Dynamic encoding of social threat and spatial context in the hypothalamus
- Epigenetics & Neurobiology Unit, EMBL Rome, European Molecular Biology Laboratory, Italy
- EMBL and Heidelberg University, Faculty of Biosciences, Germany
- Masters Course in Biomedical Engineering, Faculty of Civil and Industrial Engineering, Sapienza University, Italy
Figures
Figure 1 with 2 supplements
VMHvl encodes social threat.
(a–d) Microendoscopy was used to image single unit calcium activity in VMHvl neurons of awake behaving mice expressing GCaMP6s. (c) Representative processed endoscope image used to extract relative …
Figure 1—figure supplement 1
Complete behavioral paradigms.
Graphic depicting complete behavioral paradigm in (a) forward and (b) reverse order. (c) Aggression behavioral paradigm On the aggression day a BALB/c intruder was introduced into closed home …
Figure 1—figure supplement 2
Spatial filter maps from all days of calcium imaging.
(a) Spatial filter maps from all the recording days for defeat-first group. (b) Spatial filter maps from all the recording days for reverse group. (c) Overlap between filters from first and last day …
Figure 2 with 3 supplements
Dynamic encoding of spatial context in VMHvl.
(a) In vivo calcium endoscopy was carried out in mice subjected to (left, middle) social defeat and then exposed again to (right) the defeat context one day later. (b, e) Activity traces of …
Figure 2—figure supplement 1
Overlap between social neurons.
Venn diagrams showing overlap between: (a) Social+, home+ and far-chamber+ neurons, (b) Social-, home+ and far-chamber+ neurons, (c) Social+, social- and defense+ neurons.
Figure 2—figure supplement 2
Representation of territory before and after defeat for all mice.
(a–b) LDA plots of neuron ensemble activity for all mice in the home, far chamber, or corridor (a) before defeat (b) after defeat. Note that data for the first mouse in panel a and b is the same as …
Figure 2—figure supplement 3
Comparison of time spent in different chambers during memory day.
(a) Plot showing time spent in different chambers by defeat-first group on both context days. (b) Plot showing time spent in different chambers by reverse group on both context days. (c) Plot …
Figure 3
Overlapping encoding of social defense and aggression.
(a–c) Representative images of cFos-tagged (red) and cFos-immunolabeled (green), and double labelled (yellow) cells in brain sections from mice subjected sequentially to social defeat and aggression …
Figure 4 with 3 supplements
Social defeat remodels VMHvl activity.
(a) LDA plot of neuron ensemble activity for a representative mouse during repeated defeat and aggression episodes. Each data point represents a frame of calcium imaging data projected onto the …
Figure 4—figure supplement 1
Comparison of behavior between days and groups.
(a) Plots showing time spend defending and in upright position for all mice during defense days 1 and 2 (p>0.05) revealing no difference between the days. (b) Plot showing comparison of defense time …
Figure 4—figure supplement 2
Representation of defeat and aggression states in LD space for all mice.
(a–b) LDA plots of neuron ensemble activity for all mice during repeated defeat and aggression episodes in (a) forward order and (b) reverse order of behavior. Inset indicates order of defeat and …
Figure 4—figure supplement 3
Representation of defeat day 1 and defeat day 2 in LD space for all mice and esr1+ mice.
LDA plots of neuron ensemble activity for all mice during sequential defeat episodes. Each data point represents a frame of calcium imaging data projected onto the first linear discriminant (a) forwa…
Figure 5
Social defeat remodels VMHvl function.
(a–b) Optogenetic stimulation of Esr1+ neurons following local delivery of AAV-Ef1a::FLEX-ChR2-eYFP into the VMHvl of Esr1::Cre mice. (c) Mice were stimulated intermittently (20 Hz, 20 ms pulse, 30 …
Videos
Video 1
Assessment+ cell close to stimulus.
Video 2
Assessment+ cell far from stimulus.
Video 3
Post-defeat optogenetic activation of Esr1+ neurons in VMHvl.
Tables
Key resources table
| Reagent type (species) or resource | Designation | Source or reference | Identifiers | Additional information |
|---|---|---|---|---|
| Strain, strain background (M. musculus) | C57BL/6J | Charles River | RRID:IMSR_JAX:000664 | |
| Strain, strain background (M. musculus) | CD-1 | Charles River | RRID:IMSR_CRL:022 | |
| Strain, strain background (M. musculus) | BALB/c | EMBL | Internal mouse colony at EMBL Rome | |
| Genetic reagent (M. musculus) male | Esr1:Cre | Jackson Laboratory | RRID:IMSR_JAX:017913 | |
| Genetic reagent (M. musculus) male | cFos::CreERT2 | Jackson Laboratory | RRID:IMSR_JAX:021882 | |
| Genetic reagent (M. musculus) male | RC::LSL-tdTomato | Jackson Laboratory | RRID:IMSR_JAX:007914 | |
| Antibody | goat polyclonal anti-cFos SC-52G | Santa Cruz | RRID:AB_2629503 | |
| Chemical compound, drug | 4-hydroxytamoxifen 70% z-isomer | Sigma | H6278 CAS: 68392-35-8 | |
| Strain, strain background (M. musculus) | AAV-EF1a-DIO-hChR2(E123T/T159C)-EYFP | UNC Vector Core | ||
| Strain, strain background (M. musculus) | AAV-EF1a-DIO-EYFP | UNC Vector Core | ||
| Strain, strain background (M. musculus) | AAV5-CAG::Flex-GCaMP6s | Penn Vector Core | ||
| Strain, strain background (M. musculus) | AAV5-hSyn::GCaMP6s | Penn Vector Core | ||
| Software, algorithm | ImageJ | https://imagej.nih.gov/ij/ | RRID:SCR_003070 | |
| Software, algorithm | TurboReg | http://bigwww.epfl.ch/thevenaz/turboreg/ | RRID:SCR_014308 | Thevenaz et al., 1998 |
| Software, algorithm | Observer XT11 | Noldus | https://www.noldus.com/observer-xt-animal | |
| Software, algorithm | Prism 5 | Graphad | RRID:SCR_002798 | https://www.graphpad.com |
| Software, algorithm | V2.2 Radiant | Plexon | https://plexon.com/products/plexbright-4-channel-optogenetic-controller-radiant-v2/ | |
| Software, algorithm | Salomon Coder | https://solomon.andraspeter.com/ | Behaviour coding software | |
| Software, algorithm | scikit-learn | https://scikit-learn.org | RRID:SCR_002577 | Pedregosa et al., 2012 |
Additional files
-
Supplementary file 1
Table showing number of ROIs for each mouse that were assessed for the indicated behavior.
Territory includes both Home and Far chamber cells.
- https://cdn.elifesciences.org/articles/57148/elife-57148-supp1-v1.docx
-
Transparent reporting form
- https://cdn.elifesciences.org/articles/57148/elife-57148-transrepform-v1.pdf
