Seminars

Over the past decade our community has made substantial progress in the construction of anatomically detailed network models of the cortical tissue. Thanks to advances in computer hardware and simulation technology, researchers can now routinely work with these models at the natural density of neurons and synapses. Moreover, the availability of cloud services means that such investigations can be carried out without having to install either the model or the simulation software. A recent workshop analyzed the impact of a specific model of the cortical microcircuit, published ten years ago . The model has been reused in multiple contexts: for reproduction studies, validation of mean-field approaches, exploration of methods of model sharing, and as a building block for larger models. Although the model was less successful in inspiring further neuroscientific studies than the authors of the original work had hoped, it became a de facto benchmark for neuromorphic computing systems. It sparked a constructive race for ever shorter simulation times and lower energy consumption. The quantitative comparison of different platforms reveals qualitative differences between conventional and neuromorphic hardware and limits of speed-up. The structure of the model is based on light microscopy because these were the data available at the time. Guided by simulation results and physiological evidence, the original publication hypothesized a preference of excitatory neurons for inhibitory targets. Modern electron microscopy data of cortical volumes combined with AI based reconstruction techniques is capable of resolving individual synaptic connections. This advances the concept of digital twins of the cortical network to a new level of precision, and has already enabled us to confirm the assumption of target type specifity underlying earlier models. Maybe with the progress sketched here, our community is at a transition point where it becomes easier to cooperatively and incrementally work on models with a larger explanatory scope. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2025-12-10. Recording duration: 00:39:15.

The Nature versus Nurture 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.

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 rapidly learn 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 hippocampal replay 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. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2025-12-03. Recording duration: 00:53:05.

Recurrent networks with balanced excitation-inhibition explain a wide range of neurophysiological observations, but can only implement a limited set of transformations on their input. On the other hand networks of firing-rate units with low-rank connectivity have universal computational capabilities, but do not work with spikes or generate noise self-consistently. Although empirical approaches to merge these two computational frameworks have been constructed, there is no established theory describing their unification. Here we develop such a theory. We study analytically and numerically networks with connectivity comprising random “strong”, and low-rank “weak” components. When the low-rank connectivity is slow, a well-defined notion of instantaneous firing rate emerges which implies universal computation as previously shown. However, the fact that such time-varying rates are the result of E-I balance has important implications. We show that internally or externally generated fluctuations along particular latent modes tend to break the E-I balance. Its maintenance is obtained through the emergence of a spontaneous coupling between the mean and the variance of the membrane potential and the norm of the latent state driving these modes. This leads to several predictions, the most counterintuitive of which is that coherent global fluctuations in subthreshold membrane potential (Vm) should coexist with desynchronized activity at constant firing rates when the dynamics of these modes is excited. To test our theory, we show that the coupling between the average Vm and the latent state adds new non-linear dimensions to the low-dimensional manifold of the network, which lead to a frequency doubling when the input to the network is periodic, a prediction that is borne out in population recordings from mouse V1. Our results unify two prevalent frameworks for cortical computation and clarify the relationship between computation, dynamics and geometry in circuits of spiking neurons. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2025-11-26. Recording duration: 00:39:26.

Accurate perception of the environment is a constructive process that requires integration of external bottom-up sensory signals with internally-generated top-down information reflecting past experiences and current aims. Decades of work have elucidated how sensory neocortex processes physical stimulus features. In contrast, examining how memory-related-top-down information is encoded and integrated with bottom-up signals has long been challenging. Here, I will discuss our recent work pinpointing the outermost layer 1 of neocortex as a central hotspot for processing of experience-dependent top-down information threat during perception, one of the most fundamentally important forms of sensation.

Minimising cortical prediction errors is thought to be a key computation underlying perception, action, and learning. Yet, how the cortex represents and uses uncertainty in this process remains unclear. In the first part of this talk, I will present a normative framework showing how uncertainty can modulate prediction error activity to yield uncertainty-modulated prediction errors (UPEs), hypothesised to be represented by layer 2/3 pyramidal neurons. We propose that these UPEs are computed through inhibitory mechanisms involving SST and PV interneurons. A circuit model demonstrates how cortical cell types can locally compute means, variances, and UPEs, leading to adaptive learning rates. In the second part, I will discuss how uncertainty modulation could be controlled by higher-level representations. We formally derived neural dynamics that minimise prediction errors under the assumption that cortical areas must not only predict the activity in other areas and sensory streams but also jointly project their inverse expected uncertainty about their predictions, which we call “confidence”. This yields a confidence-weighted integration of bottom-up and top-down signals, consistent with Bayesian principles, and predicts the existence of second-order errors that compare confidence with performance. We predict that these second-order errors propagate alongside classical prediction errors through the cortical hierarchy, and simulations demonstrate that this mechanism enables nonlinear classification within a single cortical area. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2025-11-12. Recording duration: 00:29:21.

Assessing how brain activity generalizes across individuals is a central challenge in experimental neuroscience. Traditional task- or stimulus-driven approaches align data through trial averaging and anatomical registration, but these methods fail for spontaneous activity, where no shared temporal reference exists. In this talk, I will introduce a statistical framework, called latent-aligned Restricted Boltzmann Machines, to build a common representational space from whole-brain recordings of spontaneous activity in multiple zebrafish larvae. This shared latent space, composed of spatially localized co-activation motifs or cell assemblies, allows bidirectional mapping of brain states: activity patterns from one fish can be encoded and decoded into another. The translated activity patterns retain their original spatial structure and show high plausibility within the recipient brain. We further use this shared space to segment spontaneous activity into discrete brain states and we quantify their Markovian transition statistics. Remarkably, these state-to-state dynamics are stereotyped across individuals, suggesting that spontaneous activity reflects intrinsic computational priors of neural processing. Together, these results demonstrate how probabilistic generative modeling can bridge individual variability and reveal conserved organizational principles of vertebrate brains. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2025-11-05. Recording duration: 00:36:37.

This talk aims to answer these questions along four dimensions. First is history. RL was the basis of AI long before the term AI was introduced in 1956. The first machine learning (ML) systems were based on RL even before digital computers existed. Despite notable early successes of ML based on RL, RL essentially disappeared from ML until relatively recently. A second reason for renewed interest in RL is the clarification of some misunderstandings that have been prevalent in the ML community. A third, and most important, reason for this resurgence is that new, or rediscovered, algorithms and connections to well developed mathematical and engineering methods have been worked out. Finally, a fourth reason for the renewed interest in RL is its strong links to animal reward systems, in particular, to the role that dopamine plays in motivation and learning. VVTNS Sixth Season Opening Lecture. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2025-10-29. Recording duration: 00:55:21.

Cellular crosstalk is an essential process during brain development and is influenced by numerous factors, including cell morphology, adhesion, the local extracellular matrix and secreted vesicles. Inspired by mutations associated with neurodevelopmental disorders, we focus on understanding the role of extracellular mechanisms essential for the proper development of the human brain. Therefore, we combine 2D and 3D in vitro human models to better understand the molecular and cellular mechanisms involved in progenitor proliferation and fate, migration and maturation of excitatory and inhibitory neurons during human brain development and tackle the causes of neurodevelopmental disorders.

Neuroplasticity is essential for the establishment and strengthening of neural circuits. Repetitive transcranial magnetic stimulation (rTMS) is commonly used to modulate cortical excitability and shows promise in the treatment of some neurological disorders. Low intensity magnetic stimulation (LI-rTMS), which does not directly elicit action potentials in the stimulated neurons, have also shown some therapeutic effects, and it is important to determine the biological mechanisms underlying the effects of these low intensity magnetic fields, such as would occur in the regions surrounding the central high-intensity focus of rTMS. Our team has used a focal low-intensity (10mT) magnetic stimulation approach to address some of these questions and to identify cellular mechanisms. I will present several studies from our laboratory, addressing (1) effects of LIrTMS on neuronal activity and excitability ; and (2) neuronal morphology and post-lesion repair. The ensemble of our results indicate that the effects of LI-rTMS depend upon the stimulation pattern, the age of the animal, and the presence of cellular magnetoreceptors.

A combinatorial neural code for long-term motor memory