Tag: Joseph Bruckner

Exploring the effect of bacterial signaling pathways on zebrafish neuro-immune development

Presenter: Dana Zaidan – Neuroscience

Faculty Mentor(s): Joseph Bruckner, Judith Eisen

Session: (In-Person) Poster Presentation

The gut microbiota has been linked to human health and development. We found that the gut microbiota is required for normal zebrafish social behavior, but how it influences the brain development required for social behavior is not well understood. We previously identified a population of zebrafish forebrain neurons that are also required for normal social behavior. By raising zebrafish “germ-free”, we found that the microbiota is required for normal forebrain neuronal arborization.

Microglia are brain-resident immune cells that remodel neurons and are excellent candidates for mediating interactions between the microbiota and the brain. We previously discovered that the microbiota promotes forebrain microglial abundance. We also found that neuronal arborization and microglial abundance are restored in germ-free fish after colonization with several different zebrafish-associated bacterial strains, suggesting that the microbiota might influence social neurodevelopment by a mechanism common to many bacteria. One pathway we explored involves a class of host proteins that receive bacterial signals called the Toll-like receptor (TLR) proteins. We also explored if and how proteins present in bacterial cell walls are sensed by host mechanisms in the brain. Identifying the signaling components that link the microbiota and brain development will clarify our understanding of how host-microbe interactions can influence human health.

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 .