Early life stress (ELS) in the form of child abuse/neglect is associated with an increased risk of developing social dysfunction in adulthood. Little is known, however, about the neural substrates or the neuromodulatory signaling that govern ELS-induced social dysfunction. Here, we show that ELS-induced downregulation of dopamine receptor 3 (Drd3) signaling and its corresponding effects on neural activity in the lateral septum (LS) are both necessary and sufficient to cause social abnormalities in adulthood. Using in vivo Ca2+ imaging, we found that Drd3-expressing-LS (Drd3LS) neurons in animals exposed to ELS show blunted activity in response to social stimuli. In addition, optogenetic activation of Drd3LS neurons rescues ELS-induced social impairments. Furthermore, pharmacological treatment with a Drd3 agonist, which increases Drd3LS neuronal activity, normalizes the social dysfunctions of ELS mice. Thus, we identify Drd3 in the LS as a critical mediator and potential therapeutic target for the social abnormalities caused by ELS.
Pubmed ID: 29276054 RIS Download
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View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
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View all literature mentionsMus musculus with name C57BL/6J from IMSR.
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Mus musculus with name BTBR T+ Itpr3
Mus musculus with name B6.Cg-Gt(ROSA)26Sortm6(CAG-ZsGreen1)Hze/J from IMSR.
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Mus musculus with name BTBR T+ Itpr3
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View all literature mentionsMus musculus with name B6.Cg-Gt(ROSA)26Sortm6(CAG-ZsGreen1)Hze/J from IMSR.
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