Zoltán Molnár is Professor of Developmental Neuroscience at the University of Oxford. He is known for key contributions to our understanding of how the birth of cortical neurons is regulated, how they migrate, differentiate, generate axons and assemble into circuits, and how those circuits change over time, partly as a result of activity passing through them. Molnár earned his M.D. at the Albert Szent-Györgyi Medical University, Szeged, Hungary and D.Phil. at the University of Oxford, UK. He also investigated thalamocortical development working at the Institut de Biologie Cellulaire et de Morphologie, Université de Lausanne, Switzerland, and learned optical recording techniques to understand early functional thalamocortical interactions at Kyoto Prefectural School of Medicine, Japan. He was appointed to a University Lecturer position at the Department of Human Anatomyc and Genetics at Oxford associated with an Official Fellowship and Tutorship at St John’s College from 2000. He was awarded the title Professor of Developmental Neuroscience in 2007. Molnar has been Elected Member of Academia Europaea (Physiology and Neuroscience); European Neonatal Brain Club; Fellow of Royal Society of Biology, Fellow of the Anatomical Society, Awarded New Fellow of the Year Award for 2018.
Differential role of snare proteins in various cortical projection neuron populations
Abstract: Neural communication in the adult nervous system is mediated primarily through chemical synapses, where action potentials elicit Ca 2+ signals, which trigger vesicular fusion and neurotransmitter release in the presynaptic compartment.The study of the role of specific proteins of the synaptic vesicle release machinery in the establishment, plasticity, and maintenance of neuronal connections during development has only recently become possible, with the advent of mouse models where various members of the N-ethylmaleimide- sensitive factor attachment protein receptor (SNARE) complex have been genetically manipulated. I shall provide an overview of these models, focusing on the role of regulated vesicular release and/or cellular excitability in synaptic assembly, development and maintenance of cortical circuits, cell survival, circuit level excitation–inhibition balance, myelination, refinement, and plasticity of key axonal projections from the cerebral cortex. Synaptosomal associated protein 25 kDa (SNAP25) is an essential component of the SNARE complex regulating synaptic vesicle fusion. SNAP25 deficiency has been implicated in a variety of cognitive disorders. We ablated SNAP25 from selected neuronal populations by generating a transgenic mouse (B6-Snap25tm3mcw (Snap25-flox)) with LoxP sites flanking exon5a/5b. In the presence of Cre-recombinase, Snap25-flox is recombined to a truncated transcript. We studied Snap25 cKO in subsets of cortical projection neurons in vivo (L5—Rbp4-Cre; L6—Ntsr1-Cre; L6b—Drd1a-Cre). cKO neurons develop normal axonal projections, but axons are not maintained appropriately, showing signs of swelling, fragmentation and eventually complete absence. Onset and progression of degeneration are dependent on the neuron type, with L5 cells showing the earliest and most severe axonal loss. Ultrastructural examination revealed that cKO neurites contain autophagosome/lysosome-like structures. Markers of inflammation such as Iba1 and lipofuscin are increased only in adult cKO cortex. These models are important for understanding various developmental and psychiatric conditions, and neurodegenerative diseases.
References:
https://doi.org/10.1093/cercor/bhy127
