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
Mechanisms of neuromodulatory volume transmission.
Authors: Authors: Özçete ÖD, Banerjee A, Kaeser PS.
Mol Psychiatry
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The intracellular C-terminus confers compartment-specific targeting of voltage-gated Ca2+ channels.
Authors: Authors: Chin M, Kaeser PS.
bioRxiv
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Molecular definition of distinct active zone protein machineries for Ca2+ channel clustering and synaptic vesicle priming.
Authors: Authors: Emperador-Melero J, Andersen JW, Metzbower SR, Levy AD, Dharmasri PA, de Nola G, Blanpied TA, Kaeser PS.
bioRxiv
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Synaptotagmin-1 is a Ca2+ sensor for somatodendritic dopamine release.
Authors: Authors: Lebowitz JJ, Banerjee A, Qiao C, Bunzow JR, Williams JT, Kaeser PS.
Cell Rep
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Protein composition of axonal dopamine release sites in the striatum.
Authors: Authors: Kershberg L, Banerjee A, Kaeser PS.
Elife
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An action potential initiation mechanism in distal axons for the control of dopamine release.
Authors: Authors: Liu C, Cai X, Ritzau-Jost A, Kramer PF, Li Y, Khaliq ZM, Hallermann S, Kaeser PS.
Science
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Rebuilding essential active zone functions within a synapse.
Authors: Authors: Tan C, Wang SSH, de Nola G, Kaeser PS.
Neuron
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Molecular and functional architecture of striatal dopamine release sites.
Authors: Authors: Banerjee A, Imig C, Balakrishnan K, Kershberg L, Lipstein N, Uronen RL, Wang J, Cai X, Benseler F, Rhee JS, Cooper BH, Liu C, Wojcik SM, Brose N, Kaeser PS.
Neuron
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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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