In nearly all bilateral organisms significant left/right asymmetries, in both activity and structure, are observed in the central nervous system. Similarly, intrinsic behavioral asymmetries are observed throughout vertebrates and invertebrates; behaviors comparable to human handedness. These intrinsic behavioral biases represent a salient form of individual variation, which impacts how organisms interacts with nearly all features of their environment and populations evolution in ever changing environments. However, the molecular cues and neural substrates that establish functional left/right asymmetries in the brain are very poorly understood. This gap in knowledge is significant as a growing body of evidence demonstrates that the strength of lateralization within specific brain regions can correlate to performance efficiency and in humans, brain asymmetries are dramatically reduced in numerous neuropsychiatric disorders. Understanding how left/right patterning occurs in the brain is a fundamental component in elucidating the basis of individual variability, behavioral performance, and neuropsychiatric pathogenesis.
A primary goalof the Horstick lab is to capitalize on the strengths of the zebrafish model system to elucidate the molecular cues and the neural framework that establishes functional lateralization in the brain. Zebrafish larvae show a durable sensory driven locomotor bias throughout larval development (Horstick et al, 2020. Natcom). By leveraging this robust model my lab will utilize molecular genetic techniques, imaging, next-gen sequencing and behavioral analysis to discover specific neural substrates and molecular signaling pathways necessary for the development and implementation of laterality in brain function. This information will significantly advance our understanding of how left/right asymmetries in the brain impact behavior and disease states.
Other areas of interest are the development of new genetic techniques for neural imaging and mapping, identifying molecular mechanisms of neuromuscular diseases and state-dependent modulation of behavioral responsiveness.
3D rendering of a unilateral set of neurons and projections that partially establish a necessary circuit for intrinsic motor bias in larval zebrafish.