Understanding microbial modulation of neuronal morphology in zebrafish

Presenter(s): Max Grice—Computer Science

Faculty Mentor(s): Judith Eisen, Joseph Bruckner

Session 4: Earning your Stripes

Increasing evidence supports a role for the intestinal microbiota in modulating host neurodevelopment and behavior, including complex social behaviors . Recent research has also linked the microbiota to neurological disorders including autism spectrum disorder (ASD), depression, Alzheimer’s Disease, and Parkinson’s Disease . However, the mechanisms of these interactions between the host-associated microbiota and neurodevelopment remain unclear . Using zebrafish raised in the absence of the microbiota, or germ-free (GF), our group has found that the microbiota modulates zebrafish social behavior . Normal social behavior requires neurons in a region of the brain called the ventral telencephalon (vTel) . Therefore, we hypothesized that the microbiota may modulate social behavior by altering development of vTel neurons, resulting in changes in vTel neuron morphology . To measure morphology of vTel neurons, we combined sparse mosaic labelling and high- resolution confocal microscopy to image individual vTel neurons . We used Imaris software to segment individual neurons and extract morphological measurements and adapted several software packages to warp and register individual neurons to an average reference brain in each condition . We found that vTel neurons from GF fish are significantly more complex than vTel neurons from their conventionally raised siblings . Together, this work suggests that the microbiota may modulate social behavior by restraining complexity of ventral forebrain neurons . Understanding the specific mechanism through which the microbiota normally modulates social behavior will allow us to better understand microbial modulation of neurodevelopment and therefore construct more effective treatments for neurological disorders that may result from dysbiosis of the host-associated microbiota .

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