Computational Neuroscience seminars

Understanding the neural mechanisms of reward-guided learning is a long-standing goal of computational neuroscience. Recent methodological innovations enable us to collect ever larger neural and behavioral datasets. This presents opportunities to achieve greater understanding of learning in the brain at scale, as well as methodological challenges. In the first part of the talk, I will discuss our recent insights into the mechanisms by which zebra finch songbirds learn to sing. Dopamine has been long thought to guide reward-based trial-and-error learning by encoding reward prediction errors. However, it is unknown whether the learning of natural behaviours, such as developmental vocal learning, occurs through dopamine-based reinforcement. Longitudinal recordings of dopamine and bird songs reveal that dopamine activity is indeed consistent with encoding a reward prediction error during naturalistic learning. In the second part of the talk, I will talk about recent work we are doing at DeepMind to develop tools for automatically discovering interpretable models of behavior directly from animal choice data. Our method, dubbed CogFunSearch, uses LLMs within an evolutionary search process in order to "discover" novel models in the form of Python programs that excel at accurately predicting animal behavior during reward-guided learning. The discovered programs reveal novel patterns of learning and choice behavior that update our understanding of how the brain solves reinforcement learning problems.

n the neurosciences the need for some 'overarching' theory is sometimes expressed, but it is not always obvious what is meant by this. One can perhaps agree that in modern science observation and experimentation is normally complemented by 'theory', i.e. the development of theoretical concepts that help guiding and evaluating experiments and measurements. A deeper discussion of 'brain theory' will require the clarification of some further distictions, in particular: theory vs. model and brain research (and its theory) vs. neuroscience. Other questions are: Does a theory require mathematics? Or even differential equations? Today it is often taken for granted that the whole universe including everything in it, for example humans, animals, and plants, can be adequately treated by physics and therefore theoretical physics is the overarching theory. Even if this is the case, it has turned out that in some particular parts of physics (the historical example is thermodynamics) it may be useful to simplify the theory by introducing additional theoretical concepts that can in principle be 'reduced' to more complex descriptions on the 'microscopic' level of basic physical particals and forces. In this sense, brain theory may be regarded as part of theoretical neuroscience, which is inside biophysics and therefore inside physics, or theoretical physics. Still, in neuroscience and brain research, additional concepts are typically used to describe results and help guiding experimentation that are 'outside' physics, beginning with neurons and synapses, names of brain parts and areas, up to concepts like 'learning', 'motivation', 'attention'. Certainly, we do not yet have one theory that includes all these concepts. So 'brain theory' is still in a 'pre-newtonian' state. However, it may still be useful to understand in general the relations between a larger theory and its 'parts', or between microscopic and macroscopic theories, or between theories at different 'levels' of description. This is what I plan to do.

In 2023, the FlyWire Consortium released the neuronal wiring diagram of an adult fly brain. This contains as a corollary the first complete wiring diagram of a visual system, which has been used to identify all 200+ cell types that are intrinsic to the Drosophila optic lobe. About half of these cell types were previously unknown, and less than 20% have ever been recorded by a physiologist. I will argue that plausible functions for many cell types can be guessed by interpreting the wiring diagram. VVTNS Fifth Season Closing Lecture. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2025-06-25. Recording duration: 00:42:39.

We introduce a statistical physics framework for learning in neural architectures composed of single or interconnected asymmetric attractor networks. These systems can exhibit a manifold of global fixed points capable of implementing sophisticated input-output mappings, which we characterize analytically. Learning from extensive datasets is achieved through the stabilization of fixed points via a fully distributed and local learning process, implemented at the single-neuron level. This simple mechanism yields performance comparable to that of conventional feedforward deep neural networks trained using gradient-based methods. The effectiveness of the model stems from the dense and accessible manifolds of stable fixed points, which encode the internal representations of data. Unlike other approaches to deep learning without backpropagation, our method does not attempt to estimate gradients. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2025-06-18. Recording duration: 00:45:35.

In a first part of the talk, I will present Predictive Coding Light (PCL), a novel unsupervised learning architecture for spiking neural networks. In contrast to conventional predictive coding approaches, which only transmit prediction errors to higher processing stages, PCL learns inhibitory lateral and top-down connectivity to suppress the most predictable spikes and passes a compressed representation of the input to higher processing stages. We show that PCL reproduces a range of biological findings and exhibits a favorable tradeoff between energy consumption and downstream classification performance on challenging benchmarks. A second part of the talk will feature our lab’s efforts to explain how infants and toddlers might learn abstract object representations without supervision. I will present deep learning models that exploit the temporal and multimodal structure of their sensory inputs to learn representations of individual objects, object categories, or abstract super-categories such as „kitchen object“ in a fully unsupervised fashion. These models offer a parsimonious account of how abstract semantic knowledge may be rooted in children's embodied first-person experiences.

Understanding how brains learn requires bridging evidence across scales—from behaviour and neural circuits to cells, synapses, and molecules. In our work, we use computational modelling and data analysis to explore how the physical properties of neurons and neural circuits constrain learning. These include limits imposed by brain wiring, energy availability, molecular noise, and the 3D structure of dendritic spines. In this talk I will describe one such project testing if wiring motifs from fly brain connectomes can improve performance of reservoir computers, a type of recurrent neural network. The hope is that these insights into brain learning will lead to improved learning algorithms for artificial systems.

Measurements from hippocampal place cells in small enclosures have led to a classical view of highly stereotyped neural tuning functions with smooth, unimodal tuning fields that uniformly tile the environment. However, recent experiments conducted in large spaces across multiple species have revealed a much more irregular neural code than suggested by the classical view. Indeed, place cells in large environments typically fire in multiple locations, and the multiple firing fields of individual cells, as well as those of the entire population, vary considerably in size and shape. We recently showed that a simple mathematical model, wherein firing fields are generated by thresholding realizations of a random Gaussian process, accounts for the statistical properties of place fields in precise quantitative detail. This model captures the observed statistics of field sizes and positions and generates new quantitative predictions on field shapes and topologies. Moreover, these statistics are universal across species, but sensitive to the size and dimensionality of the environment. We quantitatively verified these predictions using multiple recent datasets from bats and rodents in one, two, and three dimensions, across both small and large environments. Collectively, these findings imply that common mechanism underlie the diverse statistical features observed in different experiments and suggest that synaptic projections to CA1 are predominantly random. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2025-05-28. Recording duration: 00:42:45.

When we attend a demanding task, our performance is poor at low arousal (when drowsy) or high arousal (when anxious), but we achieve optimal performance at intermediate arousal. This celebrated Yerkes-Dodson inverted-U law relating performance and arousal is colloquially referred to as being "in the zone." In this talk, I will elucidate the behavioral and neural mechanisms linking arousal and performance under the Yerkes-Dodson law in a mouse model. During decision-making tasks, mice express an array of discrete strategies, whereby the optimal strategy occurs at intermediate arousal, measured by pupil, consistent with the inverted-U law. Population recordings from the auditory cortex (A1) further revealed that sound encoding is optimal at intermediate arousal. To explain the computational principle underlying this inverted-U law, we modeled the A1 circuit as a spiking network with excitatory/inhibitory clusters, based on the observed functional clusters in A1. Arousal induced a transition from a multi-attractor (low arousal) to a single attractor phase (high arousal), and performance is optimized at the transition point. The model also predicts stimulus- and arousal-induced modulations of neural variability, which we confirmed in the data. Our theory suggests that a single unifying dynamical principle, phase transitions in metastable dynamics, underlies both the inverted-U law of optimal performance and state-dependent modulations of neural variability.

We have entered a golden age of artificial intelligence research, driven mainly by the advances in the artificial neural networks over the last several decades. Applications of these techniques—to machine vision, speech recognition, autonomous vehicles, natural language, and many other domains—are coming so quickly that many observers predict that the long-elusive goal of “Artificial General Intelligence” (AGI) is within our grasp. However, we still cannot build a machine capable of building a nest, stalking prey, or loading a dishwasher. I will describe how evolution may have shaped the algorithms that the brain is using to solve some of these challenging problems. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2025-05-21. Recording duration: 00:44:20.

All animal locomotion is rhythmic,whether it is achieved through undulatory movement of the whole body or the coordination of articulated limbs. Neurobiologists have long studied locomotor circuits that produce rhythmic activity with non-rhythmic input, also called central pattern generators (CPGs). However, the cellular and microcircuit implementation of a walking CPG has not been described for any limbed animal. New comprehensive connectomes of the fruit fly ventral nerve cord (VNC) provide an opportunity to study rhythmogenic walking circuits at a synaptic scale.We use a data-driven network modeling approach to identify and characterize a putative walking CPG in the Drosophila leg motor system.

My talk will consist of three subtopics. The brain remembers episodes not in isolation but with their contextual relationships, such as spatial or temporal proximity. This is an essential feature of the brain’s memory, but the underlying mechanism is yet to be explored. Cell assemblies, or engrams, may provide neural representations for such relationships. First, I will show a class of associative memory models that encode and retrieve multiple memory contents linked by an arbitrary graph structure through experience and demonstrate the crucial role of the balance between two inhibitory subnetwork types in the flexible retrieval of relational memories. Secondly, I propose a theoretical framework to generate a cognitive map, i.e., neural representations of relationships between memory items. This framework aims at the predictive function of the hippocampus and is based on successor representations proposed for reinforcement learning. Intriguingly, the model provides a unified account for grid cells in spatial navigation and concept cells in natural language processing. Finally, I will discuss another crucial role of the hippocampal memory system, memory replay, in a spiking neural network model. Unlike the conventional associative memory models that maintain attractor memory states, this model attempts to maximize the capacity of replayed activity patterns. Our model suggests the crucial role of inhibitory plasticity in optimizing spontaneous memory replay. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2025-05-14. Recording duration: 00:46:49.

Understanding the neural mechanisms of reward-guided learning is a long-standing goal of computational neuroscience. Recent methodological innovations enable us to collect ever larger neural and behavioral datasets. This presents opportunities to achieve greater understanding of learning in the brain at scale, as well as methodological challenges. In the first part of the talk, I will discuss our recent insights into the mechanisms by which zebra finch songbirds learn to sing. Dopamine has been long thought to guide reward-based trial-and-error learning by encoding reward prediction errors. However, it is unknown whether the learning of natural behaviours, such as developmental vocal learning, occurs through dopamine-based reinforcement. Longitudinal recordings of dopamine and bird songs reveal that dopamine activity is indeed consistent with encoding a reward prediction error during naturalistic learning. In the second part of the talk, I will talk about recent work we are doing at DeepMind to develop tools for automatically discovering interpretable models of behavior directly from animal choice data. Our method, dubbed CogFunSearch, uses LLMs within an evolutionary search process in order to "discover" novel models in the form of Python programs that excel at accurately predicting animal behavior during reward-guided learning. The discovered programs reveal novel patterns of learning and choice behavior that update our understanding of how the brain solves reinforcement learning problems.

The brain is one of the most energy intense organs. Some of this energyis used for neural information processing, however, fruitfly experiments have shown that also learning is metabolically costly. We will present estimates of this cost and introduce a general model of this cost, and compare it to costs in computers. Next, we turn to a supervised artificial network setting and explore a number of strategies that cansave energy need for plasticity. Either by modifying the objective function, by restricting plasticity, or by using less costly transient forms of plasticity. Finally, we will discuss adaptive strategies and possible relevance for biological learning. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2025-05-07. Recording duration: 00:34:58.

Neural dynamics represent the hard-to-interpret substrate of circuit computations. Advances in large-scale recordings have highlighted the sheer spatiotemporal complexity of circuit dynamics within and across circuits, portraying in detail the difficulty of interpreting such dynamics and relating it to computation. Indeed, even in extremely simplified experimental conditions, one observes high-dimensional temporal dynamics in the relevant circuits. This complexity can be potentially addressed by the notion that not all changes in population activity have equal meaning, i.e., a small change in the evolution of activity along a particular dimension may have a bigger effect on a given computation than a large change in another. We term such conditions dimension-specific computation. Considering motor preparatory activity in a delayed response task we utilized neural recordings performed simultaneously with optogenetic perturbations to probe circuit dynamics. First, we revealed a remarkable robustness in the detailed evolution of certain dimensions of the population activity, beyond what was thought to be the case experimentally and theoretically. Second, the robust dimension in activity space carries nearly all of the decodable behavioral information whereas other non-robust dimensions contained nearly no decodable information, as if the circuit was setup to make informative dimensions stiff, i.e., resistive to perturbations, leaving uninformative dimensions sloppy, i.e., sensitive to perturbations. Third, we show that this robustness can be achieved by a modular organization of circuitry, whereby modules whose dynamics normally evolve independently can correct each other’s dynamics when an individual module is perturbed, a common design feature in robust systems engineering. Finally, we will recent work extending this framework to understanding the neural dynamics underlying preparation of speech.

For decades dynamical systems theory played a pivotal role in theoretical and computational neuroscience, as it links biophysical and biochemical processes to neural computation. In fact, dynamical systems are computationally universal. Rather than hand-crafting computational theories of neural function based on dynamical systems, recent developments in scientific machine learning (ML) and AI suggest that we may be able to infer such dynamical-computational models directly from neurophysiological and behavioral observations. This is called dynamical systems reconstruction (DSR), the learning of generative surrogate models of the underlying dynamics, including its long-term temporal and geometrical properties, from time series data. In my talk I will cover recent ML/AI architectures, training algorithms, and validation procedures for DSR. I will discuss specifically how recent AI architectures for DSR can integrate neuroscience data from multiple modalities (like multiple single-unit recordings and behavioral choices), across diverse time scales, and across many different animals and task designs, into a joint DSR model. This provides first steps toward dynamical systems based AI foundation models for neuroscience. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2025-04-23. Recording duration: 00:53:24.

Over the past decade, neuroscience, cognitive science and computer science (“AI”) converged to create specific, image-computable, deep neural network models intended to appropriately abstract, emulate and explain the mechanisms of primate ventral visual processing, up to its deepest neural level, the inferior temporal cortex (IT). Because these leading neuroscientific emulation models — aka “digital twins” — are fully observable and machine-executable, they offer predictive and potential application power that our field’s prior conceptual models did not. Our team’s ongoing work is aimed at asking if current digital twin models might support non-invasive, beneficial brain modulation. In this talk, I will describe a key result: we demonstrate that we can use a digital twin to design spatial patterns of light energy that, when “added” to the organism’s retinal input in the context of ongoing natural visual processing, results in precise modulation (i.e. rate bias) of the pattern of a population of IT neurons (where any intended modulation pattern is chosen ahead of time by the scientist). Because the IT visual neural populations are known to directly connect to and modulate downstream neural circuits (e.g. amygdala) that may underlie psychological affective states (e.g. mood and anxiety), this novel basic science may unlock a new, non-invasive application avenue of potential future human clinical benefit. This progress and new impact possibilities resulted from convergent brain science and AI engineering efforts in the domain of visual object intelligence. I will motivate this as just one example of what I believe will unlock in other domains of human intelligence as brain scientists and AI engineers collaborate to develop machine-executable models of the underlying mechanisms of those still-mysterious domains. CARL VAN VREESWIJK MEMORIAL LECTURE 2025. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2025-04-09. Recording duration: 00:55:49.

The use of electronic circuits to model neural systems goes back to C. Mead and is present in models, from leaky-integrate-and-fire to Hodking-Huxley. Simulating neural network with analog hardware is attractive: it allows to implement neurocomputations in real time without discretization approximations, it has perfect simulation-time scaling with system size, and it provides ready-to-deploy neuromorphic circuit for applications. There are implementations in CMOS technology, however, they are complex, require sophisticated fabrication facilities and, most important, suffer from significant device mismatch. In a radically different approach, based on the concept of memristors, we introduce a neuro-synaptic circuit of unprecedented simplicity, with readily available cheap off-the-shelf electronic components, that can quantitatively reproduce textbook theoretical neuron and synaptic current models. Our neuron circuits can avoid the mismatch problem and are easily tuneable at bio-compatible time-scales. We first introduce a voltage-gated conductance bursting neuron model that produces spike traces that bare striking similarity to experimental recordings. We then introduce synaptic current circuits and show the modularity of our method implementing neurocomputing primitives of basic network motifs, including CPGs. With this "theoretical hardware" approach we show: (i) that neuron adaptation and self-excitation can be viewed as a self-consistent dynamical problem; (ii) that a dynamical memory can be minimally implemented with a single recursive spiking neuron; (iii) that an adaptive membrane current reveals a connection between bursting and the driven harmonic oscillator, perhaps pointing to a neural correlate of the pendular limb motion. Finally we discuss the limitation of the approach to networks of mid-size and its potential application for brain-machine-interfaces, robotics and AI. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2025-03-19. Recording duration: 00:43:46.

A major challenge in sensory systems is to understand how neurons extract information from the natural environment. Models derived from their responses to artificial stimuli often have a hard time to generalize and predict responses to natural scenes. However, models directly learned on the responses to natural scenes can be hard to interpret. To address this issue, we have recently developed an approach where we add small perturbations to natural scenes and measure how these perturbations change neuronal responses, to better understand the features extracted by sensory neurons. I will show several applications of this approach in the retina, and how it allowed us to uncover non-linear computations performed by ganglion cells, the retinal output. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2025-03-12. Recording duration: 00:47:06.