Purely STDP-based assembly dynamics: Stability, learning, overlaps, drift and aging.

Memories may be encoded in the brain via strongly interconnected groups of neurons, called assemblies. The concept of Hebbian plasticity suggests that these assemblies are generated through synaptic plasticity, strengthening the recurrent connections within select groups of neurons that receive correlated stimulation. To remain stable in absence of such stimulation, the assemblies need to be self-reinforcing under the plasticity rule. Previous models of such assembly maintenance require additional mechanisms of fast homeostatic plasticity often with biologically implausible timescales. Here we provide a model of neuronal assembly generation and maintenance purely based on spike-timing-dependent plasticity (STDP) between excitatory neurons. It uses irregularly and stochastically spiking neurons and STDP that depresses connections of uncorrelated neurons. We find that assemblies do not grow beyond a certain size, because temporally imprecisely correlated spikes dominate the plasticity in large assemblies. Assemblies in the model can be learned or spontaneously emerge. The model allows for prominent, stable overlap structures between static assemblies. Further, assemblies can drift, particularly according to a novel, transient overlap-based mechanism. Finally the model indicates that assemblies grow in the aging brain, where connectivity decreases.

High-frequency oscillations and sequence generation in two-population models of hippocampal region CA1.

Hippocampal sharp wave/ripple oscillations are a prominent pattern of collective activity, which consists of a strong overall increase of activity with superimposed (140 - 200 Hz) ripple oscillations. Despite its prominence and its experimentally demonstrated importance for memory consolidation, the mechanisms underlying its generation are to date not understood. Several models assume that recurrent networks of inhibitory cells alone can explain the generation and main characteristics of the ripple oscillations. Recent experiments, however, indicate that in addition to inhibitory basket cells, the pattern requires in vivo the activity of the local population of excitatory pyramidal cells. Here, we study a model for networks in the hippocampal region CA1 incorporating such a local excitatory population of pyramidal neurons. We start by investigating its ability to generate ripple oscillations using extensive simulations. Using biologically plausible parameters, we find that short pulses of external excitation triggering excitatory cell spiking are required for sharp/wave ripple generation with oscillation patterns similar to in vivo observations. Our model has plausible values for single neuron, synapse and connectivity parameters, random connectivity and no strong feedforward drive to the inhibitory population. Specifically, whereas temporally broad excitation can lead to high-frequency oscillations in the ripple range, sparse pyramidal cell activity is only obtained with pulse-like external CA3 excitation. Further simulations indicate that such short pulses could originate from dendritic spikes in the apical or basal dendrites of CA1 pyramidal cells, which are triggered by coincident spike arrivals from hippocampal region CA3. Finally we show that replay of sequences by pyramidal neurons and ripple oscillations can arise intrinsically in CA1 due to structured connectivity that gives rise to alternating excitatory pulse and inhibitory gap coding; the latter denotes phases of silence in specific basket cell groups, which induce selective disinhibition of groups of pyramidal neurons. This general mechanism for sequence generation leads to sparse pyramidal cell and dense basket cell spiking, does not rely on synfire chain-like feedforward excitation and may be relevant for other brain regions as well.

Drifting assemblies for persistent memory: Neuron transitions and unsupervised compensation.

Change is ubiquitous in living beings. In particular, the connectome and neural representations can change. Nevertheless, behaviors and memories often persist over long times. In a standard model, associative memories are represented by assemblies of strongly interconnected neurons. For faithful storage these assemblies are assumed to consist of the same neurons over time. Here we propose a contrasting memory model with complete temporal remodeling of assemblies, based on experimentally observed changes of synapses and neural representations. The assemblies drift freely as noisy autonomous network activity and spontaneous synaptic turnover induce neuron exchange. The gradual exchange allows activity-dependent and homeostatic plasticity to conserve the representational structure and keep inputs, outputs, and assemblies consistent. This leads to persistent memory. Our findings explain recent experimental results on temporal evolution of fear memory representations and suggest that memory systems need to be understood in their completeness as individual parts may constantly change.

Dynamical Learning of Dynamics.

The ability of humans and animals to quickly adapt to novel tasks is difficult to reconcile with the standard paradigm of learning by slow synaptic weight modification. Here, we show that fixed-weight neural networks can learn to generate required dynamics by imitation. After appropriate weight pretraining, the networks quickly and dynamically adapt to learn new tasks and thereafter continue to achieve them without further teacher feedback. We explain this ability and illustrate it with a variety of target dynamics, ranging from oscillatory trajectories to driven and chaotic dynamical systems.

From single neurons to behavior in the jellyfish Aurelia aurita.

Jellyfish nerve nets provide insight into the origins of nervous systems, as both their taxonomic position and their evolutionary age imply that jellyfish resemble some of the earliest neuron-bearing, actively-swimming animals. Here, we develop the first neuronal network model for the nerve nets of jellyfish. Specifically, we focus on the moon jelly Aurelia aurita and the control of its energy-efficient swimming motion. The proposed single neuron model disentangles the contributions of different currents to a spike. The network model identifies factors ensuring non-pathological activity and suggests an optimization for the transmission of signals. After modeling the jellyfish's muscle system and its bell in a hydrodynamic environment, we explore the swimming elicited by neural activity. We find that different delays between nerve net activations lead to well-controlled, differently directed movements. Our model bridges the scales from single neurons to behavior, allowing for a comprehensive understanding of jellyfish neural control of locomotion.

Dynamics and computation in mixed networks containing neurons that accelerate towards spiking.

Networks in the brain consist of different types of neurons. Here we investigate the influence of neuron diversity on the dynamics, phase space structure, and computational capabilities of spiking neural networks. We find that already a single neuron of a different type can qualitatively change the network dynamics and that mixed networks may combine the computational capabilities of ones with a single-neuron type. We study inhibitory networks of concave leaky (LIF) and convex "antileaky" (XIF) integrate-and-fire neurons that generalize irregularly spiking nonchaotic LIF neuron networks. Endowed with simple conductance-based synapses for XIF neurons, our networks can generate a balanced state of irregular asynchronous spiking as well. We determine the voltage probability distributions and self-consistent firing rates assuming Poisson input with finite-size spike impacts. Further, we compute the full spectrum of Lyapunov exponents (LEs) and the covariant Lyapunov vectors (CLVs) specifying the corresponding perturbation directions. We find that there is approximately one positive LE for each XIF neuron. This indicates in particular that a single XIF neuron renders the network dynamics chaotic. A simple mean-field approach, which can be justified by properties of the CLVs, explains the finding. As an application, we propose a spike-based computing scheme where our networks serve as computational reservoirs and their different stability properties yield different computational capabilities.

Altered Dynamics of Canonical Feedback Inhibition Predicts Increased Burst Transmission in Chronic Epilepsy.

Inhibitory interneurons, organized into canonical feedforward and feedback motifs, play a key role in controlling normal and pathological neuronal activity. We demonstrate prominent quantitative changes in the dynamics of feedback inhibition in a rat model of chronic epilepsy (male Wistar rats). Systematic interneuron recordings revealed a large decrease in intrinsic excitability of basket cells and oriens-lacunosum moleculare interneurons in epileptic animals. Additionally, the temporal dynamics of interneuron recruitment by recurrent feedback excitation were strongly altered, resulting in a profound loss of initial feedback inhibition during synchronous CA1 pyramidal activity. Biophysically constrained models of the complete feedback circuit motifs of normal and epileptic animals revealed that, as a consequence of altered feedback inhibition, burst activity arising in CA3 is more strongly converted to a CA1 output. This suggests that altered dynamics of feedback inhibition promote the transmission of epileptiform bursts to hippocampal projection areas.SIGNIFICANCE STATEMENT We quantitatively characterized changes of the CA1 feedback inhibitory circuit in a model of chronic temporal lobe epilepsy. This study shows, for the first time, that dynamic recruitment of inhibition in feedback circuits is altered and establishes the cellular mechanisms for this change. Computational modeling revealed that the observed changes are likely to systematically alter CA1 input-output properties leading to (1) increased seizure propagation through CA1 and (2) altered computation of synchronous CA3 input.

Analyzing the competition of gamma rhythms with delayed pulse-coupled oscillators in phase representation.

Networks of neurons can generate oscillatory activity as result of various types of coupling that lead to synchronization. A prominent type of oscillatory activity is gamma (30-80 Hz) rhythms, which may play an important role in neuronal information processing. Two mechanisms have mainly been proposed for their generation: (1) interneuron network gamma (ING) and (2) pyramidal-interneuron network gamma (PING). In vitro and in vivo experiments have shown that both mechanisms can exist in the same cortical circuits. This raises the questions: How do ING and PING interact when both can in principle occur? Are the network dynamics a superposition, or do ING and PING interact in a nonlinear way and if so, how? In this article, we first generalize the phase representation for nonlinear one-dimensional pulse coupled oscillators as introduced by Mirollo and Strogatz to type II oscillators whose phase response curve (PRC) has zero crossings. We then give a full theoretical analysis for the regular gamma-like oscillations of simple networks consisting of two neural oscillators, an "E neuron" mimicking a synchronized group of pyramidal cells, and an "I neuron" representing such a group of interneurons. Motivated by experimental findings, we choose the E neuron to have a type I PRC [leaky integrate-and-fire (LIF) neuron], while the I neuron has either a type I or type II PRC (LIF or "sine" neuron). The phase representation allows us to define in a simple manner scenarios of interaction between the two neurons, which are independent of the types and the details of the neuron models. The presence of delay in the couplings leads to an increased number of scenarios relevant for gamma-like oscillatory patterns. We analytically derive the set of such scenarios and describe their occurrence in terms of parameter values such as synaptic connectivity and drive to the E and I neurons. The networks can be tuned to oscillate in an ING or PING mode. We focus particularly on the transition region where both rhythms compete to govern the network dynamics and compare with oscillations in reduced networks, which can only generate either ING or PING. Our analytically derived oscillation frequency diagrams indicate that except for small coexistence regions, the networks generate ING if the oscillation frequency of the reduced ING network exceeds that of the reduced PING network, and vice versa. For networks with the LIF I neuron, the network oscillation frequency slightly exceeds the frequencies of corresponding reduced networks, while it lies between them for networks with the sine I neuron. In networks oscillating in ING (PING) mode, the oscillation frequency responds faster to changes in the drive to the I (E) neuron than to changes in the drive to the E (I) neuron. This finding suggests a method to analyze which mechanism governs an observed network oscillation. Notably, also when the network operates in ING mode, the E neuron can spike before the I neuron such that relative spike times of the pyramidal cells and the interneurons alone are not conclusive for distinguishing ING and PING.

Growing Critical: Self-Organized Criticality in a Developing Neural System.

Experiments in various neural systems found avalanches: bursts of activity with characteristics typical for critical dynamics. A possible explanation for their occurrence is an underlying network that self-organizes into a critical state. We propose a simple spiking model for developing neural networks, showing how these may "grow into" criticality. Avalanches generated by our model correspond to clusters of widely applied Hawkes processes. We analytically derive the cluster size and duration distributions and find that they agree with those of experimentally observed neuronal avalanches.

Learning Universal Computations with Spikes.

Providing the neurobiological basis of information processing in higher animals, spiking neural networks must be able to learn a variety of complicated computations, including the generation of appropriate, possibly delayed reactions to inputs and the self-sustained generation of complex activity patterns, e.g. for locomotion. Many such computations require previous building of intrinsic world models. Here we show how spiking neural networks may solve these different tasks. Firstly, we derive constraints under which classes of spiking neural networks lend themselves to substrates of powerful general purpose computing. The networks contain dendritic or synaptic nonlinearities and have a constrained connectivity. We then combine such networks with learning rules for outputs or recurrent connections. We show that this allows to learn even difficult benchmark tasks such as the self-sustained generation of desired low-dimensional chaotic dynamics or memory-dependent computations. Furthermore, we show how spiking networks can build models of external world systems and use the acquired knowledge to control them.

Building functional networks of spiking model neurons.

Most of the networks used by computer scientists and many of those studied by modelers in neuroscience represent unit activities as continuous variables. Neurons, however, communicate primarily through discontinuous spiking. We review methods for transferring our ability to construct interesting networks that perform relevant tasks from the artificial continuous domain to more realistic spiking network models. These methods raise a number of issues that warrant further theoretical and experimental study.

Cooperation and competition of gamma oscillation mechanisms.

Oscillations of neuronal activity in different frequency ranges are thought to reflect important aspects of cortical network dynamics. Here we investigate how various mechanisms that contribute to oscillations in neuronal networks may interact. We focus on networks with inhibitory, excitatory, and electrical synapses, where the subnetwork of inhibitory interneurons alone can generate interneuron gamma (ING) oscillations and the interactions between interneurons and pyramidal cells allow for pyramidal-interneuron gamma (PING) oscillations. What type of oscillation will such a network generate? We find that ING and PING oscillations compete: The mechanism generating the higher oscillation frequency "wins"; it determines the frequency of the network oscillation and suppresses the other mechanism. For type I interneurons, the network oscillation frequency is equal to or slightly above the higher of the ING and PING frequencies in corresponding reduced networks that can generate only either of them; if the interneurons belong to the type II class, it is in between. In contrast to ING and PING, oscillations mediated by gap junctions and oscillations mediated by inhibitory synapses may cooperate or compete, depending on the type (I or II) of interneurons and the strengths of the electrical and chemical synapses. We support our computer simulations by a theoretical model that allows a full theoretical analysis of the main results. Our study suggests experimental approaches to deciding to what extent oscillatory activity in networks of interacting excitatory and inhibitory neurons is dominated by ING or PING oscillations and of which class the participating interneurons are.

A Unified Dynamic Model for Learning, Replay, and Sharp-Wave/Ripples.

Hippocampal activity is fundamental for episodic memory formation and consolidation. During phases of rest and sleep, it exhibits sharp-wave/ripple (SPW/R) complexes, which are short episodes of increased activity with superimposed high-frequency oscillations. Simultaneously, spike sequences reflecting previous behavior, such as traversed trajectories in space, are replayed. Whereas these phenomena are thought to be crucial for the formation and consolidation of episodic memory, their neurophysiological mechanisms are not well understood. Here we present a unified model showing how experience may be stored and thereafter replayed in association with SPW/Rs. We propose that replay and SPW/Rs are tightly interconnected as they mutually generate and support each other. The underlying mechanism is based on the nonlinear dendritic computation attributable to dendritic sodium spikes that have been prominently found in the hippocampal regions CA1 and CA3, where SPW/Rs and replay are also generated. Besides assigning SPW/Rs a crucial role for replay and thus memory processing, the proposed mechanism also explains their characteristic features, such as the oscillation frequency and the overall wave form. The results shed a new light on the dynamical aspects of hippocampal circuit learning. SIGNIFICANCE STATEMENT: During phases of rest and sleep, the hippocampus, the "memory center" of the brain, generates intermittent patterns of strongly increased overall activity with high-frequency oscillations, the so-called sharp-wave/ripples. We investigate their role in learning and memory processing. They occur together with replay of activity sequences reflecting previous behavior. Developing a unifying computational model, we propose that both phenomena are tightly linked, by mutually generating and supporting each other. The underlying mechanism depends on nonlinear amplification of synchronous inputs that has been prominently found in the hippocampus. Besides assigning sharp-wave/ripples a crucial role for replay generation and thus memory processing, the proposed mechanism also explains their characteristic features, such as the oscillation frequency and the overall wave form.

Oscillation-induced signal transmission and gating in neural circuits.

Reliable signal transmission constitutes a key requirement for neural circuit function. The propagation of synchronous pulse packets through recurrent circuits is hypothesized to be one robust form of signal transmission and has been extensively studied in computational and theoretical works. Yet, although external or internally generated oscillations are ubiquitous across neural systems, their influence on such signal propagation is unclear. Here we systematically investigate the impact of oscillations on propagating synchrony. We find that for standard, additive couplings and a net excitatory effect of oscillations, robust propagation of synchrony is enabled in less prominent feed-forward structures than in systems without oscillations. In the presence of non-additive coupling (as mediated by fast dendritic spikes), even balanced oscillatory inputs may enable robust propagation. Here, emerging resonances create complex locking patterns between oscillations and spike synchrony. Interestingly, these resonances make the circuits capable of selecting specific pathways for signal transmission. Oscillations may thus promote reliable transmission and, in co-action with dendritic nonlinearities, provide a mechanism for information processing by selectively gating and routing of signals. Our results are of particular interest for the interpretation of sharp wave/ripple complexes in the hippocampus, where previously learned spike patterns are replayed in conjunction with global high-frequency oscillations. We suggest that the oscillations may serve to stabilize the replay.

Learning precisely timed spikes.

To signal the onset of salient sensory features or execute well-timed motor sequences, neuronal circuits must transform streams of incoming spike trains into precisely timed firing. To address the efficiency and fidelity with which neurons can perform such computations, we developed a theory to characterize the capacity of feedforward networks to generate desired spike sequences. We find the maximum number of desired output spikes a neuron can implement to be 0.1-0.3 per synapse. We further present a biologically plausible learning rule that allows feedforward and recurrent networks to learn multiple mappings between inputs and desired spike sequences. We apply this framework to reconstruct synaptic weights from spiking activity and study the precision with which the temporal structure of ongoing behavior can be inferred from the spiking of premotor neurons. This work provides a powerful approach for characterizing the computational and learning capacities of single neurons and neuronal circuits.

Hub-activated signal transmission in complex networks.

A wide range of networked systems exhibit highly connected nodes (hubs) as prominent structural elements. The functional roles of hubs in the collective nonlinear dynamics of many such networks, however, are not well understood. Here, we propose that hubs in neural circuits may activate local signal transmission along sequences of specific subnetworks. Intriguingly, in contrast to previous suggestions of the functional roles of hubs, here, not the hubs themselves, but nonhub subnetworks transfer the signals. The core mechanism relies on hubs and nonhubs providing activating feedback to each other. It may, thus, induce the propagation of specific pulse and rate signals in neuronal and other communication networks.

Propagating synchrony in feed-forward networks.

Coordinated patterns of precisely timed action potentials (spikes) emerge in a variety of neural circuits but their dynamical origin is still not well understood. One hypothesis states that synchronous activity propagating through feed-forward chains of groups of neurons (synfire chains) may dynamically generate such spike patterns. Additionally, synfire chains offer the possibility to enable reliable signal transmission. So far, mostly densely connected chains, often with all-to-all connectivity between groups, have been theoretically and computationally studied. Yet, such prominent feed-forward structures have not been observed experimentally. Here we analytically and numerically investigate under which conditions diluted feed-forward chains may exhibit synchrony propagation. In addition to conventional linear input summation, we study the impact of non-linear, non-additive summation accounting for the effect of fast dendritic spikes. The non-linearities promote synchronous inputs to generate precisely timed spikes. We identify how non-additive coupling relaxes the conditions on connectivity such that it enables synchrony propagation at connectivities substantially lower than required for linearly coupled chains. Although the analytical treatment is based on a simple leaky integrate-and-fire neuron model, we show how to generalize our methods to biologically more detailed neuron models and verify our results by numerical simulations with, e.g., Hodgkin Huxley type neurons.

Non-additive coupling enables propagation of synchronous spiking activity in purely random networks.

Despite the current debate about the computational role of experimentally observed precise spike patterns it is still theoretically unclear under which conditions and how they may emerge in neural circuits. Here, we study spiking neural networks with non-additive dendritic interactions that were recently uncovered in single-neuron experiments. We show that supra-additive dendritic interactions enable the persistent propagation of synchronous activity already in purely random networks without superimposed structures and explain the mechanism underlying it. This study adds a novel perspective on the dynamics of networks with nonlinear interactions in general and presents a new viable mechanism for the occurrence of patterns of precisely timed spikes in recurrent networks.

Quantitative prediction of intermittent high-frequency oscillations in neural networks with supralinear dendritic interactions.

The explanation of higher neural processes requires an understanding of the dynamics of complex, spiking neural networks. So far, modeling studies have focused on networks with linear or sublinear dendritic input summation. However, recent single-neuron experiments have demonstrated strongly supralinear dendritic enhancement of synchronous inputs. What are the implications of this amplification for networks of neurons? Here, I show numerically and analytically that such networks can generate intermittent, strong increases of activity with high-frequency oscillations; the models developed predict the shape of these events and the oscillation frequency. As an example, for the hippocampal region CA1, events with 200-Hz oscillations are predicted. I argue that these dynamics provide a plausible explanation for experimentally observed sharp-wave/ripple events. High-frequency oscillations can involve the replay of spike patterns. The models suggest that these patterns may reflect underlying network structures.

How Chaotic is the Balanced State?

Large sparse circuits of spiking neurons exhibit a balanced state of highly irregular activity under a wide range of conditions. It occurs likewise in sparsely connected random networks that receive excitatory external inputs and recurrent inhibition as well as in networks with mixed recurrent inhibition and excitation. Here we analytically investigate this irregular dynamics in finite networks keeping track of all individual spike times and the identities of individual neurons. For delayed, purely inhibitory interactions we show that the irregular dynamics is not chaotic but stable. Moreover, we demonstrate that after long transients the dynamics converges towards periodic orbits and that every generic periodic orbit of these dynamical systems is stable. We investigate the collective irregular dynamics upon increasing the time scale of synaptic responses and upon iteratively replacing inhibitory by excitatory interactions. Whereas for small and moderate time scales as well as for few excitatory interactions, the dynamics stays stable, there is a smooth transition to chaos if the synaptic response becomes sufficiently slow (even in purely inhibitory networks) or the number of excitatory interactions becomes too large. These results indicate that chaotic and stable dynamics are equally capable of generating the irregular neuronal activity. More generally, chaos apparently is not essential for generating the high irregularity of balanced activity, and we suggest that a mechanism different from chaos and stochasticity significantly contributes to irregular activity in cortical circuits.