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Updated: Dec 10, 2025
Author Spotlight: Understanding Adolescent Social Adversity Effects on Neurodevelopment in Mice
Published on: March 15, 2024
A prefrontal-paraventricular thalamus circuit requires juvenile social experience to regulate adult sociability in
Kazuhiko Yamamuro1,2,3,4,5,6, Lucy K Bicks1,2,3,4,5, Michael B Leventhal1,2,3,4,5
1Department of Psychiatry, 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.
Insights
Juvenile social isolation impairs adult sociability by disrupting medial prefrontal cortex (mPFC) neuron pathways. Restoring mPFC neuron activity can reverse these social deficits.
Area of Science:
- Neuroscience
- Behavioral Science
- Developmental Psychology
Background:
- Juvenile social isolation is known to reduce adult sociability.
- The specific neural circuits and mechanisms underlying this effect remain largely unknown.
Purpose of the Study:
- To investigate the neural circuit mechanisms by which early-life social isolation affects adult sociability.
- To identify specific neuronal populations in the medial prefrontal cortex (mPFC) involved in social behavior.
Main Methods:
- Utilized chemogenetics and optogenetics in male mice to manipulate neuronal activity.
- Examined the medial prefrontal cortex to posterior paraventricular thalamus (mPFC→pPVT) pathway.
- Assessed sociability, anxiety-related behaviors, and reward-seeking behaviors.
Main Results:
- Juvenile isolation impaired the activation of mPFC→pPVT neurons during social interaction in adulthood.
- Suppression of mPFC→pPVT activity induced sociability deficits.
- Isolation reduced mPFC→pPVT neuron excitability and increased inhibitory input from somatostatin interneurons.
- Stimulation of mPFC→pPVT neurons rescued isolation-induced sociability deficits.
Conclusions:
- Specific excitatory and inhibitory neuron populations in the mPFC are critical for sociability.
- Juvenile social experiences significantly impact these mPFC circuits, affecting adult social behavior.
- The mPFC→pPVT pathway is a key circuit mediating the effects of early social isolation on adult sociability.
