The broad interest of 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 sensorimotor functions in the brain. These investigators are crucial to understand how organisms respond to the environment with the appropriate responses. We utilize diverse techniques to dissect molecular and circuit functions in the brain including: molecular genetic techniques, CRISPR, functional imaging, next-gen sequencing and behavioral analysis.
Two current areas of investigation:
1. Circuit and molecular mechanisms of sensory-dependent plasticity:
During early development, restricted developmental windows known as critical periods exhibit heightened plasticity and responsiveness to sensory input. Sensory input during critical periods refines sensory processing, and disruptions can lead to sustained defects associated with numerous neuropsychiatric disorders. Recently, subcortical modulation of critical periods has been described, challenging decades of cortex-centric dogma. We developed a zebrafish model of visual critical period plasticity providing a unique sub-cortical model to describe neuron-level mechanisms of sensory-dependent plasticity. We will leverage this model to identify how sensory-input modulates circuit and molecular mechanisms to regulate critical periods and neural plasticity.
2. Understanding how hemispheric differences in the brain modulate behavior:
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.
3D rendering of a unilateral set of neurons and projections that partially establish a necessary circuit for intrinsic motor bias in larval zebrafish.