The neuron-specific transcription factor T-box brain 1 (TBR1) regulates brain 
development. Disruptive mutations in the TBR1 gene have been repeatedly 
identified in patients with autism spectrum disorders (ASDs). Here, we show that 
Tbr1 haploinsufficiency results in defective axonal projections of amygdalar 
neurons and the impairment of social interaction, ultrasonic vocalization, 
associative memory and cognitive flexibility in mice. Loss of a copy of the Tbr1 
gene altered the expression of Ntng1, Cntn2 and Cdh8 and reduced both inter- and 
intra-amygdalar connections. These developmental defects likely impair neuronal 
activation upon behavioral stimulation, which is indicated by fewer 
c-FOS-positive neurons and lack of GRIN2B induction in Tbr1(+/-) amygdalae. We 
also show that upregulation of amygdalar neuronal activity by local infusion of 
a partial NMDA receptor agonist, d-cycloserine, ameliorates the behavioral 
defects of Tbr1(+/-) mice. Our study suggests that TBR1 is important in the 
regulation of amygdalar axonal connections and cognition.