Oxytocin neurons mediate the effect of social isolation via the VTA circuits
- Department of Basic Neuroscience, University of Geneva, Switzerland
- Laboratory of Child Growth and Development, University of Geneva, Switzerland
- Division of Neonatology and Pediatric Intensive Care, Children's University Hospital of Geneva, Switzerland
Figures
Figure 1 with 3 supplements
Adolescence acute social isolation induces social craving.
(A) Experimental design: WT mice were isolated between P28 and P35 or kept in group. After isolation, mice (from different cohorts) were subjected to different behavioral task. (B) Free direct …
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Figure 1—source data 1
Figure 1 - raw data and statistical output.
- https://cdn.elifesciences.org/articles/73421/elife-73421-fig1-data1-v2.xlsx
Figure 1—figure supplement 1
Effects of social isolation on social behavior.
(A) Experimental design: WT mice were isolated for 24 hr between P34 and P35 or kept in group. After isolation, mice were subjected to free direct interaction task paradigm. (B) Time exploring …
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Figure 1—figure supplement 1—source data 1
Figure 1—figure supplement 1 - raw data and statistical output.
- https://cdn.elifesciences.org/articles/73421/elife-73421-fig1-figsupp1-data1-v2.xlsx
Figure 1—figure supplement 2
Effects of social isolation on social behavior.
(A) Experimental design: WT mice were isolated between P28 and P35 or kept in group. After isolation, mice were subjected to Novel object recognition (NORT) and Elevated plus maze (same cohorts). (B)…
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Figure 1—figure supplement 2—source data 1
Figure 1—figure supplement 2 - raw data and statistical output.
- https://cdn.elifesciences.org/articles/73421/elife-73421-fig1-figsupp2-data1-v2.xlsx
Figure 1—figure supplement 3
Effects of social isolation during adulthood.
(A) Experimental design: WT mice were isolated between P53 and P60 or kept in group. After isolation, mice were subjected to different behavioral task. (B) Free direct interaction task paradigm. (C) …
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Figure 1—figure supplement 3—source data 1
Figure 1—figure supplement 3 - raw data and statistical output.
- https://cdn.elifesciences.org/articles/73421/elife-73421-fig1-figsupp3-data1-v2.xlsx
Figure 2
Adolescence acute social isolation induces putative VTA DA neurons hyperexcitability.
(A) Experimental design: WT mice were isolated between P28 and P35 or kept in group. After isolation, mice were subjected whole-cell patch-clamp recordings. (B) Left: experimental paradigm, putative …
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Figure 2—source data 1
Figure 2 - raw data and statistical output.
- https://cdn.elifesciences.org/articles/73421/elife-73421-fig2-data1-v2.xlsx
Figure 3 with 1 supplement
PVN OXT neurons as main orchestrator of social isolation induced social craving.
(A) Representative confocal images of PVN stained with cFOS, OXT, and AVP antibody (scale bar: 20 µm). (B) cFos+ cells (as % of DAPI+ cells) (Unpaired samples t-test, t(22)=2.510, p=0.0199, n=12 …
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Figure 3—source data 1
Figure 3 - raw data and statistical output.
- https://cdn.elifesciences.org/articles/73421/elife-73421-fig3-data1-v2.xlsx
Figure 3—figure supplement 1
CNO validation.
(A) Experimental design: WT mice were isolated between P28 and P35 or kept in group. After isolation, mice were perfused and brain slices were immunostained with cFOS, OXT, and AVP antibody. (B) PVN …
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Figure 3—figure supplement 1—source data 1
Figure 3—figure supplement 1 - raw data and statistical output.
- https://cdn.elifesciences.org/articles/73421/elife-73421-fig3-figsupp1-data1-v2.xlsx
Figure 4 with 2 supplements
Long-lasting effects of adolescence acute social isolation.
(A) Experimental design: WT mice were isolated between P28 and P35 and regrouped until P60 or always kept in group. Mice (different cohorts) were subjected to different behavioral tasks. (B) …
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Figure 4—source data 1
Figure 4 - raw data and statistical output.
- https://cdn.elifesciences.org/articles/73421/elife-73421-fig4-data1-v2.xlsx
Figure 4—figure supplement 1
Long-lasting effects of acute social isolation in adolescence.
(A) Experimental design: WT mice were isolated between P28 and P35 and regrouped until P60 or always kept in group. (B) Three-chamber task experimental paradigm. (C) Time in chamber during social …
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Figure 4—figure supplement 1—source data 1
Figure 4—figure supplement 1 - raw data and statistical output.
- https://cdn.elifesciences.org/articles/73421/elife-73421-fig4-figsupp1-data1-v2.xlsx
Figure 4—figure supplement 2
Regrouping after adolescence social isolation restore PVN and VTA excitability.
(A) Experimental design: WT mice were isolated between P28 and P35 and regrouped until P60 or always kept in group. CTB-488 was injected at p45-50. (B) Left: experimental paradigm, PVN neurons were …
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Figure 4—figure supplement 2—source data 1
Figure 4—figure supplement 2 - raw data and statistical output.
- https://cdn.elifesciences.org/articles/73421/elife-73421-fig4-figsupp2-data1-v2.xlsx
Figure 5 with 2 supplements
Adolescence acute social isolation induces synaptic scaling in adulthood mice.
(A, B, G) Experimental paradigm. WT mice were isolated between P28 and P35. Then mice were regrouped, injected with 488-CTB in the mPFC (B) or NAc (G) between P45–P50 and at P60 were subjected at …
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Figure 5—source data 1
Figure 5 - raw data and statistical output.
- https://cdn.elifesciences.org/articles/73421/elife-73421-fig5-data1-v2.xlsx
Figure 5—figure supplement 1
Adolescence acute social isolation induces synaptic scaling in VTA pDA-mPFC projecting neruons.
(A, B, G) Experimental paradigm. WT mice were injected with 488-CTB in the mPFC (B) or NAc (G) at P21 and isolated between P28 and P35. Then mice were subjected at whole-cell patch-clamp recording. …
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Figure 5—figure supplement 1—source data 1
Figure 5—figure supplement 1 - raw data and statistical output.
- https://cdn.elifesciences.org/articles/73421/elife-73421-fig5-figsupp1-data1-v2.xlsx
Figure 5—figure supplement 2
Immunohistochemical validation of VTA-DA neurons.
(A) Example of VTA horizontal slice. (B) Confocal images of post hoc immunohistochemical validation of VTA neurons filled with GFP (Alexa Fluor 488) and stained with TH-antibody. The white arrow …
Figure 6
CP-AMPARs are responsible of increased social interaction during adulthood.
(A) Experimental paradigm: WT mice were isolated between P28 and P35. Then mice were regrouped until P53 and canulated over the VTA. (B) Mice underwent to direct free interaction task after infusion …
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Figure 6—source data 1
Figure 6 - raw data and statistical output.
- https://cdn.elifesciences.org/articles/73421/elife-73421-fig6-data1-v2.xlsx
Figure 7
Graphical summary.
One week of social isolation during adolescence in mice increased social interaction at the expense of social habituation and social novelty preference. Behavioral changes were accompanied by the …
Tables
Key resources table
| Reagent type (species) or resource | Designation | Source or reference | Identifiers | Additional information |
|---|---|---|---|---|
| Chemical compound, drug | Choline chloride | Sigma-Aldrich | C7527 | |
| Chemical compound, drug | D-(+)-Glucose | Sigma-Aldrich | G8270 | |
| Chemical compound, drug | D(+)-Saccharose | Roth | 4621.1 | |
| Chemical compound, drug | NaHCO3 | Sigma-Aldrich | S5761 | |
| Chemical compound, drug | MgCl2 | Sigma-Aldrich | 63068 | |
| Chemical compound, drug | Ascorbic acid | Roth | 6288.1 | |
| Chemical compound, drug | Sodium pyruvate | Roth | 8793.1 | |
| Chemical compound, drug | KCl | Sigma-Aldrich | 60130 | |
| Chemical compound, drug | NaH2PO4 | Sigma-Aldrich | S0751 | |
| Chemical compound, drug | CaCl2 | Sigma-Aldrich | 21097 | |
| Chemical compound, drug | NaCl | Sigma-Aldrich | 31434 | |
| Chemical compound, drug | K-Gluconate | Sigma-Aldrich | G4500 | |
| Chemical compound, drug | EGTA | Sigma-Aldrich | E4378 | |
| Chemical compound, drug | HEPES | Sigma-Aldrich | H3375 | |
| Chemical compound, drug | Na2ATP | Sigma-Aldrich | A2383 | |
| Chemical compound, drug | Na3GTP | Sigma-Aldrich | G8877 | |
| Chemical compound, drug | Creatine-phosphate | Sigma-Aldrich | P7936 | |
| Chemical compound, drug | CsCl | Sigma-Aldrich | 20966 | |
| Chemical compound, drug | Sodium creatine phosphate | Sigma-Aldrich | 27920 | |
| Chemical compound, drug | Spermine | Sigma-Aldrich | S4264 | |
| Chemical compound, drug | Lidocaine N-ethyl bromide (QX-314) | Sigma-Aldrich | L5783 | |
| Chemical compound, drug | NaOH | Sigma-Aldrich | S5881 | |
| Chemical compound, drug | Clozapine N-oxide | Enzo Life | BML-NS-105-0025 | 5 mg/200 ml |
| Chemical compound, drug | Saccharin | Sigma-Aldrich | 240931 | |
| Chemical compound, drug | NASPM | Tocris | 2766 | |
| Chemical compound, drug | NGS | Sigma-Aldrich | AB7481 | |
| Chemical compound, drug | Triton X-100 | Sigma-Aldrich | X100 | |
| Chemical compound, drug | Kynurenic acid | Sigma-Aldrich | K3375 | |
| Chemical compound, drug | Picrotoxin | Tocris | 1128 | |
| Chemical compound, drug | D-APV | Tocris | 106 | |
| Antibody | Oxytocin antibody (guinea pig polyclonal) | Synaptic Systems | #408004 | (1:500) |
| Antibody | cFOS antibody (rabbit monoclonal) | Synaptic Systems | #226008 | (1:5000) |
| Antibody | Neurophysin 2/NP-AVP antibody (mouse monoclonal) | Merck Millipore | #MABN856 | (1:250) |
| Antibody | HA-tag (6E2) antibody (mouse monoclonal) | Cell Signaling Technology | #2367 | (1:200) |
| Antibody | Oxytocin antibody (rabbit polyclonal) | Merck Millipore | #AB911 | (1:500) |
| Antibody | Tyrosine Hydroxylase antibody (mouse monoclonal) | Merck Millipore | #MAB318 | (1:500) |
| Antibody | Goat anti-mouse Alexa Fluor 555 (polyclonal) | Thermo Fisher Scientific | A21422 | (1:500) |
| Antibody | Goat anti-rabbit Alexa Fluor 488 (polyclonal) | Thermo Fisher Scientific | A11008 | (1:500) |
| Antibody | Goat anti-mouse Alexa Fluor 594 (polyclonal) | Thermo Fisher Scientific | A11005 | (1:500) |
| Antibody | Goat anti-mouse Alexa Fluor 647 (polyclonal) | Thermo Fisher Scientific | A21235 | (1:500) |
| Antibody | Goat anti-guinea pig Alexa Fluor 555 (polyclonal) | Thermo Fisher Scientific | A21435 | (1:500) |
| Other | Mounting medium with DAPI | Abcam | ab104139 | Mounting media used for immunofluorescence |
| Other | Alexa Fluor-488 hydrazydes | Thermo Fisher Scientific | #A10436 | 10 mM—GFP tracer used for DA neurons validation (Figure 5—figure supplement 2) |
| Other | Cholera Toxin Subunit B, Alexa Fluor 488 Conjugate | Thermo Fisher Scientific | #C34775 | Retrograde tracer used in Figures 3 and 5 and Figure 5—figure supplement 1 |
