Memory formation and recall in recurrent spiking neural networks

Our brain has the capacity to analyze a visual scene in a split second, to learn how to play an instrument, and to remember events, faces and concepts. Neurons underlie all of these diverse functions. Neurons, cells within the brain that generate and transmit electrical activity, communicate with each other through chemical synapses. These synaptic connections dynamically change with experience, a process referred to as synaptic plasticity, which is thought to be at the core of the brain's ability to learn and process the world in sophisticated ways. Our understanding of the rules of synaptic plasticity remains quite limited. To enable efficient computations among neurons or to serve as a trace of memory, synapses must create stable connectivity patterns between neurons. However there remains an insufficient theoretical explanation as to how stable connectivity patterns can form in the presence of synaptic plasticity. Since the dynamics of recurrently connected neurons depend upon their connections, which themselves change in response to the network dynamics, synaptic plasticity and network dynamics have to be treated as a compound system. Due to the nonlinear nature of the system this can be analytically challenging. Utilizing network simulations that model the interplay between the network connectivity and synaptic plasticity can provide valuable insights. However, many existing network models that implement biologically relevant forms of plasticity become unstable. This suggests that current models do not accurately describe the biological networks, which have no difficulty functioning without succumbing to exploding network activity. The instability in these network simulations could originate from the fact that theoretical studies have, almost exclusively, focused on Hebbian plasticity at excitatory synapses. Hebbian plasticity causes connected neurons that are active together to increase the connection strength between them. Biological networks, however, display a large variety of different forms of synaptic plasticity and homeostatic mechanisms, beyond Hebbian plasticity. Furthermore, inhibitory cells can undergo synaptic plasticity as well. These diverse forms of plasticity are active at the same time, and our understanding of the computational role of most of these synaptic dynamics remains elusive. This raises the important question as to whether forms of plasticity that have not been previously considered could -in combination with Hebbian plasticity- lead to stable network dynamics. Here we illustrate that by combining multiple forms of plasticity with distinct roles, a recurrently connected spiking network model self-organizes to distinguish and extract multiple overlapping external stimuli. Moreover we show that the acquired network structures remain stable over hours while plasticity is active. This long-term stability allows the network to function as an associative memory and to correctly classify distorted or partially cued stimuli. During intervals in which no stimulus is shown the network dynamically remembers the last stimulus as selective delay activity. Taken together this work suggest that multiple forms of plasticity and homeostasis on different timescales have to work together to create stable connectivity patterns in neuronal networks which enable them to perform relevant computation.

Continuous attractor working memory and provenance of channel models

Alexander Kevin Seeholzer

The brain is a complex biological system composed of a multitude of microscopic processes, which together give rise to computational abilities observed in everyday behavior. Neuronal modeling, consisting of models of single neurons and neuronal networks at varying levels of biological detail, can synthesize the gaps currently hard to constrain in experiments and provide mechanistic explanations of how these computations might arise. In this thesis, I present two parallel lines of research on neuronal modeling, situated at varying levels of biological detail. First, I assess the provenance of voltage-gated ion channel models in an integrative meta-analysis that investigates a backlog of nearly 50 years of published research. To cope with the ever-increasing volume of research produced in the field of neuroscience, we need to develop methods for the systematic assessment and comparison of published work. As we demonstrate, neuronal models offer the intriguing possibility of performing automated quantitative analyses across studies, by standardized simulated experiments. We developed protocols for the quantitative comparison of voltage-gated ion channels, and applied them to a large body of published models, allowing us to assess the variety and temporal development of different models for the same ion channels over the time scale of years of research. Beyond a systematic classification of the existing body of research made available in an online platform, we show that our approach extends to large-scale comparisons of ion channel models to experimental data, thereby facilitating field-wide standardization of experimentally-constrained modeling. Second, I investigate neuronal models of working memory (WM). How can cortical networks bridge the short time scales of their microscopic components, which operate on the order of milliseconds, to the behaviorally relevant time scales of seconds observed in WM experiments? I consider here a candidate model: continuous attractor networks. These can implement WM for a continuum of possible spatial locations over several seconds and have been proposed for the organization of prefrontal cortical networks. I first present a novel method for the efficient prediction of the network-wide steady states from the underlying microscopic network properties. The method can be applied to predict and tune the "bump" shapes of continuous attractors implemented in networks of spiking neuron models connected by nonlinear synapses, which we demonstrate for saturating synapses involving NMDA receptors. In a second part, I investigate the computational role of short-term synaptic plasticity as a synaptic nonlinearity. Continuous attractor models are sensitive to the inevitable variability of biological neurons: variable neuronal firing and heterogeneous networks decrease the time that memories are accurately retained, eventually leading to a loss of memory functionality on behaviorally relevant time scales. In theory and simulations, I show that short-term plasticity can control the time scale of memory retention, with facilitation and depression playing antagonistic roles in controlling the drift and diffusion of locations in memory. Finally, we place quantitative constraints on the combination of synaptic and network parameters under which continuous attractors networks can implement reliable WM in cortical settings.

EPFL2017

How single neuron properties shape chaotic dynamics and signal transmission in random neural networks

Wulfram Gerstner, Samuel Pavio Muscinelli, Tilo Schwalger

While most models of randomly connected neural networks assume single-neuron models with simple dynamics, neurons in the brain exhibit complex intrinsic dynamics over multiple timescales. We analyze how the dynamical properties of single neurons and recurrent connections interact to shape the effective dynamics in large randomly connected networks. A novel dynamical mean-field theory for strongly connected networks of multi-dimensional rate neurons shows that the power spectrum of the network activity in the chaotic phase emerges from a nonlinear sharpening of the frequency response function of single neurons. For the case of two-dimensional rate neurons with strong adaptation, we find that the network exhibits a state of resonant chaos, characterized by robust, narrow-band stochastic oscillations. The coherence of stochastic oscillations is maximal at the onset of chaos and their correlation time scales with the adaptation timescale of single units. Surprisingly, the resonance frequency can be predicted from the properties of isolated neurons, even in the presence of heterogeneity in the adaptation parameters. In the presence of these internally-generated chaotic fluctuations, the transmission of weak, low-frequency signals is strongly enhanced by adaptation, whereas signal transmission is not influenced by adaptation in the non-chaotic regime. Our theoretical framework can be applied to other mechanisms at the level of single neurons, such as synaptic filtering, refractoriness or spike synchronization. These results advance our understanding of the interaction between the dynamics of single units and recurrent connectivity, which is a fundamental step toward the description of biologically realistic neural networks. Author summary Biological neural networks are formed by a large number of neurons whose interactions can be extremely complex. Such systems have been successfully studied using random network models, in which the interactions among neurons are assumed to be random. However, the dynamics of single units are usually described using over-simplified models, which might not capture several salient features of real neurons. Here, we show how accounting for richer single-neuron dynamics results in shaping the network dynamics and determines which signals are better transmitted. We focus on adaptation, an important mechanism present in biological neurons that consists in the decrease of their firing rate in response to a sustained stimulus. Our mean-field approach reveals that the presence of adaptation shifts the network into a previously unreported dynamical regime, that we term resonant chaos, in which chaotic activity has a strong oscillatory component. Moreover, we show that this regime is advantageous for the transmission of low-frequency signals. Our work bridges the microscopic dynamics (single neurons) to the macroscopic dynamics (network), and shows how the global signal-transmission properties of the network can be controlled by acting on the single-neuron dynamics. These results paves the way for further developments that include more complex neural mechanisms, and considerably advance our understanding of realistic neural networks.

2019

Hebbian plasticity requires compensatory processes on multiple timescales

Wulfram Gerstner, Friedemann Zenke

We review a body of theoretical and experimental research on Hebbian and homeostatic plasticity, starting from a puzzling observation: while homeostasis of synapses found in experiments is a slow compensatory process, most mathematical models of synaptic plasticity use rapid compensatory processes (RCPs). Even worse, with the slow homeostatic plasticity reported in experiments, simulations of existing plasticity models cannot maintain network stability unless further control mechanisms are implemented. To solve this paradox, we suggest that in addition to slow forms of homeostatic plasticity there are RCPs which stabilize synaptic plasticity on short timescales. These rapid processes may include heterosynaptic depression triggered by episodes of high postsynaptic firing rate. While slower forms of homeostatic plasticity are not sufficient to stabilize Hebbian plasticity, they are important for fine-tuning neural circuits. Taken together we suggest that learning and memory rely on an intricate interplay of diverse plasticity mechanisms on different timescales which jointly ensure stability and plasticity of neural circuits. This article is part of the themed issue 'Integrating Hebbian and homeostatic plasticity'.