A prefrontal–paraventricular thalamus circuit requires juvenile social experience to regulate adult sociability in mice
Authors: Scott J Russo
Schahram Akbarian
Yury Garkun
Lucy K Bicks
Meghan E Flanigan
Keaven Caro
Susanna Im
Kazuhiko Yamamuro
Kevin J Norman
Daisuke Kato
Klas Kullander
Hirofumi Morishita
Michael B Leventhal
Masato Sadahiro
Journal: Nature Neuroscience (2020)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Juvenile social isolation; sociability deficits; neural circuit mechanisms; medial prefrontal cortex; posterior paraventricular thalamus
Affiliations: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, NY, USA., Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, NY, USA., Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, New York, NY, USA., Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York, NY, USA., Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, NY, USA., Department of Psychiatry, Nara Medical University, Kashihara, Nara, Japan., Unit of Developmental Genetics, Department of Neuroscience, Uppsala University, Uppsala, Sweden., Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, NY, USA. ., Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, NY, USA. ., Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, New York, NY, USA. ., Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York, NY, USA. ., Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, NY, USA. .

Abstract:  Juvenile social isolation reduces sociability in adulthood, but the underlying neural circuit mechanisms are poorly understood. We found that, in male mice, 2 weeks of social isolation immediately following weaning leads to a failure to activate medial prefrontal cortex neurons projecting to the posterior paraventricular thalamus (mPFC→pPVT) during social exposure in adulthood. Chemogenetic or optogenetic suppression of mPFC→pPVT activity in adulthood was sufficient to induce sociability deficits without affecting anxiety-related behaviors or preference toward rewarding food. Juvenile isolation led to both reduced excitability of mPFC→pPVT neurons and increased inhibitory input drive from low-threshold-spiking somatostatin interneurons in adulthood, suggesting a circuit mechanism underlying sociability deficits. Chemogenetic or optogenetic stimulation of mPFC→pPVT neurons in adulthood could rescue the sociability deficits caused by juvenile isolation. Our study identifies a pair of specific medial prefrontal cortex excitatory and inhibitory neuron populations required for sociability that are profoundly affected by juvenile social experience. 

Retracted: No

PubPeer comments:
 Could the authors examine Figure 1b and offer an explanation for what appears to be a horizontal splice in the representative image? One reader on social media suggests this is a mosaic. *** Enhanced brightness ![file] *** Original ![file] *** Full figure and caption ![file] ,