Zoltán Nusser
Diverse molecular mechanisms underlying heterogeneity in presynaptic release probability
The Brain Dynamics Graduate School invites you to the first keynote lecture at the Scientific Day '24:
Prof Dr Dr Dr Zoltán Nusser
Hungarian Research Network, Institute of Experimental Medicine HAS, Budapest, Hungary
"Diverse molecular mechanisms underlying heterogeneity in presynaptic release probability"
24th September 2024, 09:00
BBZ Seminar room
Deutscher Platz 5, 04103 Leipzig
Abstract:
It has been known for decades that chemical synapses of the CNS show tremendous functional and structural diversity. Understanding the molecular mechanisms underlying functional synaptic diversity is a major challenge and has been the focus of our research in the past decades. We investigated the mechanisms underlying different release probabilities of cerebellar glutamatergic and GABAergic synapses and found that distinct nano-topologies of the presynaptic voltage-gated Ca2+ channels and docked synaptic vesicles (SV) could explain the functional differences. Another example of synaptic diversity is the so-called postsynaptic target cell type-dependent variations in the presynaptic glutamate release in cortical circuits. The probability of glutamate release from hippocampal pyramidal cell (PC) axons that innervate oriens-lacunosum-moleculare (O-LM) interneurons is 10-fold lower than that innervating fast-spiking interneurons (FSINs). Our high-resolution immunolocalization experiments revealed that the nano-topology of synaptic vesicles and voltage-gated Ca2+ channels is very similar in these two hippocampal synapses, revealing that the same mechanism that underlies functional heterogeneity in the cerebellum is not present here. Pharmacological experiments demonstrated that the major difference between these two hippocampal synapses is their differential sensitivity to PDBU, indicating differential priming states of the SV. A sequential two-step priming model of synaptic transmission predicted a 6.5-fold smaller fraction of properly primed SVs at PC – O-LM synapses compared to those at PC – FSIN synapses. Our results demonstrate that incompletely primed SVs limit the output of PC – O-LM cell synapses and provide evidence for multiple presynaptic mechanisms underlying distinct presynaptic release properties.
Short Bio:
Zoltan Nusser graduated from the University of Oxford in 1995. Then, he studied cellular neurophysiology as a postdoctoral scientist in the laboratory of Stuart Cull-Candy at UCL, and in the laboratory of Istvan Mody at UCLA. In 2000, he established his research group in the Institute of Experimental Medicine, Budapest. His research interest focuses on understanding synaptic communication between nerve cells.
He has received a Postdoctoral Fellowship from the Boehringer Ingelheim Fonds (2000-2006), an International Research Scholarship from the Howard Hughes Medical Institute (2000-2005), and an International Senior Research Fellowship from the Wellcome Trust (2003-2006). He was also the recipient of a European Young Investigator Award (2006-2011) and two European Research Council Advanced Grants (2012-2017, 2018-2023). He was awarded the Ignaz L. Lieben Award of the Austrian Academy of Sciences in 2004, the FENS Boehringer Prize in 2006 and the Debiopharm Life Sciences Award in 2007. In 2007 he was elected as a fellow of the Hungarian Academy of Sciences and in 2011 Member of the Academia Europaea. He is currently the deputy director of the Institute of Experimental Medicine, Budapest, Hungary.