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The Distinguished Seminar Series features presentations by outstanding thinkers and scientists, sponsored by the Allen Institute for Brain Science. At this seminar, Brian Dias presents “Understanding and breaking legacies of stress.”
The Distinguished Seminar Series features presentations by outstanding thinkers and scientists, sponsored by the Allen Institute for Brain Science. Distinguished speakers are selected based on the impact of their interdisciplinary research to the neuroscience community. Speakers spend a full day visiting with research staff, are nominated by members of the Allen Institute, and selected by a committee of peers.
We welcome members of the broader community to join us for these open seminars. See below for a schedule of upcoming speakers and view video presentations from past speakers. Register for the upcoming seminars below.
Historical events have generated data indicating that stressors experienced by populations, affect not only the individuals directly exposed to them, but also descendants. My talk will shed light on the nature and mechanisms by which legacies of stress perpetuate across generations, and how we may begin to break them.
Brian Dias is an Assistant Professor in the Department of Pediatrics at the USC Keck School of Medicine and directs a research laboratory in the Developmental Neuroscience & Neurogenetics Program at The Saban Research Institute, Children’s Hospital Los Angeles. Dr. Dias’ research seeks to understand how mammalian neurobiology, physiology and reproductive biology is impacted by stress or trauma, and how parental legacies of stress or trauma influence offspring. Armed with this understanding, Dr. Dias and his team aim to inform therapeutic and policy interventions to ameliorate the effects of stress or trauma in both, ancestral and descendant populations. Toward this goal, Dr. Dias uses molecular, cellular, genetic, epigenetic, physiological, and behavioral approaches to investigate how the biology of an organism and its responsiveness to stress or trauma is influenced by micro- (genome, epigenome and hormones), and macro-environments (ancestral, in utero and post-natal experiences). Among other outlets, Dr. Dias’ work has been featured in Nature, on the BBC, and in a list of the 10 Most Important Discoveries of 2014 published by La Recherche Magazine. Most recently, he was quoted about the legacy of trauma (BBC), the neurobiology of family separation (BrainFacts), and gave a TEDx talk on Halting Legacies of Trauma. In 2017, Dr. Dias was awarded a CIFAR Azrieli Global Scholar Award (competitive awards given to exceptional early career investigators from around the world by the Canadian Institute for Advanced Research (CIFAR), and is currently a Fellow in CIFAR’s Child & Brain Development Program. In 2019, Dr. Dias was selected to be part of the Young Leader network at the Science & Technology in Society Forum in Kyoto, Japan (an invitation-only forum that includes world leaders and diplomats discussing how science and technology can address roadblocks to human progress). In addition to his research, Dr. Dias is interested in education and knowledge mobilization. This interest has seen Dr. Dias participate in Sci-Foo Camp at Google – an invitation-only ideas festival that is often described as a mini-Woodstock of ideas. Dr. Dias is a faculty member of the Emory Tibet Science Initiative, teaches Neuroscience to Tibetan Buddhist monastics, and participated on a panel discussing “Consciousness” with scholars that included the Dalai Lama. More information is available at his lab website.
Septal nuclei in the basal forebrain have critical roles in regulating emotional states including fear, anxiety, and aggression. Dysfunction of septal neurons is thought to play a significant role in the pathophysiology of a variety of psychiatric disorders including schizophrenia, bipolar disorder and depression. The septum can be classified into medial (MS)and lateral (LS) regions. The medial septum is composed of cholinergic, GABAergic and glutamatergic neurons that primarily project to the hippocampus. The lateral septum is composed of a diverse array of GABAergic projection neurons that have reciprocal connections with numerous brain regions known to regulate emotional and motivational states. It is currently unclear how septal neuronal diversity and circuit wiring are specified during development. Using molecular genetics and single-cell/nuclei RNA-seq we have begun to unravel the developmental logic for producing diverse neural cell types in the septum. Our future work is focused on understanding the specific contribution of developmentally specified neural cell types in the regulation of internal states carried out by the septum.
Corey Harwell is an Associate Professor in the Department of Neurology at the University of California, San Francisco. His lab studies the cellular and molecular mechanisms that underlie the production and assembly of circuits in the developing brain. Over the course of development numerous molecules are re-purposed to function in distinct cellular contexts. This is particularly evident during nervous system development, where cellular functions change drastically during maturation of the earliest born neurons and the establishment and then refinement of their synaptic connections. In his current work, he is taking a multi-disciplinary research strategy to identify the developmental mechanisms that regulate neural diversity and circuity assembly in the mammalian forebrain.
Psychological and neurophysiological studies of decision-making have focused primarily on scenarios in which subjects are faced with abstract choices that are stable in time. This has led to serial models which begin with the representation of relevant information about costs and benefits, followed by careful deliberation about the choice, followed by action planning and execution. However, the brain evolved to interact with a dynamic and constantly changing world, in which the choices themselves as well as their relative costs and benefits are defined by the momentary geometry of the immediate environment and are continuously changing during ongoing activity. To deal with the demands of real-time interactive behavior, animals require a neural architecture in which the sensorimotor specification of potential actions, their valuation, selection, and even execution can all take place in parallel. I will describe a general hypothesis for how the brain deals with the challenges of such dynamic and embodied behavior, and present the results of a series of behavioral and neurophysiological experiments in which humans and monkeys make decisions on the basis of sensory information that changes over time. These experiments suggest that sensory information pertinent to decisions is processed quickly and combined with a growing signal related to the urge to act, and the result biases a competition between potential actions that takes place within the same sensorimotor circuits that guide action.
Paul Cisek is a full professor in the Department of Neuroscience at the University of Montreal. He has a background in computer science and artificial intelligence, doctoral training in computational neuroscience with Stephen Grossberg and Daniel Bullock, and postdoctoral training in neurophysiological recording in non-human primates with Stephen Scott and John Kalaska. His work combines these techniques into an interdisciplinary approach to understanding how the brain controls our interactions with the world. In particular, his theoretical work suggests that the brain is organized as a system of parallel sensorimotor streams that have been differentiated and elaborated over millions of years of evolution, and his empirical work investigates the neural dynamics of how potential actions are specified and how they compete in the cortical and subcortical circuits of humans and other primates.
In the first part of my talk, I will discuss our recent work on the midbrain dopamine system. The hypothesis that midbrain dopamine (DA) neurons broadcast an error signal for the prediction of reward is among the great successes of computational neuroscience. However, our recent results contradict a core aspect of this theory: that the neurons uniformly convey a scalar, global signal. I will review this work, as well as our new efforts to update models of the neural basis of reinforcement learning with our data. In the second part of my talk, I will discuss our recent findings of state-dependent decision-making mechanisms in the striatum.
Ilana Witten is a professor of neuroscience and psychology at Princeton University. She was first introduced to neuroscience as an undergraduate physics major, when she studied neural coding in the retina with Michael Berry at Princeton. She then moved to Stanford to pursue a PhD in neuroscience, where she worked in the systems neuroscience lab of Eric Knudsen. As a postdoctoral fellow, she worked with Karl Deisseroth in the Department of Bioengineering at Stanford, developing and applying optogenetic tools to dissect the neuromodulatory control of reward behavior in rodents. Since 2012, her lab at the Neuroscience Institute and Department of Psychology at Princeton has focused on understanding the circuitry in the striatum that support reward learning and decision making. She has received multiple awards for her work, including an NIH New Innovator Award, a Mcknight Scholars Award, and the Daniel X Freedman Prize.
Prof. Mackenzie Mathis is the Bertarelli Foundation Chair of Integrative Neuroscience and an Assistant Professor at the Swiss Federal Institute of Technology, Lausanne (EPFL). Following the award of her PhD at Harvard University in 2017 with Prof. Naoshige Uchida, she was awarded the prestigious Rowland Fellowship at Harvard to start her independent laboratory (2017-2020). Before starting her group, she worked with Prof. Matthias Bethge at the University of Tübingen in the summer of 2017 with the support of the Women & the Brain Project ALS Fellowship. She is an ELLIS Scholar, a former NSF Graduate Fellow, and her work has been featured in the news at Bloomberg BusinessWeek, Nature, and The Atlantic. She was awarded the FENS EJN Young Investigator Prize 2022.
Her lab works on mechanisms underlying adaptive behavior in intelligent systems. Specifically, the laboratory combines machine learning, computer vision, and experimental work in rodents with the combined goal of understanding the neural basis of adaptive motor control. More information is available at her lab website.
A central quest in neuroscience is the neural origin of behavior. As our ability to record large neural and behavioral data increases, there is growing interest in modeling neural dynamics during adaptive behaviors to probe neural representations. Yet, we are still limited in both the number of neurons and length of time we can record from behaving animals in a session. Therefore, we need new methods that can combine data across animals and sessions with minimal assumptions, and generate interpretable neural embedding spaces. Moreover, we need tools to measure behavior robustly. In my talk I will discuss how we approach understanding neural dynamics during sensorimotor learning by developing deep learning tools for behavioral and neural analysis. While these tools apply to a broad range of systems–from cheetahs to mice, spikes to calcium–I will highlight our ongoing work on adaptive motor control in mice.
Transcriptomics has revealed the exquisite diversity of cortical inhibitory neurons, but it is not known whether these fine molecular subtypes have correspondingly diverse activity patterns in the living brain. Here, we show that inhibitory subtypes in primary visual cortex (V1) have diverse correlates with brain state, but that this diversity is organized by a single factor: position along their main axis of transcriptomic variation. We combined in vivo 2-photon calcium imaging of mouse V1 with a novel transcriptomic method to identify mRNAs for 72 selected genes in ex vivo slices. We used previously-defined transcriptomic clusters (Tasic et al, Nature 2018) to classify inhibitory neurons imaged in layers 1-3 into a three-level hierarchy of 5 Families, 11 Types, and 35 Subtypes. Visual responses differed significantly only across Families, with the Sncg Family showing notable suppression by visual stimuli. Modulation by brain state differed at all hierarchical levels, but a cell type’s brain state modulation and correlations with simultaneously recorded cells could be largely predicted from a single transcriptomic axis, the first transcriptomic principal component. Inhibitory Subtypes that fired more in resting, oscillatory brain states had narrower spikes, lower input resistance, weaker adaptation, and less axon in layer 1 as determined in vitro (Gouwens et al Cell 2020); Subtypes firing more during arousal had the opposite properties. The former Subtypes express more inhibitory cholinergic receptors, and the latter more excitatory cholinergic receptors in single-cell data. Thus, a simple principle may largely explain how diverse inhibitory V1 Subtypes shape state-dependent cortical processing.
Kenneth D. Harris studied mathematics at Cambridge University, did a PhD in robotics at UCL, then moved to Rutgers University in the United States for postdoctoral work in neuroscience. Before returning to UCL in 2012, he was Associate Professor of Neuroscience at Rutgers, and Professor of Neurotechnology at Imperial College London. He is currently Professor of Quantitative Neuroscience in the UCL Institute of Neurology. Together with Matteo Carandini he directs the Cortexlab.
Dr. Addy’s research focuses on the neurobiological processes underlying substance use disorders, mood disorders, and comorbid substance use and mood disorders. Dr. Addy’s team uses multiple methodologies, including behavioral paradigms such as intravenous drug self-administration, acute and chronic stress paradigms, and anxiety and amotivation paradigms, along with integrated pharmacological, in vivo electrochemical, and in vivo optogenetic methods to investigate these mechanisms. Dr. Addy will present his preclinical findings, revealing cholinergic and L-type calcium channel processes in the mesolimbic dopamine reward system that robustly mediate substance use and mood disorder behavioral phenotypes through regulation of dopaminergic activity. Dr. Addy will also describe ongoing work with potential therapeutic compounds, targeting subtype-specific muscarinic receptors and L-type calcium channels. Finally, he will describe upcoming clinical collaborative studies, based on his team’s recent preclinical findings.
Nii Addy is the Albert E. Kent Professor of Psychiatry and an Associate Professor of Cellular and Molecular Physiology at the Yale School of Medicine. Dr. Addy is also the inaugural Director of Scientist Diversity and Inclusion at the Yale School of Medicine, focusing on supporting the faculty development of basic scientists from underrepresented groups at the School of Medicine. In addition to his campus work, Dr. Addy hosts the Addy Hour podcast, discussing topics at the intersection of neuroscience, mental health, faith, culture and social justice. More information is available at his lab website.
10.25.2023 | 9:00AM-10:00AM
11.11.2023 - 11.15.2023 | 9:00AM