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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.

Neurons predominantly communicate through fast neurotransmission at synapses. Synaptic and neuronal activity levels are tightly controlled, and adjusted to changes in demand. Prominent cellular events that underlie these adaptations are synaptic plasticity and neuromodulation via release of non-classical transmitters. My laboratory is interested in molecular mechanisms at presynaptic neurotransmitter release sites called active zones that participate in controlling neuronal activity, and we pursue two missions.


(1) 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 they change during plasticity and learning, and how these changes tune behaviors.


(2) Neuronal activity is regulated by an intriguing variety of non-classical neurotransmitters called neuromodulators. Prominent neuromodulatory substances include a multitude of neuropeptides, monoamines such as dopamine, and neurotrophins. The machinery that mediates their release, however, is poorly understood. We are dissecting the molecular apparatus that controls release of dopamine and other neuromodulatory substances to uncover mechanisms of neuromodulation.

Studies in my laboratory are founded on molecular and biochemical methods to identify novel components and protein interactions at neuronal release sites. We employ techniques ranging from conditional gene targeting and genome editing in mice to electrophysiology, optogenetics and functional imaging of synaptic activity to dissect their roles.

 


 

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