Seminars

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.

The coupled hydrology and ice dynamics of the higher elevations of the Greenland Ice Sheet, where ice is beyond a kilometre thick, remains poorly understood. This lack of knowledge is a significant source of uncertainty in the models used to project the ice sheet’s sea level rise contribution, both in terms of surface mass balance and the potential for dynamic drawdown. I will discuss some of our recent and ongoing work towards (1) improving the accuracy of partitioning between refreezing and runoff processes, and (2) capturing the impact of surface meltwater on ice sliding where the ice sheet is more than a kilometre thick.

Optical imaging is a major research tool in the basic sciences, and is the only imaging modality that routinely enables non-ionized imaging with subcellular spatial resolutions and high imaging speeds. In biological imaging applications, however, optical imaging is limited by tissue scattering to short imaging depths. This prevents large-scale bio-imaging by allowing visualization of only the outer superficial layers of an organism, or specific components isolated from within the organism and prepared in-vitro.

Research articles and laboratory protocol organization often lack detailed instructions for replicating experiments. protocols.io is an open-access platform where researchers collaboratively create dynamic, interactive, step-by-step protocols that can be executed on mobile devices or the web. Researchers can easily and efficiently share protocols with colleagues, collaborators, the scientific community, or make them public. Real-time communication and interaction keep protocols up to date. Public protocols receive a DOI and enable open communication with authors and researchers to foster efficient experimentation and reproducibility.

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.

Thalamic networks, at the core of thalamocortical and thalamosubcortical communications, underlie processes of perception, attention, memory, emotions, and the sleep-wake cycle, and are disrupted in mental disorders, including schizophrenia and autism. However, the underlying mechanisms of pathology are unknown. I will present novel evidence on key organizational principles, structural, and molecular features of thalamocortical networks, as well as critical thalamic pathway interactions that are likely affected in disorders. This data can facilitate modeling typical and abnormal brain function and can provide the foundation to understand heterogeneous disruption of these networks in sleep disorders, attention deficits, and cognitive and affective impairments in schizophrenia and autism, with important implications for the design of targeted therapeutic interventions

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.

The cortex comprises many neuronal types, which can be distinguished by their transcriptomes: the sets of genes they express. Little is known about the in vivo activity of these cell types, particularly as regards the structure of their spike trains, which might provide clues to cortical circuit function. To address this question, we used Neuropixels electrodes to record layer 5 excitatory populations in mouse V1, then transcriptomically identified the recorded cell types. To do so, we performed a subsequent recording of the same cells using 2-photon (2p) calcium imaging, identifying neurons between the two recording modalities by fingerprinting their responses to a “zebra noise” stimulus and estimating the path of the electrode through the 2p stack with a probabilistic method. We then cut brain slices and performed in situ transcriptomics to localize ~300 genes using coppaFISH3d, a new open source method, and aligned the transcriptomic data to the 2p stack. Analysis of the data is ongoing, and suggests substantial differences in spike time coordination between ET and IT neurons, as well as between transcriptomic subtypes of both these excitatory types.