Plenary Lectures

Presidential Lecture

AMPA Receptor Nanoscale Dynamics in Synaptic Plasticity: From Fundamental Mechanisms to Novel Regulatory Pathways

Daniel Choquet

Bordeaux Neurocampus
Bordeaux University (Bordeaux, FR)

Abstract

AMPA receptor (AMPAR) nanoscale organization and dynamics critically regulate synaptic transmission and plasticity. We have demonstrated that AMPARs undergo continuous lateral diffusion, dynamically entering and exiting synapses. This process governs short- and long-term plasticity by modulating receptor availability and synaptic strength. Recent findings reveal novel extracellular and intracellular mechanisms regulating AMPAR nanoscale organization, impacting learning and memory. By integrating high-resolution imaging and molecular manipulation, we uncover how AMPAR mobility orchestrates synaptic integration and plasticity across neuronal networks. These insights provide a refined understanding of excitatory transmission and unveil potential targets for neuropsychiatric and neurodegenerative disorders.

Bio

Daniel Choquet obtained an engineering degree from Ecole Centrale in 1984 and a PhD in neuroscience at the Pasteur Institute, studying ion channels in lymphocytes. He joined CNRS in 1988 and did a postdoc at Duke University on integrin-cytoskeletal linkages with Michael Sheetz. He settled in Bordeaux in 1996, focusing on high-resolution imaging of neurotransmitter receptor trafficking. He founded the Institute for Interdisciplinary Neuroscience and the Bordeaux Imaging Center. He has a long standing interest in understanding how the dynamic nanoscale organization of synapses determines their function and plasticity. To this aim, his group combines high resolution imaging, cell biology, protein engineering and physiology. Recently, he has focused on identifying the contributions of pre and post-synaptic components to short and long term synaptic plasticity and their dysregulation in neurodevelopmental diseases. This is achieved developing new approaches to monitor and manipulate receptor trafficking and protein-protein interactions in brain slices and in vivo. He is a member of the French Academy and recipient of 3 ERC advanced grants.

Sensory and Motor Systems

The Odds of a Decision

Matteo Carandini

CortexLab
UCL – University College London (London, UK)

Abstract

To make a decision, we must often combine diverse factors such as sensory inputs, past actions, and estimates of value. There is increasing evidence that the brain does this via a simple operation involving sums and multiplications. This operation is common in machine learning, economics, and psychology. Its neural correlates can be identified in mice thanks to large-scale neural recordings and localized inactivations. These methods reveal how an audiovisual choice is computed at key stages in visual cortex, auditory cortex, prefrontal cortex, and superior colliculus. The results reveal a single view of how the brain makes a variety of decisions.

Bio

Matteo Carandini is the GlaxoSmithKline / Fight for Sight Professor of Visual Neuroscience at University College London, where he co-directs the Cortexlab. Carandini’s research focuses on the computations performed by large populations of neurons in the mouse brain, the underlying circuits, and the resulting impact on behavior. He is a leader of the Neuropixels consortium, which develops next-generation probes to record from large populations of neurons (www.ucl.ac.uk/neuropixels). He is a founding member of the International Brain Laboratory, a consortium of 21 laboratories in 6 countries who seek to understand the basis of decision-making in the whole mouse brain (www.internationalbrainlab.org).

Disorders of the Nervous System

Circuits Dissection in Neurodevelopmental Disorders from Mechanisms to Therapeutic Windows

Michela Fagiolini

Institute of Neuroscience
CNR (Pisa, Italy)

Abstract

Experience-dependent critical periods are windows of heightened plasticity during early brain development, essential for the maturation of sensory, cognitive, and social functions. In this lecture, I will present recent advances from preclinical and clinical studies investigating how distinct classes of inhibitory interneurons regulate cortical processing in health and neurodevelopmental disorders. I will discuss how alterations in these inhibitory circuits contribute to circuit dysfunction and atypical sensory processing. Finally, I will highlight translational strategies aimed at restoring plasticity and rebalancing inhibitory control later in life, offering a roadmap for novel therapeutic interventions.

Bio

Michela Fagiolini, Ph.D., is an internationally trained neuroscientist whose work has significantly advanced our understanding of critical periods of brain development and their disruption in neurodevelopmental disorders. She received her degree from the Scuola Normale Superiore in Pisa and pursued postdoctoral research at the University of California, San Francisco (UCSF) and the RIKEN Brain Science Institute in Japan. Throughout her career, she has bridged preclinical and clinical research, with a focus on translating fundamental discoveries into therapeutic strategies. She is Associate Professor of Neurology at Boston Children’s Hospital and Harvard Medical School, and currently serves as Director of the Institute of Neuroscience of the National Research Council (CNR) in Italy, leading initiatives to foster innovation and collaboration across international neuroscience communities.

Cognition and Behavior

How Does Context and Experience Shape Social Fear Circuits?

Cornelius Gross

European Molecular Biology Laboratory
EMBL Rome (Rome, IT)

Abstract

Exposure to predators or predator-like stimuli elicit powerful negative emotions and uncontrollable escape responses across animal species. Over the last decade we have dissected the brain circuits that mediate such innate threat responses in mice in order to learn more about human fear. We have identified the subcortical pathways that mediate innate responses to predators and shown that these are independent from those that mediate responses to social threats. We have recorded the responses of individual neurons while animals initiate escape from threat and have identified local hypothalamic and brainstem microcircuits that supports the escape decision. More recently, we have found that social hierarchy and social context can modulate the threshold for escape, showing that innate emotional behavior responses can be reshaped by experience. We are currently exploring how territoriality impacts social fear and aggression, and how our neurocircuit findings in the mouse may be relevant for human social behavior.

Bio

Dr. Gross was raised in the United States and received undergraduate training in spectroscopy and biophysics at the University of California, Berkeley and then pursued doctoral research at Yale University studying transcriptional regulation under William McGinnis. Following the award of his PhD, Dr. Gross served as a public high school teacher in New York City where he gained an appreciation for the benefits and challenges of communicating science to a lay audience. Inspired by his work with high school students, Dr. Gross eventually returned to the laboratory to continue his research career in the field of behavioral neuroscience.
As a postdoctoral fellow in the group of René Hen at Columbia University he discovered a developmental role for serotonin in determining anxiety behavior in mice and identified the serotonin receptor responsible for the therapeutic effects of antidepressants. In 2003 he established his independent group at the European Molecular Biology Laboratory (EMBL).
Early work from the group showed how serotonin moderates the impact of maternal care on anxiety and how deficits in serotonin autoregulation can cause sudden infant death syndrome. During this period he also worked extensively on the role of microglia in shaping the developing brain and published a landmark paper (cited over 3400 times) that founded the field of microglia and synaptic remodeling. In 2010 Dr. Gross undertook a major refocusing of his laboratory and embarked on a series of studies characterizing the hypothalamic and brainstem circuits that regulate social and predator fear. Current work in the laboratory aims
to understand how local circuitry in these areas process social threat information, how they calculate escape decisions, and how these decisions are adapted to territorial context and social experience. His long-term goal is to identify cellular, circuit, and molecular mechanisms that can inform our understanding of emotional decision making and adaptation to social threat in humans.
Dr. Gross has served on institutional advisory boards across the world, he is an adjunct professor at Monash University in Melbourne, and has been a chair of the ERC Consolidator Grant Neuroscience Panel since 2018. In 2022 he was inducted as an EMBO Member. His laboratory has been funded by numerous private foundations, as well as the US National Institutes of Health (NIH & NIEHS) and the European Commission, and he has twice been awarded an Advanced Grant from the European Research Council (ERC). Dr. Gross is currently Senior Scientist and Interim Head of the Epigenetics & Neurobiology Unit of EMBL in Rome, Italy.

Development

Building Functional Sensory Circuits: Unraveling the Role of Spontaneous Activity in modality-specificity

Guillermina López-Bendito

Instituto de Neurociencias
UMH-CSIC (Alicante, ES)

Abstract

Spontaneous thalamic waves of activity propagate to the cortex during normal embryonic development, influencing the organization of cortical structures. Our group has pioneered the study of the role of these thalamic waves in the development of sensory maps and cortical columns, the functional unit of the cortex. These studies have revealed that structured patterns of neuronal activity in the thalamus of mouse embryos sculpt the functional columns in the cortex and the concomitant functional somatotopic map, a process that occurs during immature cortical stages. Using in vivo calcium imaging in intact mouse embryos, we identified that the fundamental columnar organization of the thalamocortical somatotopic map already exists before birth. Our laboratory provided the first causal link between intrinsic thalamic activity in the embryo and cortical map formation. Recently, our lab has demonstrated that sensory circuits emerge as nonsegregated modules and that at birth these circuits became segregated and sensory modalities specified. By doing sensory circuit stimulation in mouse embryos in vivo, we found, unexpectedly, that this segregation takes place in an evolutionary ancient subcortical structure, the superior colliculus, in a process that depends on the earliest activity from the retina. This work has now changed the way we understand the development of sensory circuits and has opened several lines of research in the frontier of knowledge. In my talk I will show these relevant data and discuss new unpublished results on the interplay between genetic programs and patterns of spontaneous activity in developing cortical areas and how this interaction might be used as a tool to predict circuit development and early sensory plasticity.

Bio

Full Professor from Spanish National Research Council (CSIC) and Leader of the group “Development, Plasticity and Reprogramming of Sensory Circuits” at the Developmental Neurobiology Unit of the Institute of Neurosciences (IN), Alicante, Spain; where she is also Head of the Developmental Neurobiology Department, since 2020. In Oct 2024 she has been elected co-deputy Director of the IN.
Dr. López-Bendito´s lab studies the development and plasticity of brain circuits. They discovered that sensory representations emerge while circuits are being assembled in embryonic life and that spontaneous activity helps to construct these early circuits. Briefly, their research has pioneered three essential aspects of neurodevelopment. First, they contributed to determining the molecular mechanisms involved in the construction of sensory circuits in the brain. Second, her lab revealed the involvement of spontaneous brain activity in the formation of these circuits during fetal development. Finally, their research program on plasticity and cell reprogramming in the developing brain is aimed at the recovery of brain circuits after the early loss of a sensory organ. The long-term aspiration of her lab is designing tools to restore defective neuronal connections in patients with sensory deficits (e.g. blindness or deafness).
Prof López-Bendito has led, as principal investigator, six consecutive national projects of the Spanish State Research Plan, a project of the La Caixa Foundation, two PROMETEO projects of excellence from the Valencian Community, and three consecutive projects from the European Research Council (Starting, Consolidator and Advanced grants), as well as coordinating a Human Frontier Science Program grant.
She has received prestigious awards and distinctions, including the “Hipatia Award” to her Scientific trajectory from elEconomista (2022), selected team of Mediterranean scientists from Mednight (2021), the Banc Sabadell Foundation Award for Biomedical Research (2020), the “Constantes y Vitales” Award from AtresMedia (2019), the Scientific Merit Award from the Valencian Community, the Joseph Altman award Prize in Developmental Neurobiology (2018) or the IBRO-Kemali award (2017), among others.
She is an EMBO member and currently the chair of the EMBO YIP selection committee. She is also a member of Joseph Altman Award Selection committee, member of the Committee of Scientific Experts of the Museum of Arts and Sciences of Valencia and in 2022 elected Corresponding Academic of the Royal Academy of Exact, Physical and Natural Sciences of Spain.

Novel Methods and Technology Development

On the Electrophysiological Consequences of Brain Injury

Marcello Massimini

Department of Biomedical and Clinical Sciences
University of Milan (Milan, IT)

Fondazione Don Carlo Gnocchi IRCCS (Milan, IT)

Abstract

By connecting old and recent notions, different spatial scales, and research domains, I will introduce a novel framework on the consequences of brain injury focusing on a key role of slow waves. I will argue that the long-standing finding of EEG slow waves after brain injury reflects the intrusion of sleep-like cortical dynamics during wakefulness; I will illustrate how these dynamics are generatedand how they can lead to functional network disruption and behavioralimpairment. Finally, I will outline a scenario whereby post-injury slow waves can be modulated to reawaken parts of the brain that have fallen asleep to optimize rehabilitation strategies and promote recovery.

Bio

Marcello Massimini, was trained as a Medical Doctor, received a PhD in Neurophysiology and is currently Professor of Physiology at the University of Milan and fellow of the Canadian Institute of Advanced Research. He worked at Laval University (CA) in the lab of Mircea Steriade and at the University of Wisconsin (USA) with Giulio Tononi. Spanning from in vivo intracellular recordings to neuroimaging, EEG and TMS-EEG in humans, his whole research activity has been devoted to understanding the consequences of brain injury and what changes in cortical circuits when consciousness fades and recovers. On these subjects he received several awards, grants (recently, an ERC Synergy), published papers in high impact journals and a book (“Sizing up Consciousness”) for Oxford University Press.