A robust balancing mechanism for spiking neural networks.

Dynamical balance of excitation and inhibition is usually invoked to explain the irregular low firing activity observed in the cortex. We propose a robust nonlinear balancing mechanism for a random network of spiking neurons, which works also in the absence of strong external currents. Biologically, the mechanism exploits the plasticity of excitatory-excitatory synapses induced by short-term depression. Mathematically, the nonlinear response of the synaptic activity is the key ingredient responsible for the emergence of a stable balanced regime. Our claim is supported by a simple self-consistent analysis accompanied by extensive simulations performed for increasing network sizes. The observed regime is essentially fluctuation driven and characterized by highly irregular spiking dynamics of all neurons.

Gamma oscillatory complexity conveys behavioral information in hippocampal networks.

The hippocampus and entorhinal cortex exhibit rich oscillatory patterns critical for cognitive functions. In the hippocampal region CA1, specific gamma-frequency oscillations, timed at different phases of the ongoing theta rhythm, are hypothesized to facilitate the integration of information from varied sources and contribute to distinct cognitive processes. Here, we show that gamma elements -a multidimensional characterization of transient gamma oscillatory episodes- occur at any frequency or phase relative to the ongoing theta rhythm across all CA1 layers in male mice. Despite their low power and stochastic-like nature, individual gamma elements still carry behavior-related information and computational modeling suggests that they reflect neuronal firing. Our findings challenge the idea of rigid gamma sub-bands, showing that behavior shapes ensembles of irregular gamma elements that evolve with learning and depend on hippocampal layers. Widespread gamma diversity, beyond randomness, may thus reflect complexity, likely functional but invisible to classic average-based analyses.

Inhibitory neurons control the consolidation of neural assemblies via adaptation to selective stimuli.

Brain circuits display modular architecture at different scales of organization. Such neural assemblies are typically associated to functional specialization but the mechanisms leading to their emergence and consolidation still remain elusive. In this paper we investigate the role of inhibition in structuring new neural assemblies driven by the entrainment to various inputs. In particular, we focus on the role of partially synchronized dynamics for the creation and maintenance of structural modules in neural circuits by considering a network of excitatory and inhibitory [Formula: see text]-neurons with plastic Hebbian synapses. The learning process consists of an entrainment to temporally alternating stimuli that are applied to separate regions of the network. This entrainment leads to the emergence of modular structures. Contrary to common practice in artificial neural networks-where the acquired weights are typically frozen after the learning session-we allow for synaptic adaptation even after the learning phase. We find that the presence of inhibitory neurons in the network is crucial for the emergence and the post-learning consolidation of the modular structures. Indeed networks made of purely excitatory neurons or of neurons not respecting Dale's principle are unable to form or to maintain the modular architecture induced by the stimuli. We also demonstrate that the number of inhibitory neurons in the network is directly related to the maximal number of neural assemblies that can be consolidated, supporting the idea that inhibition has a direct impact on the memory capacity of the neural network.

Population spiking and bursting in next-generation neural masses with spike-frequency adaptation.

Spike-frequency adaptation (SFA) is a fundamental neuronal mechanism taking into account the fatigue due to spike emissions and the consequent reduction of the firing activity. We have studied the effect of this adaptation mechanism on the macroscopic dynamics of excitatory and inhibitory networks of quadratic integrate-and-fire (QIF) neurons coupled via exponentially decaying post-synaptic potentials. In particular, we have studied the population activities by employing an exact mean-field reduction, which gives rise to next-generation neural mass models. This low-dimensional reduction allows for the derivation of bifurcation diagrams and the identification of the possible macroscopic regimes emerging both in a single and in two identically coupled neural masses. In single populations SFA favors the emergence of population bursts in excitatory networks, while it hinders tonic population spiking for inhibitory ones. The symmetric coupling of two neural masses, in absence of adaptation, leads to the emergence of macroscopic solutions with broken symmetry, namely, chimera-like solutions in the inhibitory case and antiphase population spikes in the excitatory one. The addition of SFA leads to new collective dynamical regimes exhibiting cross-frequency coupling (CFC) among the fast synaptic timescale and the slow adaptation one, ranging from antiphase slow-fast nested oscillations to symmetric and asymmetric bursting phenomena. The analysis of these CFC rhythms in the θ-γ range has revealed that a reduction of SFA leads to an increase of the θ frequency joined to a decrease of the γ one. This is analogous to what has been reported experimentally for the hippocampus and the olfactory cortex of rodents under cholinergic modulation, which is known to reduce SFA.

Collective excitability in highly diluted random networks of oscillators.

We report on collective excitable events in a highly diluted random network of non-excitable nodes. Excitability arises thanks to a self-sustained local adaptation mechanism that drives the system on a slow timescale across a hysteretic phase transition involving states with different degrees of synchronization. These phenomena have been investigated for the Kuramoto model with bimodal distribution of the natural frequencies and for the Kuramoto model with inertia and a unimodal frequency distribution. We consider global and partial stimulation protocols and characterize the system response for different levels of dilution. We compare the results with those obtained in the fully coupled case showing that such collective phenomena are remarkably robust against network diluteness.

Coherent oscillations in balanced neural networks driven by endogenous fluctuations.

We present a detailed analysis of the dynamical regimes observed in a balanced network of identical quadratic integrate-and-fire neurons with sparse connectivity for homogeneous and heterogeneous in-degree distributions. Depending on the parameter values, either an asynchronous regime or periodic oscillations spontaneously emerge. Numerical simulations are compared with a mean-field model based on a self-consistent Fokker-Planck equation (FPE). The FPE reproduces quite well the asynchronous dynamics in the homogeneous case by either assuming a Poissonian or renewal distribution for the incoming spike trains. An exact self-consistent solution for the mean firing rate obtained in the limit of infinite in-degree allows identifying balanced regimes that can be either mean- or fluctuation-driven. A low-dimensional reduction of the FPE in terms of circular cumulants is also considered. Two cumulants suffice to reproduce the transition scenario observed in the network. The emergence of periodic collective oscillations is well captured both in the homogeneous and heterogeneous setups by the mean-field models upon tuning either the connectivity or the input DC current. In the heterogeneous situation, we analyze also the role of structural heterogeneity.

Asynchronous and Coherent Dynamics in Balanced Excitatory-Inhibitory Spiking Networks.

Dynamic excitatory-inhibitory (E-I) balance is a paradigmatic mechanism invoked to explain the irregular low firing activity observed in the cortex. However, we will show that the E-I balance can be at the origin of other regimes observable in the brain. The analysis is performed by combining extensive simulations of sparse E-I networks composed of N spiking neurons with analytical investigations of low dimensional neural mass models. The bifurcation diagrams, derived for the neural mass model, allow us to classify the possible asynchronous and coherent behaviors emerging in balanced E-I networks with structural heterogeneity for any finite in-degree K. Analytic mean-field (MF) results show that both supra and sub-threshold balanced asynchronous regimes are observable in our system in the limit N >> K >> 1. Due to the heterogeneity, the asynchronous states are characterized at the microscopic level by the splitting of the neurons in to three groups: silent, fluctuation, and mean driven. These features are consistent with experimental observations reported for heterogeneous neural circuits. The coherent rhythms observed in our system can range from periodic and quasi-periodic collective oscillations (COs) to coherent chaos. These rhythms are characterized by regular or irregular temporal fluctuations joined to spatial coherence somehow similar to coherent fluctuations observed in the cortex over multiple spatial scales. The COs can emerge due to two different mechanisms. A first mechanism analogous to the pyramidal-interneuron gamma (PING), usually invoked for the emergence of γ-oscillations. The second mechanism is intimately related to the presence of current fluctuations, which sustain COs characterized by an essentially simultaneous bursting of the two populations. We observe period-doubling cascades involving the PING-like COs finally leading to the appearance of coherent chaos. Fluctuation driven COs are usually observable in our system as quasi-periodic collective motions characterized by two incommensurate frequencies. However, for sufficiently strong current fluctuations these collective rhythms can lock. This represents a novel mechanism of frequency locking in neural populations promoted by intrinsic fluctuations. COs are observable for any finite in-degree K, however, their existence in the limit N >> K >> 1 appears as uncertain.

Reduction Methodology for Fluctuation Driven Population Dynamics.

Lorentzian distributions have been largely employed in statistical mechanics to obtain exact results for heterogeneous systems. Analytic continuation of these results is impossible even for slightly deformed Lorentzian distributions due to the divergence of all the moments (cumulants). We have solved this problem by introducing a "pseudocumulants" expansion. This allows us to develop a reduction methodology for heterogeneous spiking neural networks subject to extrinsic and endogenous fluctuations, thus obtaining a unified mean-field formulation encompassing quenched and dynamical sources of disorder.

Emergent excitability in populations of nonexcitable units.

Population bursts in a large ensemble of coupled elements result from the interplay between the local excitable properties of the nodes and the global network topology. Here, collective excitability and self-sustained bursting oscillations are shown to spontaneously emerge in globally coupled populations of nonexcitable units subject to adaptive coupling. The ingredients to observe collective excitability are the coexistence of states with different degrees of synchronization joined to a global feedback acting, on a slow timescale, against the synchronization (desynchronization) of the oscillators. These regimes are illustrated for two paradigmatic classes of coupled rotators, namely, the Kuramoto model with and without inertia. For the bimodal Kuramoto model we analytically show that the macroscopic evolution originates from the existence of a critical manifold organizing the fast collective dynamics on a slow timescale. Our results provide evidence that adaptation can induce excitability by maintaining a network permanently out of equilibrium.

Exact neural mass model for synaptic-based working memory.

A synaptic theory of Working Memory (WM) has been developed in the last decade as a possible alternative to the persistent spiking paradigm. In this context, we have developed a neural mass model able to reproduce exactly the dynamics of heterogeneous spiking neural networks encompassing realistic cellular mechanisms for short-term synaptic plasticity. This population model reproduces the macroscopic dynamics of the network in terms of the firing rate and the mean membrane potential. The latter quantity allows us to gain insight of the Local Field Potential and electroencephalographic signals measured during WM tasks to characterize the brain activity. More specifically synaptic facilitation and depression integrate each other to efficiently mimic WM operations via either synaptic reactivation or persistent activity. Memory access and loading are related to stimulus-locked transient oscillations followed by a steady-state activity in the ß-γ band, thus resembling what is observed in the cortex during vibrotactile stimuli in humans and object recognition in monkeys. Memory juggling and competition emerge already by loading only two items. However more items can be stored in WM by considering neural architectures composed of multiple excitatory populations and a common inhibitory pool. Memory capacity depends strongly on the presentation rate of the items and it maximizes for an optimal frequency range. In particular we provide an analytic expression for the maximal memory capacity. Furthermore, the mean membrane potential turns out to be a suitable proxy to measure the memory load, analogously to event driven potentials in experiments on humans. Finally we show that the γ power increases with the number of loaded items, as reported in many experiments, while θ and ß power reveal non monotonic behaviours. In particular, ß and γ rhythms are crucially sustained by the inhibitory activity, while the θ rhythm is controlled by excitatory synapses.

Cross frequency coupling in next generation inhibitory neural mass models.

Coupling among neural rhythms is one of the most important mechanisms at the basis of cognitive processes in the brain. In this study, we consider a neural mass model, rigorously obtained from the microscopic dynamics of an inhibitory spiking network with exponential synapses, able to autonomously generate collective oscillations (COs). These oscillations emerge via a super-critical Hopf bifurcation, and their frequencies are controlled by the synaptic time scale, the synaptic coupling, and the excitability of the neural population. Furthermore, we show that two inhibitory populations in a master-slave configuration with different synaptic time scales can display various collective dynamical regimes: damped oscillations toward a stable focus, periodic and quasi-periodic oscillations, and chaos. Finally, when bidirectionally coupled, the two inhibitory populations can exhibit different types of θ-γ cross-frequency couplings (CFCs): phase-phase and phase-amplitude CFC. The coupling between θ and γ COs is enhanced in the presence of an external θ forcing, reminiscent of the type of modulation induced in hippocampal and cortex circuits via optogenetic drive.

Theta-Nested Gamma Oscillations in Next Generation Neural Mass Models.

Theta-nested gamma oscillations have been reported in many areas of the brain and are believed to represent a fundamental mechanism to transfer information across spatial and temporal scales. In a series of recent experiments in vitro it has been possible to replicate with an optogenetic theta frequency stimulation several features of cross-frequency coupling (CFC) among theta and gamma rhythms observed in behaving animals. In order to reproduce the main findings of these experiments we have considered a new class of neural mass models able to reproduce exactly the macroscopic dynamics of spiking neural networks. In this framework, we have examined two set-ups able to support collective gamma oscillations: namely, the pyramidal interneuronal network gamma (PING) and the interneuronal network gamma (ING). In both set-ups we observe the emergence of theta-nested gamma oscillations by driving the system with a sinusoidal theta-forcing in proximity of a Hopf bifurcation. These mixed rhythms always display phase amplitude coupling. However, two different types of nested oscillations can be identified: one characterized by a perfect phase locking between theta and gamma rhythms, corresponding to an overall periodic behavior; another one where the locking is imperfect and the dynamics is quasi-periodic or even chaotic. From our analysis it emerges that the locked states are more frequent in the ING set-up. In agreement with the experiments, we find theta-nested gamma oscillations for forcing frequencies in the range [1:10] Hz, whose amplitudes grow proportionally to the forcing intensity and which are clearly modulated by the theta phase. Furthermore, analogously to the experiments, the gamma power and the frequency of the gamma-power peak increase with the forcing amplitude. At variance with experimental findings, the gamma-power peak does not shift to higher frequencies by increasing the theta frequency. This effect can be obtained, in our model, only by incrementing, at the same time, also the stimulation power. An effect achieved by increasing the amplitude either of the noise or of the forcing term proportionally to the theta frequency. On the basis of our analysis both the PING and the ING mechanism give rise to theta-nested gamma oscillations with almost identical features.

Neural activity of heterogeneous inhibitory spiking networks with delay.

We study a network of spiking neurons with heterogeneous excitabilities connected via inhibitory delayed pulses. For globally coupled systems the increase of the inhibitory coupling reduces the number of firing neurons by following a winner-takes-all mechanism. For sufficiently large transmission delay we observe the emergence of collective oscillations in the system beyond a critical coupling value. Heterogeneity promotes neural inactivation and asynchronous dynamics and its effect can be counteracted by considering longer time delays. In sparse networks, inhibition has the counterintuitive effect of promoting neural reactivation of silent neurons for sufficiently large coupling. In this regime, current fluctuations are on one side responsible for neural firing of subthreshold neurons and on the other side for their desynchronization. Therefore, collective oscillations are present only in a limited range of coupling values, which remains finite in the thermodynamic limit. Out of this range the dynamics is asynchronous and for very large inhibition neurons display a bursting behavior alternating periods of silence with periods where they fire freely in absence of any inhibition.

Internal representation of hippocampal neuronal population spans a time-distance continuum.

The hippocampus plays a critical role in episodic memory: the sequential representation of visited places and experienced events. This function is mirrored by hippocampal activity that self organizes into sequences of neuronal activation that integrate spatiotemporal information. What are the underlying mechanisms of such integration is still unknown. Single cell activity was recently shown to combine time and distance information; however, it remains unknown whether a degree of tuning between space and time can be defined at the network level. Here, combining daily calcium imaging of CA1 sequence dynamics in running head-fixed mice and network modeling, we show that CA1 network activity tends to represent a specific combination of space and time at any given moment, and that the degree of tuning can shift within a continuum from 1 day to the next. Our computational model shows that this shift in tuning can happen under the control of the external drive power. We propose that extrinsic global inputs shape the nature of spatiotemporal integration in the hippocampus at the population level depending on the task at hand, a hypothesis which may guide future experimental studies.

Modeling driver cells in developing neuronal networks.

Spontaneous emergence of synchronized population activity is a characteristic feature of developing brain circuits. Recent experiments in the developing neo-cortex showed the existence of driver cells able to impact the synchronization dynamics when single-handedly stimulated. We have developed a spiking network model capable to reproduce the experimental results, thus identifying two classes of driver cells: functional hubs and low functionally connected (LC) neurons. The functional hubs arranged in a clique orchestrated the synchronization build-up, while the LC drivers were lately or not at all recruited in the synchronization process. Notwithstanding, they were able to alter the network state when stimulated by modifying the temporal activation of the functional clique or even its composition. LC drivers can lead either to higher population synchrony or even to the arrest of population dynamics, upon stimulation. Noticeably, some LC driver can display both effects depending on the received stimulus. We show that in the model the presence of inhibitory neurons together with the assumption that younger cells are more excitable and less connected is crucial for the emergence of LC drivers. These results provide a further understanding of the structural-functional mechanisms underlying synchronized firings in developing circuits possibly related to the coordinated activity of cell assemblies in the adult brain.

Transition from Asynchronous to Oscillatory Dynamics in Balanced Spiking Networks with Instantaneous Synapses.

We report a transition from asynchronous to oscillatory behavior in balanced inhibitory networks for class I and II neurons with instantaneous synapses. Collective oscillations emerge for sufficiently connected networks. Their origin is understood in terms of a recently developed mean-field model, whose stable solution is a focus. Microscopic irregular firings, due to balance, trigger sustained oscillations by exciting the relaxation dynamics towards the macroscopic focus. The same mechanism induces in balanced excitatory-inhibitory networks quasiperiodic collective oscillations.

Ubiquity of collective irregular dynamics in balanced networks of spiking neurons.

We revisit the dynamics of a prototypical model of balanced activity in networks of spiking neurons. A detailed investigation of the thermodynamic limit for fixed density of connections (massive coupling) shows that, when inhibition prevails, the asymptotic regime is not asynchronous but rather characterized by a self-sustained irregular, macroscopic (collective) dynamics. So long as the connectivity is massive, this regime is found in many different setups: leaky as well as quadratic integrate-and-fire neurons; large and small coupling strength; and weak and strong external currents.

Exact firing time statistics of neurons driven by discrete inhibitory noise.

Neurons in the intact brain receive a continuous and irregular synaptic bombardment from excitatory and inhibitory pre- synaptic neurons, which determines the firing activity of the stimulated neuron. In order to investigate the influence of inhibitory stimulation on the firing time statistics, we consider Leaky Integrate-and-Fire neurons subject to inhibitory instantaneous post- synaptic potentials. In particular, we report exact results for the firing rate, the coefficient of variation and the spike train spectrum for various synaptic weight distributions. Our results are not limited to stimulations of infinitesimal amplitude, but they apply as well to finite amplitude post-synaptic potentials, thus being able to capture the effect of rare and large spikes. The developed methods are able to reproduce also the average firing properties of heterogeneous neuronal populations.

Cell Assembly Dynamics of Sparsely-Connected Inhibitory Networks: A Simple Model for the Collective Activity of Striatal Projection Neurons.

Striatal projection neurons form a sparsely-connected inhibitory network, and this arrangement may be essential for the appropriate temporal organization of behavior. Here we show that a simplified, sparse inhibitory network of Leaky-Integrate-and-Fire neurons can reproduce some key features of striatal population activity, as observed in brain slices. In particular we develop a new metric to determine the conditions under which sparse inhibitory networks form anti-correlated cell assemblies with time-varying activity of individual cells. We find that under these conditions the network displays an input-specific sequence of cell assembly switching, that effectively discriminates similar inputs. Our results support the proposal that GABAergic connections between striatal projection neurons allow stimulus-selective, temporally-extended sequential activation of cell assemblies. Furthermore, we help to show how altered intrastriatal GABAergic signaling may produce aberrant network-level information processing in disorders such as Parkinson's and Huntington's diseases.