Department of Neurobiology

Research

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 and function
Active zones are fascinating molecular machines that consist of networks of multi-domain proteins, orchestrating the ultrafast membrane trafficking process required for synaptic transmission. We investigate how these molecular machines are produced in the soma, trafficked along the axon, captured in nerve terminals, and assembled into functional release sites anchored to the presynaptic target membrane. We are dissecting how these machines operate during fusion and how their functions change during plasticity and learning to tune circuit function and behavior.

Neuromodulation
Neuronal activity is regulated by an intriguing variety of non-classical neurotransmitters, which often operate through volume transmission. The machinery that mediates neuromodulatory transmission, and the organization of their signaling structures, are poorly understood. We are dissecting the molecular apparatus that controls the release of modulatory transmitters, assess release-receptor organization, define regulatory mechanisms, and determine their roles in the control of circuit function and behavior. Our current focus includes work on dopamine, serotonin, norepinephrine, actylcholine and neuropeptides.

Key approaches
Studies in our 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.