A Coming-Of-Age Story: Neuronal Circuits Controlling Behavior in Early Life
TWO-DAY LIFE SCIENCE ENGINEERING MINI-SYMPOSIUM
(talk five)
Abstract:
How does animal behavior first emerge during development? Modern studies of neuronal circuit development have largely focused on sensory systems or prenatal stages. Much less is known about postnatal changes and early life functions of brain regions dedicated to specific instinctive behaviors. To address this, we focused on the preoptic area (POA) of the hypothalamus, a brain region that governs social behaviors, such as aggression and mating, as well as homeostatic functions, such as sleep and thermoregulation (Kaplan et al., Biorxiv 2024). How POA cell types involved in these diverse functions emerge developmentally had been completely unexplored. We molecularly profiled POA cell types in mice using single-nucleus RNA-sequencing at nine ages, encompassing developmental transitions such as birth, weaning, and puberty. This revealed several novel insights. (a) Nearly all ~150 POA cell types were distinguishable as early as embryonic day 14 (E14). This is in striking contrast to cortical or sensory systems, where cell type diversification occurs over days or weeks postnatally. (b) While all cell types are diversified early, most show immature gene expression profiles, lacking neuropeptide or ion channel expression characteristic of their adult states. We found that different cell types mature along diverse timelines, in a manner partly correlated with developmental changes in the behaviors the cell types control. (c) We next asked how POA development is affected by environmental inputs, by performing snRNA-seq in five mutant lines, each impaired in a specific sensory modality crucial for POA function. This uncovered a major role for pheromonal input in POA cell type maturation: mutant animals showed a ~10-day delay in the expression of core neuronal maturation genes. This suggests a putative critical period, during which time pheromonal input is essential for proper cell type development. My work sheds light on how early life social experience may have long-term impacts on social behavior, as has been suggested through isolation experiments in primates or orphanage intervention studies in humans, and as a risk factor for autism spectrum disorder.
Bio:
Harris is currently a postdoctoral fellow in the lab of Catherine Dulac at Harvard University. He received his Bachelor’s degree in Biology from New York University in 2012. That same year, Harris moved to Vienna, Austria, where he performed his PhD work under the supervision of Manuel Zimmer at the IMP. During his PhD, Harris identified neuronal population dynamics governing locomotory behaviors in C. elegans, using a newly established brain-wide, single-cell calcium imaging approach. He then moved to Harvard in 2020, where he has established a developmental molecular atlas of the developing hypothalamic preoptic area.
Zoom link for attending remotely, if needed: https://epfl.zoom.us/j/69315453283
(talk five)
Abstract:
How does animal behavior first emerge during development? Modern studies of neuronal circuit development have largely focused on sensory systems or prenatal stages. Much less is known about postnatal changes and early life functions of brain regions dedicated to specific instinctive behaviors. To address this, we focused on the preoptic area (POA) of the hypothalamus, a brain region that governs social behaviors, such as aggression and mating, as well as homeostatic functions, such as sleep and thermoregulation (Kaplan et al., Biorxiv 2024). How POA cell types involved in these diverse functions emerge developmentally had been completely unexplored. We molecularly profiled POA cell types in mice using single-nucleus RNA-sequencing at nine ages, encompassing developmental transitions such as birth, weaning, and puberty. This revealed several novel insights. (a) Nearly all ~150 POA cell types were distinguishable as early as embryonic day 14 (E14). This is in striking contrast to cortical or sensory systems, where cell type diversification occurs over days or weeks postnatally. (b) While all cell types are diversified early, most show immature gene expression profiles, lacking neuropeptide or ion channel expression characteristic of their adult states. We found that different cell types mature along diverse timelines, in a manner partly correlated with developmental changes in the behaviors the cell types control. (c) We next asked how POA development is affected by environmental inputs, by performing snRNA-seq in five mutant lines, each impaired in a specific sensory modality crucial for POA function. This uncovered a major role for pheromonal input in POA cell type maturation: mutant animals showed a ~10-day delay in the expression of core neuronal maturation genes. This suggests a putative critical period, during which time pheromonal input is essential for proper cell type development. My work sheds light on how early life social experience may have long-term impacts on social behavior, as has been suggested through isolation experiments in primates or orphanage intervention studies in humans, and as a risk factor for autism spectrum disorder.
Bio:
Harris is currently a postdoctoral fellow in the lab of Catherine Dulac at Harvard University. He received his Bachelor’s degree in Biology from New York University in 2012. That same year, Harris moved to Vienna, Austria, where he performed his PhD work under the supervision of Manuel Zimmer at the IMP. During his PhD, Harris identified neuronal population dynamics governing locomotory behaviors in C. elegans, using a newly established brain-wide, single-cell calcium imaging approach. He then moved to Harvard in 2020, where he has established a developmental molecular atlas of the developing hypothalamic preoptic area.
Zoom link for attending remotely, if needed: https://epfl.zoom.us/j/69315453283
Practical information
- Informed public
- Free
Organizer
- Prof. Felix Naef, & Prof. Matteo Dal Peraro, School of Life Sciences, EPFL
Contact
- Institute of Bioengineering (IBI), Dietrich REINHARD