and Tor1a+/+ mice (Tor1a+/+, 10.25 ± 0.75 spines/10 μm, n = 10; Tor1a+/Δgag, 7.89 ± 0.70 spines/10 μm, n = 10; unpaired …
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Figure 5—source data 1
Analysis of dendritic spines morphology in P26 Tor1a+/Δgag compared to age-matched Tor1a+/+ mice.
- https://doi.org/10.7554/eLife.33331.010
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Figure 5—source data 2
Analysis of dendritic spines morphology in P60 Tor1a+/Δgag compared to age-matched Tor1a+/+ mice.
- https://doi.org/10.7554/eLife.33331.011
Figure 6
BDNF protein expression in the striatum of Tor1a+/+and Tor1a+/Δgag mice.
(A, B) Striatal BDNF protein expression in Tor1a+/+ and Tor1a+/Δgag mice at postnatal stages (P15, P26, P60). The graphs show the quantification of BDNF/proBDNF ratio at the various ages. Data are …
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Figure 6—source data 1
BDNF protein expression in the striatum of Tor1a+/+ and Tor1a+/Δgag mice.
- https://doi.org/10.7554/eLife.33331.013
Figure 7
In vivo ANA-12 treatment rescues synaptic plasticity deficits in juvenile Tor1a+/Δgag mice.
(A) Time-course of corticostriatal LTD in juvenile Tor1a+/+ and Tor1a+/Δgag mice (P28-35): after in vivo treatment with the TrkB antagonist ANA-12, the HFS protocol (arrow) induces corticostriatal …
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Figure 7—source data 1
In vivo ANA-12 treatment rescues synaptic plasticity deficits in juvenile Tor1a+/Δgag mice.
- https://doi.org/10.7554/eLife.33331.015
Tables
Key resources table
| Reagent type (species) or resource | Designation | Source or reference | Identifiers | Additional information |
|---|---|---|---|---|
| Gene (Mus musculus) | Tor1a | MGI:1353568 | Gene ID: 30931 | official full name: torsin family 1, member A (torsin A) |
| Strain, strain background (M. musculus) | C57BL/6J mice | Charles River | catalog number B6JSIFE10SZ - C57BL/6J SPF/VAF; RRID:IMSR_JAX:000664 | |
| Genetic reagent (M. musculus) | heterozygous knock-in Tor1a+/Δgag | Goodchild et al. (2005) | - | maintained on the C57BL/6J background |
| Antibody | monoclonal anti-PSD-95 | Neuromab | clone (k28/43) - catalog number 75–028; RRID:AB_2292909 | dilution 1:2000 in I-Block |
| Antibody | monoclonal anti-GluN2B | Neuromab | clone 59/20 - catalog number 75–097; RRID:AB_10673405 | dilution 1:1000 in I-Block |
| Antibody | polyclonal anti-GluA1 | Merck Millipore | catalog number AB1504; RRID:AB_2113602 | dilution 1:1000 in I-Block |
| Antibody | polyclonal anti-phospho-GluA1 (Ser845) | Merck Millipore | catalog number 04–1073; RRID:AB_1977219 | dilution 1:1000 in I-Block |
| Antibody | polyclonal anti-GluN2A | Sigma-Aldrich | catalog number M264 RRID:AB_260485 | dilution 1:1000 in I-Block |
| Antibody | monoclonal anti-GluA2 | Neuromab | clone L21/32 - catalog number 75–002; RRID:AB_2232661 | dilution 1:1000 in I-Block |
| Antibody | monoclonal anti-α-tubulin | Sigma-Aldrich | clone DM1A - catalog number T9026; RRID:AB_477593 | dilution 1:5000 in I-Block |
| Antibody | goat anti-DARPP-32 | R and D system | catalog number AF6259; RRID:AB_10641854 | dilution 1:500 in I-Block |
| Antibody | mouse anti-Enkephalin | Millipore | catalog number MAB350; RRID:AB_2268028 | dilution 1:1000 in I-Block |
| Antibody | mouse anti-β-actin | Sigma Aldrich | catalog number A5441; RRID:AB_476744 | dilution 1:20000 in I-Block |
| Commercial assay or kit | Clarity Western ECL Substrate | BioRad | - | reagent used to visualize protein bands with Chemidoc Imaging System |
| Commercial assay or kit | ECL reagent | GEHealthcare | catalog number GERPN2232 | reagent used to visualize protein bands with membranes were exposed to film |
| Commercial assay or kit | TRI-reagent | Sigma Aldrich | catalog number T9424 | reagent used to RNA extraction |
| Commercial assay or kit | DNAase I | Invitrogen | catalog number AMPD1-1KT | reagent used for elimination of DNA from RNA |
| Commercial assay or kit | Transcriptor First Strand cDNA Synthesis Kit | Roche | catalog number04379012001 | reagent used to reverse transcribe RNA |
| Commercial assay or kit | Extract-N-Amp™ Tissue PCR Kit | SIGMA | catalog number XNAT2 | genotyping primers UP- AGT CTG TGG CTG GCT CTC C; Low- CCT CAG GCTGCT CAC AAC C |
| Chemical compound, drug | ANA-12 | Sigma-Aldrich | catalog number SML0209 | in vivo administration |
| Chemical compound, drug | CNQX disodium salt | Tocris | catalog number 0190/10 | application in bath during electrophysiology analysis |
| Chemical compound, drug | (+)-MK 801 maleate | Tocris | catalog number 0924/10 | application in bath during electrophysiology analysis |
| Chemical compound, drug | Tetrodotoxin citrate (TTX) | Tocris | catalog number 1069/1 | application in bath during electrophysiology analysis |
| Chemical compound, drug | Picrotoxin | Tocris | catalog number 1128/1 | application in bath during electrophysiology analysis |
| Chemical compound, drug | Biocytin | Tocris | catalog number 3349/10 | electrodes filled with biocytin, versatile marker used for neuroanatomical investigations of neuron IHC |
| Chemical compound, drug | Naspm trihydrochloride | Tocris | catalog number 2766/10 | application in bath during electrophysiology analysis |
| Software, algorithm | ImageLab | BioRad | - | software used for quantification of protein bands in western blotting experiments |
| Software, algorithm | ImageJ software | NIH;Schneider et al. (2012) | RRID:SCR_003070 | software used for the quantification of protein bands in western blotting and confocal laser scanning microscope |
| Software, algorithm | ClampFit 9 | pClamp | Molecular Devices; RRID:SCR_011323 | data analysis |
| Software, algorithm | Origin 8.0 | Microcal | RRID:SCR_002815 | data analysis |
| Software, algorithm | Prism 5.3 | GraphPad | RRID:SCR_002798 | data analysis |
Additional files
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Transparent reporting form
- https://doi.org/10.7554/eLife.33331.016
