Plenary Lectures
Michael Anderson
MRC Cognition and Brain Sciences Unit at the University of Cambridge. UK.
Brain Mechanisms underlying the inhibitory control of thought.
Controlling action and thought requires the capacity to stop mental processes. Over the past two decades, evidence has grown that a domain-general inhibitory control mechanism supported by the right lateral prefrontal cortex achieves these functions. However, current views of the neural mechanisms of inhibitory control derive largely from research into the stopping of action. Whereas action stopping is a convenient empirical model, it does not invoke thought inhibition and cannot be used to identify the unique features of this process. Here, we review research that addresses how organisms stop a key process that drives thoughts: memory retrieval. This work has shown that retrieval stopping shares right dorsolateral and ventrolateral prefrontal mechanisms with action stopping, consistent with a domain-general inhibitory control mechanism, but also recruits a distinct fronto-temporal pathway that determines the success of mental control. As part of this pathway, GABAergic inhibition within the hippocampus influences the efficacy of prefrontal control over thought. These unique elements of mental control suggest that hippocampal disinhibition is a transdiagnostic factor underlying intrusive thinking, linking the fronto-temporal control pathway to preclinical models of psychiatric disorders and fear extinction. We suggest that retrieval-stopping deficits may underlie the intrusive thinking that is common across many psychiatric disorders.
Bassem Hassan
Paris Brain Institute and Yale School of Medicine
Developmental emergence of brain individuality
The Nature versusNurture debate has generally been considered from the lens of genome versus experience dichotomy and has dominated our thinking about behavioral individuality and personality traits. In contrast, the role of nonheritable noise during brain development in behavioral variation is understudied. Using the Drosophila melanogaster visual system, I will discuss our efforts to dissect how individuality in circuit wiring emerges during development, and how that helps generate individual behavioral variation.
Manuel Mameli
The University of Lausanne
Neural Circuit Mechanisms for Aversion Processing
Appropriate behavioral strategies when facing aversive experience are necessary for the individual survival. I will present latest results describing lateral habenula’s role in shaping approach and avoidance behaviors. I will highlight how synaptic strength, circuit assembly, and neuronal dynamics contribute to adaptive behavioral responses following environmental threats. Using electrophysiological and imaging approaches I will provide evidence that lateral habenula neurons excitation is a requirement during encoding of threats of different nature spanning from predator attack to newborn vocalisation. I will provide a framework whereby habenular activity represents a switchboard determinant in the transition to physiological threat encoding and pathological negative affect. Altogether this will provide the audience with a general understanding of the neural circuit underlying decision-making and emotional states in health and pathology.
Gabriela Salvador
INIBIBB Bahia Blanca
Molecular Mechanisms Underlying Neuron-Glia Metabolic Interactions in Neurodegeneration
Neurodegenerative processes are increasingly understood as metabolic disorders in which neuron–glia interactions critically regulate lipid homeostasis and redox status. Our work has focused on identifying the molecular mechanisms underlying neurotoxicity triggered by oxidative stress, proteotoxicity, iron dyshomeostasis, and pesticide exposure. Early studies from our lab demonstrated that α-synuclein modulates SREBP-dependent transcription, leading to alterations in fatty acid and cholesterol metabolism, thereby reshaping cellular responses to oxidative stress.
Building on these findings, we subsequently identified the involvement of molecular components of lipid-dependent resolution pathways. These mechanisms were shown to modulate neuroinflammatory and oxidative processes, highlighting their role in controlling lipid peroxidation and promoting adaptive responses in neurons.
More recently, studies using in vivo models of iron overload and pesticide exposure have revealed profound alterations in neutral lipid metabolism, including cholesterol accumulation and increased triacylglycerol hydrolysis. These changes are accompanied by dopaminergic neurodegeneration and motor impairments. Importantly, these alterations are tightly associated with ferroptosis and depend on intercellular metabolic interactions, in which glial cells actively contribute to neuronal lipid remodeling.
Collectively, our findings support the concept that neurodegenerative processes can be understood as lipidopathies driven by dysregulated neuron–glia metabolic interactions. Targeting the molecular pathways that govern lipid homeostasis and resolution responses may provide novel therapeutic strategies for neurodegenerative diseases.
Sara A. Solla
Department of Neuroscience, Northwestern University
Low Dimensional Neural Manifolds for the Control of Movemen
The ability to simultaneously record the activity from tens to hundreds to thousands of neurons has allowed us to analyze the computational role of population activity as opposed to single neuron activity. Recent work on a variety of cortical areas suggests that neural function may be built on the activation of population-wide activity patterns, the neural modes, rather than on the independent modulation of individual neural activity. These neural modes, the dominant covariation patterns within the neural population, define a low dimensional neural manifold that captures most of the variance in the recorded neural activity. We refer to the time-dependent activation of the neural modes as their latent dynamics and argue that latent cortical dynamics within the manifold are the fundamental and stable building blocks of neural population activity. A focus on motor cortex provides a model for neural control of movement in which "neural modes" are the generators of motor behaviors. We review existing evidence in support of neural manifolds, and present novel results on the relation between latent dynamics, muscle activity, and limb control. A method to align the latent dynamics associated with a simple task allows us to track manifold activity across time and across primates.