Functional maturation of amygdala circuitry during adolescence

PROJECT SUMMARY/ABSTRACT The transition from adolescence to adulthood is a critical period of development characterized by significant changes in social-emotional behavior. One of the central brain structures modulating this transition is the amygdala. The development of the amygdala continues through adolescence, undergoing an expansion in size and neuron number into early adulthood. These changes enable healthy social and emotional development, and perturbations in amygdala development and maturation are linked a host of mental health disorders, most notably autism spectrum disorders (ASD). However, the amygdala neuronal and circuit substrates underlying changes coincident with this major life transition remain little understood. In our published studies in humans, and our unpublished work in mice, we identified and characterized a unique population of immature neurons in the paralaminar nucleus of the amygdala (PL). While these neurons are born embryonically, they interestingly delay their maturation until adolescence when they differentiate into excitatory neurons. Thus, the PL is well positioned to play a key role in the behavioral changes that are associated with the transition from adolescence to maturity. The goal of our proposed studies is to understand the role of amygdala late-maturing neurons in the circuitry, neuronal responsivity and behavioral transition that occurs during adolescence. To test this, we will examine the dynamic circuit changes in input connectivity (Aim 1), neuronal responsiveness (Aim 2), and the role the PL plays in the behavioral transition (Aim 3) from adolescence to early adulthood. Our discovery and characterization of PL neurons that undergo maturation coincident with adolescence suggests a novel mechanism of brain plasticity during a critical stage of post natal development. Our proposed studies are also an essential step to understanding the role late maturing PL neurons play in neuro-atypical brain function associated with disorders of social cognition such as ASD and the long-term consequences of early life stress.