Delayed maturation and migration of excitatory neurons in the juvenile mouse paralaminar amygdala.

The human amygdala paralaminar nucleus (PL) contains many immature excitatory neurons that undergo prolonged maturation from birth to adulthood. We describe a previously unidentified homologous PL region in mice that contains immature excitatory neurons and has previously been considered part of the amygdala intercalated cell clusters or ventral endopiriform cortex. Mouse PL neurons are born embryonically, not from postnatal neurogenesis, despite a subset retaining immature molecular and morphological features in adults. During juvenile-adolescent ages (P21-P35), the majority of PL neurons undergo molecular, structural, and physiological maturation, and a subset of excitatory PL neurons migrate into the adjacent endopiriform cortex. Alongside these changes, PL neurons develop responses to aversive and appetitive olfactory stimuli. The presence of this homologous region in both humans and mice points to the significance of this conserved mechanism of neuronal maturation and migration during adolescence, a key time period for amygdala circuit maturation and related behavioral changes.

Immature excitatory neurons in the amygdala come of age during puberty.

The human amygdala is critical for emotional learning, valence coding, and complex social interactions, all of which mature throughout childhood, puberty, and adolescence. Across these ages, the amygdala paralaminar nucleus (PL) undergoes significant structural changes including increased numbers of mature neurons. The PL contains a large population of immature excitatory neurons at birth, some of which may continue to be born from local progenitors. These progenitors disappear rapidly in infancy, but the immature neurons persist throughout childhood and adolescent ages, indicating that they develop on a protracted timeline. Many of these late-maturing neurons settle locally within the PL, though a small subset appear to migrate into neighboring amygdala subnuclei. Despite its prominent growth during postnatal life and possible contributions to multiple amygdala circuits, the function of the PL remains unknown. PL maturation occurs predominately during late childhood and into puberty when sex hormone levels change. Sex hormones can promote developmental processes such as neuron migration, dendritic outgrowth, and synaptic plasticity, which appear to be ongoing in late-maturing PL neurons. Collectively, we describe how the growth of late-maturing neurons occurs in the right time and place to be relevant for amygdala functions and neuropsychiatric conditions.