Computational Neuroscience seminars

Theoretical neuroscience aims to understand the relationship between neuron dynamics and connectivity in recurrent circuits. This has been intensively studied at the local level, where dynamics is described by pairwise correlations. Recent advances in simultaneous recordings of many neurons have allowed researchers to address the question at the global level, such as for the dimensionality of population dynamics. Our work contributes to this effort by analyzing the impact of connectivity statistics, including certain motifs, on the bulk and outlier covariance eigenvalues. By considering linearized dynamics around a steady state, we obtained analytically the covariance spectrum which exhibits a signature long tail robust to model variants and matches zebrafish calcium imaging data. This provides a local circuit mechanism for shaping the geometry of population dynamics and a quantitative benchmark for interpreting data. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2024-05-22. Recording duration: 00:53:15.

Through recent advances in microscopy, we now have an unprecedented view of the brain and body of the fruit fly Drosophila melanogaster. We now know the connectivity at single neuron resolution across the whole brain. How do we translate these new measurements into a deeper understanding of how the brain processes sensory information and produces behavior? I will describe two computational efforts to model the brain and the body of the fruit fly. First, I will describe a new modeling method which makes highly accurate predictions of neural activity in the fly visual system as measured in the living brain, using only measurements of its connectivity from a dead brain [1], joint work with Jakob Macke. Second, I will describe a whole body physics simulation of the fruit fly which can accurately reproduce its locomotion behaviors, both flight and walking [2], joint work with Google DeepMind.

Understanding the causal connectivity within a network is crucial for unraveling its functional dynamics. However，the inferred causal connections are fundamentally influenced by the choice of causality measure employed, which may not always align with the actual structural connectivity of the network. The relationship between causal and structural connectivity, especially how different causality measures affect the inferred causal links, requires further exploration. In this talk, we examine nonlinear networks characterized by pulse signal outputs, such as spiking neural networks, using four prevalent causality measures: time-delayed correlation coefficient, time-delayed mutual information, Granger causality, and transfer entropy. We provide a theoretical analysis of the interconnections among these measures when applied to pulse signals. Utilizing both a simulated Hodgkin–Huxley network and an empirical mouse brain network as case studies, we validate the quantitative relationships between these causality measures. Our results show a strong correspondence between the causal connectivity derived from any of these measures and the actual structural connectivity, thereby establishing a direct linkage between them. We highlight that structural connectivity in networks with output pulse signals can be reconstructed on a pairwise basis, without needing global information from all network nodes, effectively avoiding the curse of dimensionality. Our approach offers a robust and practical methodology for reconstructing networks based on pulse outputs. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2024-05-08. Recording duration: 00:45:20.

Persistent, stimulus-dependent neuronal activity has been observed in numerous brain areas during tasks that require the temporary maintenance of information. Several competing hypotheses for the neuronal mechanisms underlying persistent activity have been proposed. We have employed data-driven models in conjunction with optogenetic disruptions of neural circuits within memory-guided motor tasks. Our findings revealed a mechanism governed by dynamic attractors, pivotal in sustaining neuronal activity. This mechanism, shaped by time-varying inputs reflecting temporal predictions, is instrumental in regulating the impact of sensory information on the premotor cortex, thereby preserving memory traces from distracting stimuli. We then asked how persistent activity driven by attractor dynamics emerges during motor learning. It has been proposed that activity-dependent synaptic plasticity underpins motor learning, as it can reconfigure network architectures to produce the appropriate neural dynamics for specific behaviors. To verify this hypothesis, we investigated how the mouse premotor cortex acquires specific neural dynamics that govern the planning of movement at different stages of motor learning. We developed network models that replicated the effects of acute manipulations of synaptic plasticity. The models, which display attractor dynamics, also explain flexible behavior after learning has ended. By leveraging the model's predictions, we can formulate testable hypotheses regarding the distinct mechanisms governing movement planning at various stages of the learning process. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2024-05-01. Recording duration: 00:39:52.

Neural computation is inextricably bound to decisions that must be made under time pressure and uncertainty. At the level of neural circuits, single neurons need to decide whether to spike. On longer timescales, the component circuitry needs to decide whether to reconfigure to store memories and adapt to novel situations. In this talk I will focus on two fun ideas in each of these contexts by showing how nonlinearities in neural components naturally form excitable switches that enable reliable decisions to be made in fluctuating environments. I will also issue propaganda that the kind of high level, cognitive faculties that we normally associate with decision making apply equally well and are understudied at the level of neural and synaptic populations. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2024-04-17. Recording duration: 00:41:08.

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 learn and represent 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 the hippocampus 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.

Learning in biological systems takes place in contexts and with dynamics not often accounted for by simple models. I will describe the learning dynamics of two model systems that incorporate either architectural or dynamic constraints from biological observations. In the first case, inspired by the observed mesoscopic structure of the mouse brain as revealed by the Allen Mouse Brain Connectivity Atlas, as well as multiple examples of parallel pathways in mammalian brains, I present a mathematical analysis of learning dynamics in networks that have parallel computational pathways driven by the same cost function. We use the approximation of deep linear networks with large hidden layer sizes to show that, as the depth of the parallel pathways increases, different features of the training set (defined by the singular values of the input-output correlation) will typically concentrate in one of the pathways. This result is derived analytically and demonstrated with numerical simulation with both linear and non-linear networks. Thus, rather than sharing stimulus and task features across multiple pathways, parallel network architectures learn to produce sharply diversified representations with specialized and specific pathways, a mechanism which may hold important consequences for codes in both biological and artificial systems. In the second case, I discuss learning dynamics in a generalization of Hebbian rules and show that these rules allow a neuron to learn tensor decompositions of higher-order input correlations. Unlike the case of the Oja rule and PCA, the resulting learned representation is not unique but selects amongst the tensor eigenvectors according to initial conditions. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2024-04-10. Recording duration: 00:30:39.

Inhibition has long been thought to stabilize the activity of cortical networks at low rates, and to shape significantly their response to sensory inputs. In this talk, I will describe three recent collaborative projects that shed light on these issues. (1) I will show how optogenetic excitation of inhibition neurons is consistent with cortex being inhibition stabilized even in the absence of sensory inputs, and how this data can constrain the coupling strengths of E-I cortical network models. (2) Recent analysis of the effects of optogenetic excitation of pyramidal cells in V1 of mice and monkeys shows that in some cases this optogenetic input reshuffles the firing rates of neurons of the network, leaving the distribution of rates unaffected. I will show how this surprising effect can be reproduced in sufficiently strongly coupled E-I networks. (3) Another puzzle has been to understand the respective roles of different inhibitory subtypes in network stabilization. Recent data reveal a novel, state dependent, paradoxical effect of weakening AMPAR mediated synaptic currents onto SST cells. Mathematical analysis of a network model with multiple inhibitory cell types shows that this effect tells us in which conditions SST cells are required for network stabilization.

In this talk, I will explain a theory of connectome-constrained neural networks in which a “student” networks is trained to reproduce the activity of a ground-truth “teacher”, representing a neural system for which a connectome is available. Unlike standard paradigms with unconstrained connectivity, here both networks have the same connectivity but they have different biophysical parameters, reflecting uncertainty in neuronal and synaptic properties. We find that the connectome is often insufficient to constrain the dynamics of networks that perform a specific task, illustrating the difficulty of inferring function from connectivity alone. However, recordings from a small subset of neurons can remove this degeneracy, producing dynamics in the student that agree with the teacher. Our theory can prioritize which neurons to record from to most efficiently unmeasured network activity. The analysis shows that the solution spaces of connectome-constrained and unconstrained models are qualitatively different, and provides a framework to determine when such models yield consistent dynamics. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2024-04-03. Recording duration: 00:42:28.

The connectivity structure of many biological systems, including neural circuits, is highly non-uniform. Recent technologies allow detailed mapping of these irregularities, but our understanding of their effect on the overall circuit dynamics is still lacking. By developing complex system analytical tools that perform reduction of the network, I determine the impact of connectivity features on network dynamics. I will demonstrate the use of these tools on neural assemblies (clusters), a ubiquitous non-uniform structure in our brains. I will show how neural assemblies of different sizes naturally generate multiple timescales of activity spanning several orders of magnitude. I will demonstrate how the analytical theory we develop for rate networks, supported by spiking network simulations, reveals the dependency between neural timescales and assembly sizes and how new recordings of spontaneous activity from a million neurons support this analysis. I will also show how our model can naturally explain the particular long-tailed timescale distribution observed in the awake primate cortex. In olfactory cortex, neural assemblies represent odor stimuli. Previously, I showed how the diffuse recurrent excitation among these assemblies allows the conversion of time-encoded inputs from the bulb to spacial neural assembly representations in olfactory cortex. Here, I will show how changes in the dynamical properties of these assemblies alter both their timing response and properties of the time-encoded inputs via feedback. This demonstrates the role of neural assemblies in time-sensitive modulation needed for cognitive tasks, such as attention. Our results offer a biologically plausible mechanism of assemblies in network connectivity for explaining multiple puzzling dynamical phenomena: The ability of neural circuits to transform external simultaneous temporal fluctuations into spatial representations and alter them; and the ability of neuronal circuits to generate simultaneous temporal fluctuations across a large range of timescales; Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2024-03-20. Recording duration: 00:41:28.

Predictive processing is a computational framework that aims to explain how the brain processes sensory information by making predictions about the environment and minimizing prediction errors. It can also be used to explain some of the key symptoms of psychotic disorders such as schizophrenia. In my talk, I will provide an overview of our progress in this endeavor.

In theoretical neuroscience, the brain is usually described as an information processing system that encodes and manipulates representations of knowledge to produce plans of action. This view leads to a decomposition of brain functions into putative processes such as object recognition, working memory, decision-making, action planning, etc., inspiring the search for the neural correlates of these processes. However, neurophysiological data do not support many of the predictions of these classic subdivisions. Instead, there is divergence and broad distribution of functions that should be unified, mixed representations combining functions that should be distinct, and a general incompatibility with the conceptual subdivisions posited by theories of information processing. In this talk, I will explore the possibility of resynthesizing a different set of functional subdivisions, guided by the growing body of data on the evolutionary process that produced the human brain. I will summarize, in chronological order, a proposed sequence of innovations that appeared in nervous systems along the lineage that leads from the earliest multicellular animals to humans. Along the way, functional subdivisions and elaborations will be introduced in parallel with the neural specializations that made them possible, gradually building up an alternative conceptual taxonomy of brain functions. These functions emphasize mechanisms for real-time interaction with the world, rather than for building explicit knowledge of the world, and the relevant representations emphasize pragmatic outcomes rather than decoding accuracy, mixing variables in the way seen in real neural data. I suggest that this alternative taxonomy may better delineate the real functional pieces into which the brain is organized, and can offer a more natural mapping between behavior and neural mechanisms. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2024-03-13. Recording duration: 00:52:50.

Cognitive maps confer animals with flexible intelligence by representing spatial, temporal, and abstract relationships that can be used to shape thought, planning, and behavior. Cognitive maps have been observed in the hippocampus, but their algorithmic form and the processes by which they are learned remain obscure. Here, we employed large-scale, longitudinal two-photon calcium imaging to record activity from thousands of neurons in the CA1 region of the hippocampus while mice learned to efficiently collect rewards from two subtly different versions of linear tracks in virtual reality. The results provide a detailed view of the formation of a cognitive map in the hippocampus. Throughout learning, both the animal behavior and hippocampal neural activity progressed through multiple intermediate stages, gradually revealing improved task representation that mirrored improved behavioral efficiency. The learning process led to progressive decorrelations in initially similar hippocampal neural activity within and across tracks, ultimately resulting in orthogonalized representations resembling a state machine capturing the inherent struture of the task. We show that a Hidden Markov Model (HMM) and a biologically plausible recurrent neural network trained using Hebbian learning can both capture core aspects of the learning dynamics and the orthogonalized representational structure in neural activity. In contrast, we show that gradient-based learning of sequence models such as Long Short-Term Memory networks (LSTMs) and Transformers do not naturally produce such orthogonalized representations. We further demonstrate that mice exhibited adaptive behavior in novel task settings, with neural activity reflecting flexible deployment of the state machine. These findings shed light on the mathematical form of cognitive maps, the learning rules that sculpt them, and the algorithms that promote adaptive behavior in animals. The work thus charts a course toward a deeper understanding of biological intelligence and offers insights toward developing more robust learning algorithms in artificial intelligence.

Lead author Mehdi Azabou will present on his work "POYO-1: A Unified, Scalable Framework for Neural Population Decoding" (https://poyo-brain.github.io/). Mehdi is an ML PhD student at Georgia Tech advised by Dr. Eva Dyer. Paper link: https://arxiv.org/abs/2310.16046 Trends in NeuroAI is a reading group hosted by the MedARC Neuroimaging & AI lab (https://medarc.ai/fmri | https://groups.google.com/g/medarc-fmri).

Performing learned behaviors requires animals to produce precisely timed motor sequences. The underlying neuronal circuits must convert incoming spike trains into precisely timed firing to indicate the onset of crucial sensory cues or to carry out well-coordinated muscle movements. Birdsong is a remarkable example of a complex, learned and precisely timed natural behavior which is controlled by a brainstem-thalamocortical feedback loop. Projection neurons within the zebra finch cortical nucleus HVC (used as a proper name), produce precisely timed, highly reliable and ultra-sparse neural sequences that are thought to underlie song dynamics. However, the origin of short timescale dynamics of the song is debated. One model posits that these dynamics reside in HVC and are mediated through a synaptic chain mechanism. Alternatively, the upstream motor thalamic nucleus Uveaformis (Uva), could drive HVC bursts as part of a brainstem-thalamocortical distributed network. Using focal temperature manipulation we found that the song dynamics reside chiefly in HVC. We then characterized the activity of thalamic nucleus Uva, which provides input to HVC. We developed a lightweight (~1 g) microdrive for juxtacellular recordings and with it performed the very first extracellular single unit recordings in Uva during song. Recordings revealed HVC-projecting Uva neurons contain timing information during the song, but compared to HVC neurons, fire densely in time and are much less reliable. Computational models of Uva-driven HVC neurons estimated that a high degree of synaptic convergence is needed from Uva to HVC to overcome the inconsistency of Uva firing patterns. However, axon terminals of single Uva neurons exhibit low convergence within HVC such that each HVC neuron receives input from 2-7 Uva neurons. These results suggest that thalamus maintains sequential cortical activity during song but does not provide unambiguous timing information. Our observations are consistent with a model in which the brainstem-thalamocortical feedback loop acts at the syllable timescale (~100 ms) and does not support a model in which the brainstem-thalamocortical feedback loop acts at fast timescale (~10 ms) to generate sequences within cortex. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2024-02-14. Recording duration: 00:39:45.

Remembering events in the past is crucial to intelligent behaviour. Flexible memory retrieval, beyond simple recall, requires a model of how events relate to one another. Two key brain systems are implicated in this process: the hippocampal episodic memory (EM) system and the prefrontal working memory (WM) system. While an understanding of the hippocampal system, from computation to algorithm and representation, is emerging, less is understood about how the prefrontal WM system can give rise to flexible computations beyond simple memory retrieval, and even less is understood about how the two systems relate to each other. Here we develop a mathematical theory relating the algorithms and representations of EM and WM by showing a duality between storing memories in synapses versus neural activity. In doing so, we develop a formal theory of the algorithm and representation of prefrontal WM as structured, and controllable, neural subspaces (termed activity slots). By building models using this formalism, we elucidate the differences, similarities, and trade-offs between the hippocampal and prefrontal algorithms. Lastly, we show that several prefrontal representations in tasks ranging from list learning to cue dependent recall are unified as controllable activity slots. Our results unify frontal and temporal representations of memory, and offer a new basis for understanding the prefrontal representation of WM

We build upon and expand the efficient coding and predictive information models of neurons, presenting a novel perspective that neurons not only predict but also actively influence their future inputs through their outputs. We introduce the concept of neurons as feedback controllers of their environments, a role traditionally considered computationally demanding, particularly when the dynamical system characterizing the environment is unknown. By harnessing a novel data-driven control framework, we illustrate the feasibility of biological neurons functioning as effective feedback controllers. This innovative approach enables us to coherently explain various experimental findings that previously seemed unrelated. Our research has profound implications, potentially revolutionizing the modeling of neuronal circuits and paving the way for the creation of alternative, biologically inspired artificial neural networks.

Animals and humans rapidly adapt their behavior to dynamic environmental changes, such as predator threats or fluctuating food resources, often without immediate rewards. Existing literature posits that animals rely on internal representations of the environment, termed “beliefs”, for their decision policy. However, previous work ties belief updates to external reward signals, which does not explain adaptation in scenarios where trial-and-error approaches are inefficient or potentially perilous. In this work, we propose that the brain utilize dynamic representations that continuously infer the state of the environment, allowing it to update behavior rapidly. I will present a Bayesian theory for state inference in a partially observed Markov Decision Process with multiple interacting latent variables. Optimal behavior requires knowledge of hidden interactions between latent states. I will show that recurrent neural networks trained through reinforcement solve the task by learning the hidden interaction between latent states, and their activity encodes the dynamics of the optimal Bayesian estimators. The behavior of rodents trained on an identical task aligns with our theoretical model and neural network simulations, suggesting that the brain utilizes dynamic internal state representation and inference. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2024-01-31. Recording duration: 00:51:21.