Pascal Kaeser
Pascal Kaeser, MD
Professor of Neurobiology

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.

 

"My laboratory is interested in molecular mechanisms at presynaptic neurotransmitter release sites that participate in controlling neuronal activity."

Publications View
Presynaptic short-term plasticity persists in the absence of PKC phosphorylation of Munc18-1.
Authors: Authors: Wang CC, Weyrer C, Fioravante D, Kaeser PS, Regehr WG.
J Neurosci
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PKC-phosphorylation of Liprin-a3 triggers phase separation and controls presynaptic active zone structure.
Authors: Authors: Emperador-Melero J, Wong MY, Wang SSH, de Nola G, Nyitrai H, Kirchhausen T, Kaeser PS.
Nat Commun
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Spatial and temporal scales of dopamine transmission.
Authors: Authors: Liu C, Goel P, Kaeser PS.
Nat Rev Neurosci
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Intact synapse structure and function after combined knockout of PTPd, PTPs and LAR.
Authors: Authors: Emperador-Melero J, de Nola G, Kaeser PS.
Elife
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Synapse and Active Zone Assembly in the Absence of Presynaptic Ca2+ Channels and Ca2+ Entry.
Authors: Authors: Held RG, Liu C, Ma K, Ramsey AM, Tarr TB, De Nola G, Wang SSH, Wang J, van den Maagdenberg AMJM, Schneider T, Sun J, Blanpied TA, Kaeser PS.
Neuron
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ELKS1 Captures Rab6-Marked Vesicular Cargo in Presynaptic Nerve Terminals.
Authors: Authors: Nyitrai H, Wang SSH, Kaeser PS.
Cell Rep
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Synaptotagmin-1 is the Ca2+ sensor for fast striatal dopamine release.
Authors: Authors: Banerjee A, Lee J, Nemcova P, Liu C, Kaeser PS.
Elife
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Assembly of the presynaptic active zone.
Authors: Authors: Emperador-Melero J, Kaeser PS.
Curr Opin Neurobiol
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Optimizing Nervous System-Specific Gene Targeting with Cre Driver Lines: Prevalence of Germline Recombination and Influencing Factors.
Authors: Authors: Luo L, Ambrozkiewicz MC, Benseler F, Chen C, Dumontier E, Falkner S, Furlanis E, Gomez AM, Hoshina N, Huang WH, Hutchison MA, Itoh-Maruoka Y, Lavery LA, Li W, Maruo T, Motohashi J, Pai EL, Pelkey KA, Pereira A, Philips T, Sinclair JL, Stogsdill JA, Traunmüller L, Wang J, Wortel J, You W, Abumaria N, Beier KT, Brose N, Burgess HA, Cepko CL, Cloutier JF, Eroglu C, Goebbels S, Kaeser PS, Kay JN, Lu W, Luo L, Mandai K, McBain CJ, Nave KA, Prado MAM, Prado VF, Rothstein J, Rubenstein JLR, Saher G, Sakimura K, Sanes JR, Scheiffele P, Takai Y, Umemori H, Verhage M, Yuzaki M, Zoghbi HY, Kawabe H, Craig AM.
Neuron
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Nanoscale Location Matters: Emerging Principles of Ca2+ Channel Organization at the Presynaptic Active Zone.
Authors: Authors: Liu C, Kaeser PS.
Neuron
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