Amir Goldental

Neuronal response impedance mechanism implementing cooperative networks with low firing rates and μs precision

Realizations of low firing rates in neural networks usually require globally balanced distributions among excitatory and inhibitory links, while feasibility of temporal coding is limited by neuronal millisecond precision. We show that cooperation, governing global network features, emerges through nodal properties, as opposed to link distributions. Using in vitro and in vivo experiments we demonstrate microsecond precision of neuronal response timings under low stimulation frequencies, whereas moderate frequencies result in a chaotic neuronal phase characterized by degraded precision. Above a critical stimulation frequency, which varies among neurons, response failures were found to emerge stochastically such that the neuron functions as a low pass filter, saturating the average inter-spike-interval. This intrinsic neuronal response impedance mechanism leads to cooperation on a network level, such that firing rates are suppressed toward the lowest neuronal critical frequency simultaneously with neuronal microsecond precision. Our findings open up opportunities of controlling global features of network dynamics through few nodes with extreme properties.

Simultaneous multi-patch-clamp and extracellular-array recordings: Single neuron reflects network activity

The increasing number of recording electrodes enhances the capability of capturing the network’s cooperative activity, however, using too many monitors might alter the properties of the measured neural network and induce noise. Using a technique that merges simultaneous multi-patch-clamp and multi-electrode array recordings of neural networks in-vitro, we show that the membrane potential of a single neuron is a reliable and super-sensitive probe for monitoring such cooperative activities and their detailed rhythms. Specifically, the membrane potential and the spiking activity of a single neuron are either highly correlated or highly anti-correlated with the time-dependent macroscopic activity of the entire network. This surprising observation also sheds light on the cooperative origin of neuronal burst in cultured networks. Our findings present an alternative flexible approach to the technique based on a massive tiling of networks by large-scale arrays of electrodes to monitor their activity.

A computational paradigm for dynamic logic-gates in neuronal activity.

In 1943 McCulloch and Pitts suggested that the brain is composed of reliable logic-gates similar to the logic at the core of todays computers. This framework had a limited impact on neuroscience, since neurons exhibit far richer dynamics. Here we propose a new experimentally corroborated paradigm in which the truth tables of the brains logic-gates are time dependent, i.e., dynamic logic-gates (DLGs). The truth tables of the DLGs depend on the history of their activity and the stimulation frequencies of their input neurons. Our experimental results are based on a procedure where conditioned stimulations were enforced on circuits of neurons embedded within a large-scale network of cortical cells in-vitro. We demonstrate that the underlying biological mechanism is the unavoidable increase of neuronal response latencies to ongoing stimulations, which imposes a non-uniform gradual stretching of network delays. The limited experimental results are confirmed and extended by simulations and theoretical arguments based on identical neurons with a fixed increase of the neuronal response latency per evoked spike. We anticipate our results to lead to better understanding of the suitability of this computational paradigm to account for the brains functionalities and will require the development of new systematic mathematical methods beyond the methods developed for traditional Boolean algebra.

Broadband Macroscopic Cortical Oscillations Emerge from Intrinsic Neuronal Response Failures

Broadband spontaneous macroscopic neural oscillations are rhythmic cortical firing which were extensively examined during the last century, however, their possible origination is still controversial. In this work we show how macroscopic oscillations emerge in solely excitatory random networks and without topological constraints. We experimentally and theoretically show that these oscillations stem from the counterintuitive underlying mechanism—the intrinsic stochastic neuronal response failures (NRFs). These NRFs, which are characterized by short-term memory, lead to cooperation among neurons, resulting in sub- or several- Hertz macroscopic oscillations which coexist with high frequency gamma oscillations. A quantitative interplay between the statistical network properties and the emerging oscillations is supported by simulations of large networks based on single-neuron in-vitro experiments and a Langevin equation describing the network dynamics. Results call for the examination of these oscillations in the presence of inhibition and external drives.

An experimental evidence-based computational paradigm for new logic-gates in neuronal activity

We propose a new experimentally corroborated paradigm in which the functionality of the brains logic-gates depends on the history of their activity, e.g. an OR-gate that turns into a XOR-gate over time. Our results are based on an experimental procedure where conditioned stimulations were enforced on circuits of neurons embedded within a large-scale network of cortical cells in vitro. The underlying biological mechanism is the unavoidable increase of neuronal response latency to ongoing stimulations, which imposes a non-uniform gradual stretching of network delays.

New Types of Experiments Reveal that a Neuron Functions as Multiple Independent Threshold Units

Neurons are the computational elements that compose the brain and their fundamental principles of activity are known for decades. According to the long-lasting computational scheme, each neuron sums the incoming electrical signals via its dendrites and when the membrane potential reaches a certain threshold the neuron typically generates a spike to its axon. Here we present three types of experiments, using neuronal cultures, indicating that each neuron functions as a collection of independent threshold units. The neuron is anisotropically activated following the origin of the arriving signals to the membrane, via its dendritic trees. The first type of experiments demonstrates that a single neuron’s spike waveform typically varies as a function of the stimulation location. The second type reveals that spatial summation is absent for extracellular stimulations from different directions. The third type indicates that spatial summation and subtraction are not achieved when combining intra- and extra- cellular stimulations, as well as for nonlocal time interference, where the precise timings of the stimulations are irrelevant. Results call to re-examine neuronal functionalities beyond the traditional framework, and the advanced computational capabilities and dynamical properties of such complex systems.

Sudden synchrony leaps accompanied by frequency multiplications in neuronal activity

A classical view of neural coding relies on temporal firing synchrony among functional groups of neurons, however, the underlying mechanism remains an enigma. Here we experimentally demonstrate a mechanism where time-lags among neuronal spiking leap from several tens of milliseconds to nearly zero-lag synchrony. It also allows sudden leaps out of synchrony, hence forming short epochs of synchrony. Our results are based on an experimental procedure where conditioned stimulations were enforced on circuits of neurons embedded within a large-scale network of cortical cells in vitro and are corroborated by simulations of neuronal populations. The underlying biological mechanisms are the unavoidable increase of the neuronal response latency to ongoing stimulations and temporal or spatial summation required to generate evoked spikes. These sudden leaps in and out of synchrony may be accompanied by multiplications of the neuronal firing frequency, hence offering reliable information-bearing indicators which may bridge between the two principal neuronal coding paradigms.

Vitality of Neural Networks under Reoccurring Catastrophic Failures.

Catastrophic failures are complete and sudden collapses in the activity of large networks such as economics, electrical power grids and computer networks, which typically require a manual recovery process. Here we experimentally show that excitatory neural networks are governed by a non-Poissonian reoccurrence of catastrophic failures, where their repetition time follows a multimodal distribution characterized by a few tenths of a second and tens of seconds timescales. The mechanism underlying the termination and reappearance of network activity is quantitatively shown here to be associated with nodal time-dependent features, neuronal plasticity, where hyperactive nodes damage the response capability of their neighbors. It presents a complementary mechanism for the emergence of Poissonian catastrophic failures from damage conductivity. The effect that hyperactive nodes degenerate their neighbors represents a type of local competition which is a common feature in the dynamics of real-world complex networks, whereas their spontaneous recoveries represent a vitality which enhances reliable functionality.

Adaptive nodes enrich nonlinear cooperative learning beyond traditional adaptation by links

Physical models typically assume time-independent interactions, whereas neural networks and machine learning incorporate interactions that function as adjustable parameters. Here we demonstrate a new type of abundant cooperative nonlinear dynamics where learning is attributed solely to the nodes, instead of the network links which their number is significantly larger. The nodal, neuronal, fast adaptation follows its relative anisotropic (dendritic) input timings, as indicated experimentally, similarly to the slow learning mechanism currently attributed to the links, synapses. It represents a non-local learning rule, where effectively many incoming links to a node concurrently undergo the same adaptation. The network dynamics is now counterintuitively governed by the weak links, which previously were assumed to be insignificant. This cooperative nonlinear dynamic adaptation presents a self-controlled mechanism to prevent divergence or vanishing of the learning parameters, as opposed to learning by links, and also supports self-oscillations of the effective learning parameters. It hints on a hierarchical computational complexity of nodes, following their number of anisotropic inputs and opens new horizons for advanced deep learning algorithms and artificial intelligence based applications, as well as a new mechanism for enhanced and fast learning by neural networks.

Fast reversible learning based on neurons functioning as anisotropic multiplex hubs

Neural networks are composed of neurons and synapses, which are responsible for learning in a slow adaptive dynamical process. Here we experimentally show that neurons act like independent anisotropic multiplex hubs, which relay and mute incoming signals following their input directions. Theoretically, the observed information routing enriches the computational capabilities of neurons by allowing, for instance, equalization among different information routes in the network, as well as high-frequency transmission of complex time-dependent signals constructed via several parallel routes. In addition, this kind of hubs adaptively eliminate very noisy neurons from the dynamics of the network, preventing masking of information transmission. The timescales for these features are several seconds at most, as opposed to the imprint of information by the synaptic plasticity, a process which exceeds minutes. Results open the horizon to the understanding of fast and adaptive learning realities in higher cognitive functionalities of the brain.