Kevin Mastro

Adolescence, the transition from juvenile to adulthood, is a developmental period marked by a prolonged structural change in brain circuits that coincides with an increase in cognitive capacity, sensory seeking and risk-seeking behaviors. From humans to monkeys to rodents, there is evidence for a profound change across the adolescence window in prefrontal cortical structure, connectivity, and function. While inroads have been made to understand the developmental mechanisms that drive PFC maturation and how the PFC contributes to an array of cognitive tasks, the connection between the PFC's developmental changes and its impact on behavior remain unclear. Utilizing behavior, physiology and cognitive modeling, we will delineate the strategies and computations underlying risk-seeking behavior across developmental ages (adolescents vs adults), sex (male vs female) and species (mouse vs non-human primate, marmoset).

Yvanka de Soysa

Yvanka's postdoctoral work focuses on dissecting the regulation and function of a developmental microglial state that we call Axon Tract Microglia (ATM). This enigmatic state appears in the white matter tracts of the corpus callosum and cerebellum in just the first week of postnatal life in mice. Due to their unique spatiotemporally distinct window of emergence, ATM are a powerful in vivo model to interrogate how the intersection of developmental origin, intrinsic gene regulatory programs and local environmental cues regulates microglial state dynamics. One goal of her work is to understand how these factors contribute to ATM state identity. The white matter tracts, where ATM reside during their brief window of emergence, comprise millions of axons that transmit and coordinate signals between brain regions. These critical communication channels are commonly disrupted in neurodevelopmental disorders, such as autism spectrum disorder. The timing of ATM emergence in white matter tracts coincides with important developmental milestones of these structures, therefore a second goal of this work is to define the functional contributions of ATM to white matter tract development and determine whether ATM dysregulation contributes to neurodevelopmental disease.

Alec Walker and Helena Barr

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It is increasingly recognized that neuroimmune communication in the central nervous system (CNS) influences brain development, homeostasis, and disease. Recent studies have revealed a diverse compartment of immune cells that reside in the choroid plexus, perivascular space, and meninges that compose the brain’s borders in the adult and degenerating brain. However, much less is known about how the brain border immune compartment develops. Through a combination of single cell RNA sequencing, flow cytometry, and imaging, we have generated and spatiotemporal map of immune cells at the borders of the brain and the stromal compartment that supports them, leading to several surprising observations indicating that the meninges composes a unique immune niche in early life. Further, how immune cells at the brain’s borders sense and appropriately respond to signals  from healthy developing and adult CNS is poorly understood. One hypothesis is that brain border immune cells interface with the brain’s drainage system (e.g. glymphatic/lymphatic systems) to sample material that is draining from the brain parenchyma. We have identified transcriptionally distinct populations of brain border associated macrophages (BAMs) at different brain border interfaces that sample material draining from the brain and have developed transgenic tools to probe their potential roles in facilitating waste clearance from the brain and regulating brain-specific immunity in different disease contexts. Overall, we aim to build a more comprehensive picture of how neuroimmune signaling at the borders of the brain shapes healthy brain development and/or generation of immune privilege characteristic of the CNS.