Modulation of prefrontal cortex excitation/inhibition balance rescues social behavior in CNTNAP2 -deficient mice

• DOI: 10.1126/scitranslmed.aah6733
• Publication Date: 2017-08-02T18:10:20Z
• Authors: Aslihan Selimbeyoglu; Christina K. Kim; Masatoshi Inoue; Soo Yeun Lee; Alice S. O. Hong; Isaac Kauvar; Charu Ramakrishnan; Lief E. Fenno; Thomas J. Davidson; Matthew Wright; Karl Deisseroth
• Keywords: Knockout mouse; Conditional gene knockout

Alterations in the balance between neuronal excitation and inhibition (E:I balance) have been implicated neural circuit activity-based processes that contribute to autism phenotypes. We investigated whether acutely reducing E:I mouse brain could correct deficits social behavior. used mice lacking CNTNAP2 gene, which has autism, achieved a temporally precise reduction medial prefrontal cortex (mPFC) either by optogenetically increasing excitability of inhibitory parvalbumin (PV) neurons or decreasing excitatory pyramidal neurons. Surprisingly, both these distinct, real-time, reversible optogenetic modulations rescued behavior hyperactivity adult Using fiber photometry, we discovered native mPFC PV activity differed knockout wild-type mice. During interactions with other mice, neuron increased compared novel object, whereas this difference was not observed Together, results suggest real-time modulation can rescue reminiscent