Function of the paralaminar amygdala from adolescence to adulthood

About This Grant

PROJECT SUMMARY/ABSTRACT The transition from adolescence to adulthood is a critical stage 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) and the long-term behavioral consequences as a result of early life stress (ELS). 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 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, our discovery and characterization of PL neurons that undergo maturation coincident with adolescence revealed a novel mechanism of brain plasticity during a critical stage of post-natal development. Using the mouse as a model, the goal of our proposed studies is to understand the function of amygdala late-maturing neurons from adolescence to early adulthood and what drives their maturation. To test this, we will examine how PL neuronal responses change over time (Aim 1), the necessity and sufficiency of PL neurons in this transition (Aim 2), and the role inhibitory neurotransmission plays in their maturation and later function (Aim 3). 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 to which the PL has previously been linked, such as ASD and the long-term consequences of ELS.