Topic: Novel glutamate receptor signaling in the brain

Speaker: Prof. Pierre PAOLETTI

Time: 16:00-17:30 PM, 11 Jul. , 2025

Venue: Lecture hall 110, Lynn Library

Abstract:

Understanding how the activity of individual neurons ultimately relates to behavior in both normal and disease states is a central quest in neuroscience. To this end, it is essential to identify and dissect the various signaling mechanisms that drive and orchestrate cellular excitability and communication in the brain. Ionotropic glutamate receptors (iGluRs) play key roles in the CNS as effectors of excitatory neurotransmission at glutamatergic synapses. However, of the 18 mammalian iGluR genes, five do not respond to glutamate but rather to glycine or D-serine. Among these, GluN3, which belong to the NMDA receptor (NMDAR) family, and GluD have long been considered as oddities with a limited role in brain function. Recent studies from our laboratory and others have challenged this view. We have revealed that GluN3A receptors form excitatory glycine receptors (eGlyRs) that are enriched in emotional circuits and responsible for a novel signaling modality by which ambient glycine controls neuronal excitability and behavior. We also recently discovered that GluD1 receptors surprisingly bind GABA, the main inhibitory neurotransmitter in the brain, and accumulate at inhibitory synapses where they control inhibitory plasticity through a trans-synaptic, non-ionotropic mechanism. In the clinic, both GluN3A and GluD1 variants are risk factors in neuropsychiatric disorders. Altogether, these findings extend the scope of iGluR signaling in brain operation, with important implications for neurophysiology and drug development.

Brief introduction of the speaker:

Pierre Paoletti is Research Director at INSERM and Director of the Institute of Biology of the Ecole Normale Supérieure (IBENS, Paris), a joint ENS-CNRS-INSERM unit and leading European life sciences institute that brings together 28 research teams and >300 scientists in Genomics, Developmental Biology, Neuroscience, and Ecology & Evolution affiliated.

Dr. Paoletti obtained his Ph.D. in molecular and cellular neuroscience at the ENS and University Paris 6, and completed his postdoctoral training in ion channel biophysics at Columbia University in New York. Dr. Paoletti’s research addresses various aspects of neurotransmission and brain function. Together with his team, he has made influential contributions to our understanding of the structure, function and pharmacology of glutamate receptors, and their involvement in synapse plasticity, neuronal signaling and behavior. Dr. Paoletti has published >75 articles in journals such as Nature, Science, Neuron, Nature Neuroscience etc. totaling >14000 citations (Google Scholar), and has given numerous lectures in EU, UK, America and Asia. Dr. Paoletti received several honors and awards, including the FENS Young Investigator Award in 2010, an ERC Advanced Grant in 2016, the Grand Prix Lamonica de Neurologie in 2017, and was elected at the Academia Europaea in 2019 and at the French Academy of Sciences in 2024. He co-chaired the 2017 & 2019 Gordon Research Conferences on ‘Excitatory Synapses & Brain Function’ and, since 2015, has been a member of the editorial board of Current Opinion in Pharmacology.