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Kaeser Lab

Department of Neurobiology
Harvard Medical School


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Our goal is to understand molecular mechanisms that underlie functions and plasticity of release sites for neurotransmitters and neuromodulators.

My laboratory is interested in molecular mechanisms at presynaptic neurotransmitter release sites called active zones that participate in controlling microcircuit functions, and we pursue three missions.

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.

Active zone assembly. While the past decades have revealed many fascinating molecular mechanisms that underlie active zone functions, the assembly of thse 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.     

Neuromodulation. Neuronal activity is regulated by an intriguing variety of non-classical neurotransmitters called neuromodulators. Prominent neuromodulatory substances include neuropeptides, monoamines such as dopamine, and neurotrophins. The machinery that mediates their release is poorly understood. We are dissecting the molecular apparatus that controls release of dopamine and other neuromodulators. We further assess their release-receptor organization, mechanisms that regulate neuromodulation, and dissect roles of neuromodulators in the control of circuit function and behavior. 

Studies in my laboratory are rooted in molecular and biochemical methods to identify novel components and protein interactions at neuronal release sites. We employ techniques including conditional gene targeting and genome editing in mice, superresolution and electron microscopy, electrophysiology, optogenetics, functional imaging of synaptic and circuit activity, and behavioral analyses.

 


 

Kaeser Lab | Harvard Medical School | Department of Neurobiology | Armenise 315 | 200 Longwood Ave | Boston MA 02115