Placement and functional properties of synaptic contacts between neurons underlie all neural computations, from sensory perceptions to abstract thought and behavioral output. Mismatch in connectivity causes alterations in activity of neural circuits that are at the core of multiple neurological and psychiatric disorders. Although developmental steps leading to emergence of the mature cerebellar morphology, cytoarchitecture, and microcircuitry have been meticulously characterized, molecular mechanisms that orchestrate maturation of cerebellar circuits are much less understood. We strive to gain mechanistic understanding of the molecular signals regulating cellular behaviors that culminate in synaptic matchmaking and refinement, ultimately leading to the exquisite specificity of synaptic connectivity. Specifically, we focus on the role of cannabinoid signaling in directing development and function of cerebellar circuits, and in adjustment of cerebellum-modified behaviors. Questions under active investigation include:
- How do endogenous cannabinoids regulate cerebellar wiring?
- What are the molecular mechanisms of cell-type specific effects of cannabinoid signaling?
- Are exogenous cannabinoids teratogenic during cerebellar development?
- What are the structural, functional, and behavioral consequences of retrograde cannabinoid signaling in inhibitory cerebellar synapses?
We approach these questions experimentally in-vivo and in-vitro:
- Morphological, anatomical, histological and cytochemical analysis in conventional and conditional mouse mutants
- Axon tracing, analysis of neuron morphology, 3D reconstruction
- Immunohistochemistry, confocal microscopy
- Primary explant and dissociated neuronal cultures
- Mouse behavior