Loss of Intercalated Cells (ITCs) in the Mouse Amygdala ofTshz1Mutants Correlates with Fear, Depression, and Social Interaction Phenotypes

• DOI: 10.1523/jneurosci.1412-17.2017
• Publication Date: 2017-12-18T18:30:24Z
• Authors: Jeffrey Kuerbitz; Melinda Arnett; Sarah Ehrman; Michael T. Williams; Charles V. Vorhees; Simon E. Fisher; Alistair N. Garratt; Louis J. Muglia; Ronald R. Waclaw; Kenneth Campbell
• Keywords: Ganglionic eminence; Ectopic expression

The intercalated cells (ITCs) of the amygdala have been shown to be critical regulatory components amygdalar circuits, which control appropriate fear responses. Despite this, molecular processes guiding ITC development remain poorly understood. Here we establish zinc finger transcription factor Tshz1 as a marker ITCs during their migration from dorsal lateral ganglionic eminence through maturity. Using germline and conditional knock-out (cKO) mouse models, show that is required for proper differentiation ITCs. In absence , migrating precursors fail settle in stereotypical locations encapsulating BLA. Furthermore, they display reductions Foxp2 ectopic persistence Sp8. mutant increased cell death at postnatal time points, leading dramatic reduction by 3 weeks age. line with -null mutants also loss suggesting may function downstream maintenance Behavioral analysis male cKOs revealed defects extinction well an increase floating forced swim test, indicative depression-like phenotype. Moreover, significantly impaired social interaction (i.e., passivity) regardless partner genetics. Together, these results suggest plays role fear, behavioral deficits arise absence. SIGNIFICANCE STATEMENT We here expressed within amygdala. These neurons previously play crucial extinction. exhibit severely reduced numbers result abnormal migration, differentiation, survival neurons. correlates appearance behaviors reminiscent depressive disorders observed human patients distal 18q deletions, including locus.