Neuroscience seminars

We continuously detect sensory data, like sights and sounds, and use this information to guide our behaviour. However, rather than relying on single sensory channels, which are noisy and can be ambiguous alone, we merge information across our senses and leverage this combined signal. In biological networks, this process (multisensory integration) is implemented by multimodal neurons which are often thought to receive the information accumulated by unimodal areas, and to fuse this across channels; an algorithm we term accumulate-then-fuse. However, it remains an open question how well this theory generalises beyond the classical tasks used to test multimodal integration. Here, we explore this by developing novel multimodal tasks and deploying probabilistic, artificial and spiking neural network models. Using these models we demonstrate that multimodal units are not necessary for accuracy or balancing speed/accuracy in classical multimodal tasks, but are critical in a novel set of tasks in which we comodulate signals across channels. We show that these comodulation tasks require multimodal units to implement an alternative fuse-then-accumulate algorithm, which excels in naturalistic settings and is optimal for a wide class of multimodal problems. Finally, we link our findings to experimental results at multiple levels; from single neurons to behaviour. Ultimately, our work suggests that multimodal neurons may fuse-then-accumulate evidence across channels, and provides novel tasks and models for exploring this in biological systems. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2023-10-25. Recording duration: 00:30:13.

Microglia are the resident CNS macrophages of the brain parenchyma. They have many and opposing roles in health and disease, ranging from inflammatory to anti-inflammatory and protective functions, depending on the developmental stage and the disease context. In Multiple Sclerosis, microglia are involved to important hallmarks of the disease, such as inflammation, demyelination, axonal damage and remyelination, however the exact mechanisms controlling their transformation towards a protective or devastating phenotype during the disease progression remains largely unknown until now. We wish to understand how brain microglia respond to demyelinating insults and how their behaviour changes in recovery. To do so we developed a novel histopathological analysis approach in 3D and a cell-based analysis tool that when applied in the cuprizone model of demyelination revealed region- and disease- dependent changes in microglial dynamics in the brain grey matter during demyelination and remyelination. We now use similar approaches with the aim to unravel sensitive changes in microglial dynamics during neuroinflammation in the EAE model. Furthermore, we employ constitutive knockout and tamoxifen-inducible gene-targeting approaches, immunological techniques, genetics and bioinformatics and currently seek to clarify the specific role of the brain resident microglial NF-κB molecular pathway versus other tissue macrophages in EAE.

With this webinar series, the ALBA Disability & Accessibility Working Group aims to bring down the ivory tower of ableism among the brain research community, one extraordinary neuroscientist at a time. These webinars give a platform to scientists with disabilities across the globe and neuroscience disciplines, while reflecting on how to promote inclusive working environments and accessibility to research. For this 3rd episode, Dr. Donna Rose Addis (Rotman Research Institute, Baycrest & University of Toronto, Canada) will talk about her research and experience.

When interacting with complex environments, humans can rapidly adapt their behavior to changes in task or context. To facilitate this adaptation, we often spend substantial periods of time contemplating possible futures before acting. For such planning to be rational, the benefits of planning to future behavior must at least compensate for the time spent thinking. Here we capture these features of human behavior by developing a neural network model where not only actions, but also planning, are controlled by prefrontal cortex. This model consists of a meta-reinforcement learning agent augmented with the ability to plan by sampling imagined action sequences drawn from its own policy, which we refer to as `rollouts'. Our results demonstrate that this agent learns to plan when planning is beneficial, explaining the empirical variability in human thinking times. Additionally, the patterns of policy rollouts employed by the artificial agent closely resemble patterns of rodent hippocampal replays recently recorded in a spatial navigation task, in terms of both their spatial statistics and their relationship to subsequent behavior. Our work provides a new theory of how the brain could implement planning through prefrontal-hippocampal interactions, where hippocampal replays are triggered by -- and in turn adaptively affect -- prefrontal dynamics.

The human voice is possibly the most important sound category in the social landscape. Compared to other non-verbal emotion signals, the voice is particularly effective in communicating emotions: it can carry information over large distances and independent of sight. However, the study of vocal emotion expression and perception is surprisingly far less developed than the study of emotion in faces. Thereby, its neural and functional correlates remain elusive. As the voice represents a dynamically changing auditory stimulus, temporally sensitive techniques such as the EEG are particularly informative. In this talk, the dynamic neurocognitive operations that take place when we listen to vocal emotions will be specified, with a focus on the effects of stimulus type, task demands, and speaker and listener characteristics (e.g., age). These studies suggest that emotional voice perception is not only a matter of how one speaks but also of who speaks and who listens. Implications of these findings for the understanding of psychiatric disorders such as schizophrenia will be discussed.

The advent of next generation sequencing ushered in a ten-year period of exuberant technology development, enabling the quantification of gene expression and epigenetic features within individual cells, and within intact tissue sections. In this seminar, I will outline our technological contributions, beginning with the development of Drop-seq, a method for high-throughput single cell analysis, followed by the development of Slide-seq, a technique for measuring genome-wide expression at 10 micron spatial resolution. Using a combination of these techniques, we recently constructed a comprehensive cell type atlas of the adult mouse brain, positioning cell types within individual brain structures. I will discuss the major findings from this dataset, including emerging principles of neurotransmission, and the localization of disease gene signatures to specific cell types. Finally, I will introduce a new spatial technology, Slide-tags, that unifies single cell and spatial genomics into a single, highly scalable assay.

Sleep and epilepsy are tightly interconnected: On the one hand disturbed sleep is known to negatively affect epilepsy, whereas on the other hand epilepsy negatively impacts sleep. In this talk, we leverage on the unique opportunity provided by simultaneous stereo-EEG and sleep recordings to disentangle these relationships. We will discuss latest evidence on if anatomy (temporal vs. extratemporal), time (early vs. late sleep), and type of epileptic activity (ictal vs. interictal) influence how epileptic activity is modulated by sleep. After this talk, attendees will have a more nuanced understanding of the contributions of location, time and type of epileptic activity in the relationship between sleep and epilepsy.

Much as Santiago Ramón y Cajal is the godfather of neuronal computation, which occurs among neurons that communicate predominantly via threshold logic, Camillo Golgi is the inadvertent godfather of neurovascular signaling, in which the endothelial cells that form the lumen of blood vessels communicate via electrodiffusion as well as threshold logic. I will address questions that define spatiotemporal patterns of constriction and dilation that develop across the network of cortical vasculature: First - is there a common topology and geometry of brain vasculature (our work)? Second - what mechanisms govern neuron-to-vessel and vessel-to-vessel signaling (work of Mark Nelson at U Vermont)? Last - what is the nature of competition among arteriole smooth muscle oscillators and the underlying neuronal drive (our work)? This answers to these questions bear on fundamental aspects of brain science as well as practical issues, including the relation of fMRI signals to neuronal activity and the impact of vascular dysfunction on cognition. Challenges and opportunities for experimentalists and theorists alike will be discussed. The organizer explicitly announced an exceptional 11:15 am ET start. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2023-10-11. Recording duration: 00:56:46.

Detecting the direction of image motion is important for visual navigation, predator avoidance and prey capture, and thus essential for the survival of all animals that have eyes. However, the direction of motion is not explicitly represented at the level of the photoreceptors: it rather needs to be computed by subsequent neural circuits, involving a comparison of the signals from neighboring photoreceptors over time. The exact nature of this process represents a classic example of neural computation and has been a longstanding question in the field. Much progress has been made in recent years in the fruit fly Drosophila melanogaster by genetically targeting individual neuron types to block, activate or record from them. Our results obtained this way demonstrate that the local direction of motion is computed in two parallel ON and OFF pathways. Within each pathway, a retinotopic array of four direction-selective T4 (ON) and T5 (OFF) cells represents the four Cartesian components of local motion vectors (leftward, rightward, upward, downward). Since none of the presynaptic neurons is directionally selective, direction selectivity first emerges within T4 and T5 cells. Our present research focuses on the cellular and biophysical mechanisms by which the direction of image motion is computed in these neurons.

The neurobiological mechanisms of arousal and anesthesia remain poorly understood. Recent evidence highlights the key role of interactions between the cerebral cortex and the diffusely projecting matrix thalamic nuclei. Here, we interrogate these processes in a whole-brain corticothalamic neural mass model endowed with targeted and diffusely projecting thalamocortical nuclei inferred from empirical data. This model captures key features seen in propofol anesthesia, including diminished network integration, lowered state diversity, impaired susceptibility to perturbation, and decreased corticocortical coherence. Collectively, these signatures reflect a suppression of information transfer across the cerebral cortex. We recover these signatures of conscious arousal by selectively stimulating the matrix thalamus, recapitulating empirical results in macaque, as well as wake-like information processing states that reflect the thalamic modulation of largescale cortical attractor dynamics. Our results highlight the role of matrix thalamocortical projections in shaping many features of complex cortical dynamics to facilitate the unique communication states supporting conscious awareness.

It’s our pleasure to announce that we will host Haidar Dafsari and Günther Deuschl on September 28th at noon ET / 6PM CET. Haidar Dafsari, MD, is a researcher and lecturer at the University Hospital Cologne. Günther Deuschl, MD, PhD, is a professor at Kiel University. He was president of the International Movement Disorders Society (MDS) from 2011-2013, Editor in Chief of the journal Movement Disorders and has been awarded numerous high-class awards. Beside his scientific presentation, he will give us a glimpse at the “Person behind the science”.The talks will be followed by a shared discussion. You can register via talks.stimulatingbrains.org to receive the (free) Zoom link!

To form a coherent perception of the world around us, we are constantly processing and integrating sensory information from multiple modalities. In fact, when auditory and visual stimuli occur within ~100 ms of each other, individuals tend to perceive the stimuli as a single event, even though they occurred separately. In recent years, our lab, and others, have developed rat models of audiovisual temporal perception using behavioural tasks such as temporal order judgments (TOJs) and synchrony judgments (SJs). While these rodent models demonstrate metrics that are consistent with humans (e.g., perceived simultaneity, temporal acuity), we have sought to confirm whether rodents demonstrate the hallmarks of audiovisual temporal perception, such as predictable shifts in their perception based on experience and sensitivity to alterations in neurochemistry. Ultimately, our findings indicate that rats serve as an excellent model to study the neural mechanisms underlying audiovisual temporal perception, which to date remains relativity unknown. Using our validated translational audiovisual behavioural tasks, in combination with optogenetics, neuropharmacology and in vivo electrophysiology, we aim to uncover the mechanisms by which inhibitory neurotransmission and top-down circuits finely control ones’ perception. This research will significantly advance our understanding of the neuronal circuitry underlying audiovisual temporal perception, and will be the first to establish the role of interneurons in regulating the synchronized neural activity that is thought to contribute to the precise binding of audiovisual stimuli.

Humans and other animals evolved in habitats fraught with a range of environmental challenges to their bodies and brains. Accordingly, cells and organ systems possess adaptive stress-responsive signaling pathways that enable them to not only withstand environmental challenges, but also to prepare for future challenges and function more efficiently. These phylogenetically conserved processes are the foundation of the hormesis principle in which repeated exposures to low to moderate amounts of an environmental challenge improve cellular and organismal fitness. Here I describe cellular and molecular mechanisms by which cells in the brain and body respond to intermittent fasting and exercise in ways that enhance performance and counteract aging and disease processes. Switching back and forth between adaptive stress response (during fasting and exercise) and growth and plasticity (eating, resting, sleeping) modes enhances the performance and resilience of various organ systems. While pharmacological interventions that engage a particular hormetic mechanism are being developed, it seems unlikely that any will prove superior to fasting and exercise.

Dr. Pasinetti is the Saunders Family Chair and Professor of Neurology at Icahn School of medicine at Mount Sinai, New York. His studies allowed him to develop novel therapeutic approaches through investigation of preventable risk factors including mood disorders in the promotion of resilience against neurodegenerative disorder. In his presentation Dr. Pasinetti will discuss novel concepts about the gut-brain axis in mechanisms associated to peripheral adaptive immunity as therapeutic targets to mitigate the onset and the progression of Alzheimer’s disease and other form of dementia.

Founded in 2002, the Brain Connectivity Workshop (BCW) is an annual international meeting for in-depth discussions of all aspects of brain connectivity research. By bringing together experts in computational neuroscience, neuroscience methodology and experimental neuroscience, it aims to improve the understanding of the relationship between anatomical connectivity, brain dynamics and cognitive function. These workshops have a unique format, featuring only short presentations followed by intense discussion. This year’s workshop is co-organised by Wellcome, putting the spotlight on brain connectivity in mental health disorders. We look forward to having you join us for this exciting, thought-provoking and inclusive event.