Characterization of cell-type specific IRSp53 mutant mice

Abstract

IRSp53 as an actin modulator is critical for growth and maintenance of dendritic spine, and its knockout in mice showed social deficit. Social deficit makes great burden to psychiatric patients such as schizophrenia and autism. But still, it is needed to be investigated its beneath mechanism and effective therapy for social deficit. Here I show telencephalic excitatory neuron specific Emx1-Cre

IRSp53 flox/flox (f/f) conditional knockout (cKO) mice have social deficit. Chemogenetic modulation of LH restores social deficit in Emx1-Cre

IRSp53 f/f cKO mice, butaggravates social deficit in f/f mice. In addition, I measure inhibitory/excitatory (I/E) ratio from optogenetically evoked synaptic transmission on neurons of the ventral tegmental area (VTA). It is presented with increasing I/E ratio with Emx1-Cre

IRSp53 f/f cKO mice and decreasing I/E ratio with f/f mice during chemogenetic modulation, respectively. Furthermore, inhibitory neuron specific chemogenetic modulation in LH makes social behavior increase in both Emx1-Cre

IRSp53 f/f cKO and control mice. This is the first study to utilise the circuit between LH and VTA for rescue of social behavior in disease-model mouse. In addition, this finding has clinical implication to treat social deficit in psychiatric patients.