Tail of the striatum and regulation of exploratory behavior in a wild mouse

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Summary Adolescence is a time of both vulnerability and opportunity for brain and behavioral development. Cortical spine pruning and outgrowth of the axons of the dopamine system are two hallmarks of adolescent brain development that can be observed in humans, primates, and rodents (Delevich et al. 2021). Exploration, risk taking, and dispersal from the natal site or familial group are core behavioral milestones of adolescent development in many species, yet we currently do not understand how and why these behaviors are regulated by changes in neurobiology (Lin & Wilbrecht, 2022). The relationship between these topics is challenging to study because programs for adolescent development are likely disrupted by domestication in lab animals. A wild species of mouse, Mus spicilegus, presents an exciting model in which to study adolescent development and risk taking because it shows different life history trajectory depending on season of birth. M. spicilegus born in spring and summer on long days (LD) disperse in the first three months of life, while M. spicilegus born on shorter autumnal days (SD) delay dispersal through the wintertime. We are breeding these mice in a laboratory context to compare age-matched mice who will express adolescent developmental programs on different timelines. In preliminary data we confirmed that when we reared M. spicilegus on an SD 10h:14h light:dark photoperiod, they showed reduced weight gain and reduced novel object investigation compared to 12h:12h reared mice (Cryns et al., 2022). Here we will test the idea that differences in photoperiod alter risk taking exploratory behavior in M. spicilegus via effects on the development of the tail of the striatum (TS). We have decided to focus on the TS area because of recent work showing that dopamine release in the TS regulates approach and retreat behavior in the context of a novel object (Menegas et al., 2018; Akiti et al., 2022). This makes it an exciting candidate for the control of a larger repertoire of bold adolescent exploratory behaviors that support natal dispersal. In Aim 1, we will use newly established nIRCat imaging in ex vivo slices (Beyene et al., 2019) and fiber photometry in vivo recording of dLight to test how rearing in short day (SD) and long day (LD) photoperiod impacts dopamine release in the tail of the striatum. In Aim 2, we will test how rearing in short day (SD) and long day (LD) photoperiod impacts spine pruning on the cortical neurons that project to the tail of the striatum. Photoperiod manipulation will create new contrasts that allow us to dissociate age from function. These data will be impactful because they will help to isolate mechanisms that evolved to regulate adolescent risk-taking and dispersal related behavior. These data can have broad impact on understanding vulnerabilities and opportunities in human adolescence.