Our laboratory is interested in molecular machines that control neurotransmitter and neuromodulator signaling in the vertebrate brain, and we study how these mechanisms control microcircuit function.
Key questions
What are the transport, capture and assembly mechanisms of the presynaptic molecular machines that control exocytosis?
What are the molecular mechanisms for the control of the speed, diversity and regulation of presynaptic exocytosis?
What are the release mechanisms of neuromodulatory substances?
What is the organization of signaling structures for neuromodulators, for example the relative positioning of release and receptors?
What are the regulatory mechanisms that control neuromodulator signaling?
Active zone assembly
While the past decades have revealed many fascinating molecular mechanisms that underlie active zone functions, the assembly of these molecular machines is poorly understood. We investigate how presynaptic machinery is produced in the soma, trafficked throughout the axon, captured in nerve terminals, and assembled into functional molecular machines anchored to the presynaptic target membrane and aligned with postsynaptic receptors.
Active zone functions
It is known that synaptic vesicles containing neurotransmitters fuse exclusively at hot spots for release in presynaptic nerve terminals called active zones. Active zones are fascinating molecular machines that consist of a complex network of multi-domain proteins, orchestrating the ultrafast membrane trafficking process required for synaptic transmission. We are investigating the composition of active zones, how they operate, how their functions change during plasticity and learning, and how these changes tune behaviors.
Neuromodulation
Neuronal activity is regulated by an intriguing variety of non-classical neurotransmitters. Prominent neuromodulatory substances include neuropeptides, monoamines such as dopamine, and neurotrophins. The machinery that mediates neuromodulatory transmission, and the organization of their signaling structures, are poorly understood. We are dissecting the molecular apparatus that controls their release, assess release-receptor organization, define regulatory mechanisms, and determine their roles in the control of circuit function and behavior.
Key approaches
Studies in my laboratory are rooted in molecular and cellular approaches. We employ techniques including conditional gene targeting and genome editing, superresolution and electron microscopy, protein biochemistry, electrophysiology, optogenetics, functional imaging, and behavioral analyses.