Neuroscience seminars

In April, we will host Nolan Williams and Mustafa Husain. Be prepared to embark on a journey from early brain stimulation with ECT to state-of-the art TMS protocols and magnetic seizure therapy! The talks will be held on Thursday, April 25th at noon ET / 6PM CET. Nolan Williams, MD, is an associate professor of Psychiatry and Behavioral Science at Stanford University. He developed the SAINT protocol, which is the first FDA-cleared non-invasive, rapid-acting neuromodulation treatment for treatment-resistant depression. Mustafa Husain, MD, is an adjunct professor of Psychiatry and Behavioral Sciences at Duke University and a professor of Psychiatry and Neurology at UT Southwestern Medical Center, Dallas. He will tell us about “Evolution of convulsive therapy from electroconvulsive therapy to Magnetic Seizure Therapy”. As always, we will also get a glimpse at the “Person behind the science”. Please register va talks.stimulatingbrains.org to receive the (free) Zoom link, subscribe to our newsletter, or follow us on Twitter/X for further updates!

How do cortical circuits acquire new dynamics that drive learned movements? This webinar will focus on mouse premotor cortex in relation to learned lick-timing and explore high-density electrophysiology using our silicon neural probes alongside region and cell-type-specific acute genetic manipulations of proteins required for synaptic plasticity.

Neural computation is inextricably bound to decisions that must be made under time pressure and uncertainty. At the level of neural circuits, single neurons need to decide whether to spike. On longer timescales, the component circuitry needs to decide whether to reconfigure to store memories and adapt to novel situations. In this talk I will focus on two fun ideas in each of these contexts by showing how nonlinearities in neural components naturally form excitable switches that enable reliable decisions to be made in fluctuating environments. I will also issue propaganda that the kind of high level, cognitive faculties that we normally associate with decision making apply equally well and are understudied at the level of neural and synaptic populations. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2024-04-17. Recording duration: 00:41:08.

The basis of the mind, of mental states, and complex behaviors is the flow of energy through microscopic and macroscopic brain structures. Energy flow through brain circuits is powered by thousands of mitochondria populating the inside of every neuron, glial, and other nucleated cell across the brain-body unit. This seminar will cover emerging approaches to study the mind-mitochondria connection and present early attempts to map the distribution and diversity of mitochondria across brain tissue. In rodents, I will present convergent multimodal evidence anchored in enzyme activities, gene expression, and animal behavior that distinct behaviorally-relevant mitochondrial phenotypes exist across large-scale mouse brain networks. Extending these findings to the human brain, I will present a developing systematic biochemical and molecular map of mitochondrial variation across cortical and subcortical brain structures, representing a foundation to understand the origin of complex energy patterns that give rise to the human mind.

There is a fundamental tension between storing discrete traces of individual experiences, which allows recall of particular moments in our past without interference, and extracting regularities across these experiences, which supports generalization and prediction in similar situations in the future. One influential proposal for how the brain resolves this tension is that it separates the processes anatomically into Complementary Learning Systems, with the hippocampus rapidly encoding individual episodes and the neocortex slowly extracting regularities over days, months, and years. But this does not explain our ability to learn and generalize from new regularities in our environment quickly, often within minutes. We have put forward a neural network model of the hippocampus that suggests that the hippocampus itself may contain complementary learning systems, with one pathway specializing in the rapid learning of regularities and a separate pathway handling the region’s classic episodic memory functions. This proposal has broad implications for how we learn and represent novel information of specific and generalized types, which we test across statistical learning, inference, and category learning paradigms. We also explore how this system interacts with slower-learning neocortical memory systems, with empirical and modeling investigations into how the hippocampus shapes neocortical representations during sleep. Together, the work helps us understand how structured information in our environment is initially encoded and how it then transforms over time.

The epileptogenesis process is associated with large-scale changes in gene expression, which contribute to the remodelling of brain networks permanently altering excitability. About 80% of the protein coding genes are under the influence of the circadian rhythms. These are 24-hour endogenous rhythms that determine a large number of daily changes in physiology and behavior in our bodies. In the brain, the master clock regulates a large number of pathways that are important during epileptogenesis and established-epilepsy, such as neurotransmission, synaptic homeostasis, inflammation, blood-brain barrier among others. In-depth mapping of the molecular basis of circadian timing in the brain is key for a complete understanding of the cellular and molecular events connecting genes to phenotypes.

Inhibition has long been thought to stabilize the activity of cortical networks at low rates, and to shape significantly their response to sensory inputs. In this talk, I will describe three recent collaborative projects that shed light on these issues. (1) I will show how optogenetic excitation of inhibition neurons is consistent with cortex being inhibition stabilized even in the absence of sensory inputs, and how this data can constrain the coupling strengths of E-I cortical network models. (2) Recent analysis of the effects of optogenetic excitation of pyramidal cells in V1 of mice and monkeys shows that in some cases this optogenetic input reshuffles the firing rates of neurons of the network, leaving the distribution of rates unaffected. I will show how this surprising effect can be reproduced in sufficiently strongly coupled E-I networks. (3) Another puzzle has been to understand the respective roles of different inhibitory subtypes in network stabilization. Recent data reveal a novel, state dependent, paradoxical effect of weakening AMPAR mediated synaptic currents onto SST cells. Mathematical analysis of a network model with multiple inhibitory cell types shows that this effect tells us in which conditions SST cells are required for network stabilization.

In March we will focus on TMS and host Ghazaleh Soleimani and Colleen Hanlon. The talks will talk place on Thursday, March 28th at noon ET – please be aware that this means 5PM CET since Boston already switched to summer time! Ghazaleh Soleimani, PhD, is a postdoctoral fellow in Dr Hamed Ekhtiari’s lab at the University of Minnesota. She is also the executive director of the International Network of tES/TMS for Addiction Medicine (INTAM). She will discuss “Adapting to diversity: Integrating variability in brain structure and function into personalized / closed-loop non-invasive brain stimulation for substance use disorders”. Colleen Hanlon, PhD, currently serves as a Vice President of Medical Affairs for BrainsWay, a company specializing in medical devices for mental health, including TMS. Colleen previously worked at the Medical University of South Carolina and Wake Forest School of Medicine. She received the International Brain Stimulation Early Career Award in 2023. She will discuss “Currents of Hope: how noninvasive brain stimulation is reshaping modern psychiatric care”. As always, we will also get a glimpse at the “Person behind the science”. Please register va talks.stimulatingbrains.org to receive the (free) Zoom link, subscribe to our newsletter, or follow us on Twitter/X for further updates!

The visual system faces a dual challenge. On the one hand, features of the natural visual environment should be stably processed - irrespective of ongoing wiring changes, representational drift, and behavior. On the other hand, eye, head, and body motion require a robust integration of pose and gaze shifts in visual computations for a stable perception of the world. We address these dimensions of stable visual processing by studying the circuit mechanism of long-term representational stability, focusing on the role of plasticity, network structure, experience, and behavioral state while recording large-scale neuronal activity with miniature two-photon microscopy.

Immune-mediated mechanisms are increasingly recognised as a cause of epilepsy even in the absence of an immune response against a specifical neuronal antigen. In some cases, these autoimmune processes are clearly pathogenic, for example acute seizures in autoimmune encephalitis, whereas in others this is less clear, for example autoimmune-associated epilepsy. Recent research has provided novel insights into the clinical, paraclinical and immunopathogenetic mechanisms in these conditions. I will provide an overview of clinical and paraclinical features of immune-associated seizures. Furthermore, I will describe specific immunopathogenic examples implicating lymphoid follicular autoimmunisation and intrathecal B cells in these conditions. These insights into immunopathogenesis may help to explain the role of current and immunotherapies in these conditions.

In the last of this year’s Brain Prize webinars, Elizabeth Pollina (Washington University, USA), Eric Nestler (Icahn School of Medicine Mount Sinai, USA) and Michelle Monje (Stanford University, USA) will present their work on activity-dependent gene regulation in health and disease. Each speaker will present for 25 minutes, and the webinar will conclude with an open discussion. The webinar will be moderated by the winners of the 2023 Brain Prize, Michael Greenberg, Erin Schuman and Christine Holt.