BBS Faculty Member - Pascal Kaeser

Pascal Kaeser

Department of Neurobiology

Harvard Medical School
Armenise Building, Room 305
200 Longwood Avenue
Boston, MA 02115
Tel: 617-432-2093
Email: kaeser@hms.harvard.edu
Visit my lab page here.



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 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, which will reveal general mechanisms of neuromodulation. Understanding dopamine release will also provide a molecular framework to investigate aspects of neuro-psychiatric disorders.

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 in mice to electrophysiological and optogenetic analyses of synaptic activity to dissect their roles.



Last Update: 9/11/2013



Publications

For a complete listing of publications click here.

 


 

Kaeser PS, Deng L, Wang Y, Dulubova I, Liu X, Rizo J, Sudhof TC: RIM proteins tether Ca2+ channels to presynaptic active zones via a direct PDZ-domain interaction. Cell 2011, 144:282-295.

Kaeser PS, Deng L, Chavez AE, Liu X, Castillo PE, Sudhof TC: ELKS2alpha/CAST deletion selectively increases neurotransmitter release at inhibitory synapses.
Neuron 2009, 64:227-239.

Kaeser PS, Kwon HB, Chiu CQ, Deng L, Castillo PE, Sudhof TC: RIM1{alpha} and RIM1{beta} Are Synthesized from Distinct Promoters of the RIM1 Gene to Mediate Differential But Overlapping Synaptic Functions.
J. Neurosci. 2008, 28:13435-13447.

Kaeser PS, Kwon HB, Blundell J, Chevaleyre V, Morishita W, Malenka RC, Powell CM, Castillo PE, Sudhof TC: RIM1alpha phosphorylation at serine-413 by protein kinase A is not required for presynaptic long-term plasticity or learning.
Proc Natl Acad Sci U S A 2008, 105:14680-14685.



© 2013 by the President and Fellows of Harvard College