Archival ReportIdentification of a Corticohabenular Circuit Regulating Socially Directed Behavior
Section snippets
Methods and Materials
Detailed protocols can be found in the Supplement.
Global Functional MRI Signature Associated With Social Dysfunction
To screen for global activity changes associated with PFC hyperactivity and social dysfunction, we took advantage of DREADDs 16, 17, 18. DREADDs are engineered G protein–coupled receptors designed to respond to an otherwise biologically inert ligand. To increase excitation in the PFC, we transduced PFC pyramidal neurons (Emx-positive) with the excitatory DREADD hM3Dq. Using multielectrode arrays, we confirmed that DREADDs led to a persistent and strong increase in neuronal activity. Brain
Discussion
Perturbed circuit homeostasis in the PFC has been proposed as a common neural substrate of social impairments seen in ASD and schizophrenia. Rodent optogenetic studies have shown that the PFC governs social behavior via top-down control over the activity dynamics of the midbrain reward system 31, 32. However, the neural pathways that connect the PFC to the social reward pathways have not yet been delineated. Here we screened for PFC circuit partners involved in the control of social behavior
Acknowledgments and Disclosures
This work is partially supported by the Gatsby Charitable Trust (AG) and by the postdoctoral program at F. Hoffman–La Roche (MB, TJS).
We thank Bryan L. Roth for the DREADD constructs. We thank Claire Coulon-Bainier for help with surgical procedures and thank Stephanie Schoeppenthau, Sebastian Debilly, and Ciril Marius Waelti for technical assistance with the fMRI experiments. We thank Roger Redondo for help with the in vivo optogenetic experiments. We also thank Laurence Ozmen, Marie-Therese
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AG is currently affiliated with Research and Early Development, Biogen, Cambridge, Massachusetts.