Seminars

Computations in neural circuits are often construed as being implemented through the coordinated dynamics of neurons. In this picture, the role of synaptic connectivity is to sculpt neuronal dynamics to implement computations of interest. Of course, synapses are not static but change on a variety of timescales, including fast timescales comparable to those of neurons. Thus, a more accurate view of computation in neural circuits may involve the coupled dynamics of neurons and synapses. This form of computation is closer to what is implemented by Transformers via an equivalence between ongoing synaptic plasticity and self-attention. I will first describe a nonlinear recurrent neural-network model with ongoing Hebbian dynamics of “fast” synapses atop unstructured “slow” synapses. I will then describe two computations implemented through neuronal-synaptic dynamics, which can be studied in this model using techniques including dynamical mean-field theory and random-matrix theory. First, there exists a novel phase termed “freezable chaos” in which a stable fixed point of neuronal dynamics is continuously destabilized by synaptic dynamics. This allows for the creation of a stable fixed point at any neuronal state visited by the network by halting synaptic plasticity. Second, I will describe an effect termed “persistent oscillations” in which, following stimulation by a periodic signal, a plastic network continues to autonomously reproduce a similar signal for a duration exceeding any intrinsic timescale in the system. Thus, ongoing Hebbian plasticity can provide a dynamic form of working memory, complementing the static form provided by freezable chaos. Ongoing experimental work suggests that this effect is realized in cortical organoids. Overall, this line of work suggests that synapses should be promoted to first-class dynamical degrees of freedom in our conceptual understanding of neural-circuit function. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2026-01-14. Recording duration: 00:43:14.

Neural activity is often analyzed with respect to external referents, such as the onset of a sensory stimulus or an overt motor action. Simultaneous recordings allow referencing neurons’ activity to each other and thus detecting signals that are internal to the organism. Further, multi-region simultaneous recordings allow observing how these internal signals are coordinated across the brain. Following this logic in rats performing a perceptual decision-making task, we recorded simultaneously from thousands of neurons across up to 20 brain regions at once. Here we report two internal signals which we found to profoundly shape decision-related neural dynamics and brain states. First, we decoded the continuously evolving decision state separately from each region, and found surprisingly large magnitude co-fluctuations in these measures. Dimensionality analysis showed these to be dominated by a single state variable, suggesting that only a single decision-making computation, not multiple parallel computations, are being carried out during the analyzed period. Second, we found that the precise time the subject commits to a decision – a covert event that we decoded from large-scale neural activity in primary motor cortex – was accompanied by a coordinated change, across the brain, from a decision formation to a post-commitment state. The two states differ substantially in their choice-predictive neural dynamics and in their inter-region correlations. Therefore, knowing the time of this state change on single trials is needed to correctly parse fundamentally different phases of decision-making. Overall, our data suggest that internally-referenced signals and state changes, not timelocked to external events but detectable through simultaneous recordings, are major features of neural activity during cognition. VVTNS 2026 Opening Lecture. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2026-01-07. Recording duration: 00:42:45.

Traditionally, touch is associated with exteroception and is rarely considered a relevant sensory cue for controlling movements in space, unlike vision. We developed a technique to isolate and measure tactile involvement in controlling sliding finger movements over a surface. Young adults traced a 2D shape with their index finger under direct or mirror-reversed visual feedback to create a conflict between visual and somatosensory inputs. In this context, increased reliance on somatosensory input compromises movement accuracy. Based on the hypothesis that tactile cues contribute to guiding hand movements when in contact with a surface, we predicted poorer performance when the participants traced with their bare finger compared to when their tactile sensation was dampened by a smooth, rigid finger splint. The results supported this prediction. EEG source analyses revealed smaller current in the source-localized somatosensory cortex during sensory conflict when the finger directly touched the surface. This finding supports the hypothesis that, in response to mirror-reversed visual feedback, the central nervous system selectively gated task-irrelevant somatosensory inputs, thereby mitigating, though not entirely resolving, the visuo-somatosensory conflict. Together, our results emphasize touch’s involvement in movement control over a surface, challenging the notion that vision predominantly governs goal-directed hand or finger movements.

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.

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

Connectomic traces of Hebbian plasticity in the entorhinalhippocampal system

Different brain cell types exhibit distinct metabolic signatures that link energy economy to cellular function. Astrocytes and neurons, for instance, diverge dramatically in their reliance on glycolysis versus oxidative phosphorylation, underscoring that metabolic fuel efficiency is not uniform across cell types. A key factor shaping this divergence is the structural organization of the mitochondrial respiratory chain into supercomplexes. Specifically, complexes I (CI) and III (CIII) form a CI–CIII supercomplex, but the degree of this assembly varies by cell type. In neurons, CI is predominantly integrated into supercomplexes, resulting in highly efficient mitochondrial respiration and minimal reactive oxygen species (ROS) generation. Conversely, in astrocytes, a larger fraction of CI remains unassembled, freely existing apart from CIII, leading to reduced respiratory efficiency and elevated mitochondrial ROS production. Despite this apparent inefficiency, astrocytes boast a highly adaptable metabolism capable of responding to diverse stressors. Their looser CI–CIII organization allows for flexible ROS signaling, which activates antioxidant programs via transcription factors like Nrf2. This modular architecture enables astrocytes not only to balance energy production but also to support neuronal health and influence complex organismal behaviors.

Distinct synaptic plasticity rules operate across dendritic compartments in vivo during learning