Our goal is to promote the healthy transition to adulthood and mitigate the risk or severity of psychiatric disease and substance use disorders.

We aim to identify key cell types and neural circuits that undergo changes in structure and function during adolescence, determine whether these processes differ in males and females, and reveal how changes in neural circuits relate to behaviors that are relevant to core symptoms of psychiatric disease and substance use disorder, and decision-making more broadly. Understanding how puberty may differentially impact the maturation of key neural circuits in males and females will be important to understanding the etiology of diseases that emerge during adolescence, including anxiety-related and psychotic disorders, as well as disorders whose trajectories are positively modified over adolescence, like Tourette’s syndrome.

Approaches

We apply a variety of approaches to examine neural structure and function in a cell type and projection-specific manner across development. Techniques include slice electrophysiology (including optogenetic circuit dissection), viral tracing, confocal microscopy, near infrared catecholamine sensor (nIRCat) imaging, and in vivo fiber photometry.

To examine the influence of puberty on brain maturation, we perform surgical and hormonal manipulations. Finally, we combine in vivo manipulation experiments (e.g. chemogenetics) and computational modeling to better understand the processes underlying behavior.

Research questions

  1. How does puberty influence synaptic pruning in the frontal cortex? Is this process cell type-specific and/or sex-dependent?

  2. How does puberty influence the maturation of inhibitory circuits, particularly those that involve fast-spiking parvalbumin+ interneurons?

  3. How does presynaptic regulation of dopamine release change across adolescence? Do these alterations occur in a sex-, puberty-, and striatal subregion-dependent manner?

Highlighted research projects

 
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Figure adapted from Beyene et al. 2019

Figure adapted from Beyene et al. 2019

Pubertal influence on feedforward inhibition in corticostriatal circuits: implications for adolescent tic remittance

Tourette syndrome (TS) symptom severity fluctuates across development, typically improving during adolescence. It has been hypothesized that the maturation of neural circuits involved in self-regulation may account for symptom improvement during adolescence, a period of dynamic brain reorganization that begins with puberty. Using mouse models, we will determine whether self-regulatory behavior improves during adolescence, whether behavioral improvement is related to functional changes in frontal cortex to striatum circuits, and whether self-regulatory behavior and circuit function are influenced by pubertal hormones. By understanding the developmental mechanisms that contribute to enhanced self-regulation we hope to uncover potential therapeutic targets for TS.

Sex and developmental differences in presynaptic modulation of dopamine release by antipsychotics

Understanding developmental changes in dopamine release and its regulation by D2 autoreceptors will be key to identifying pathophysiological mechanisms that contribute to DA dysregulation in schizophrenia (SCZ) and the prodrome. Our proposed experiments also causally test the influence of the pubertal rise in gonadal hormones on regulation of presynaptic DA release. These findings will be important for understanding the onset of SCZ during adolescence and its male bias. We plan to use novel near infrared fluorescent catecholamine nanosensors that permit exceptionally high spatial resolution for capturing DA release and reuptake/clearance dynamics in striatal tissue. The ability to measure dopamine dynamics at high spatial resolution will enable new insights into the regulation of DA release and reuptake at the level of individual release sites.