A dynamical adaptation model of visual spatiotemporal processing in cones and horizontal cells.

In this work, we introduce a phenomenological model for the cone-horizontal cell assembly, including spatial integration and formation of receptive field-like structures. The model extends our previous dynamical adaptation description with gain control accounting for processes in single cones, valid in severe nonlinear regimes. Here, a spatially extended feedback mechanism is introduced from horizontal cells to cones to account for experimental evidence, contributing thus to the development of a center-surround receptive field in cones and downstream bipolar cells. Feedback gain is defined on different spatial scales by weighting spatial filters: a short scale accounting for cone input to the feedback mechanism and a large scale driven by the syncytium characteristics of horizontal cells. A third spatial scale improves the description, mimicking neighboring cone-cone coupling. This overall spatial integration couples to temporal signal processing, thus obtaining a spatiotemporal model of outer retina responses capable of reproducing nonlinear features in both dimensions (space and time). The model was tested and validated using measurements on horizontal cells from different studies, with excellent performance. By its phenomenological nature, signal processing properties are inferred from model parameters. The model can be used in arrays of processing units with more complex incoming patterns of visual stimuli.

Multiscale model of primary motor cortex circuits predicts in vivo cell-type-specific, behavioral state-dependent dynamics.

Understanding cortical function requires studying multiple scales: molecular, cellular, circuit, and behavioral. We develop a multiscale, biophysically detailed model of mouse primary motor cortex (M1) with over 10,000 neurons and 30 million synapses. Neuron types, densities, spatial distributions, morphologies, biophysics, connectivity, and dendritic synapse locations are constrained by experimental data. The model includes long-range inputs from seven thalamic and cortical regions and noradrenergic inputs. Connectivity depends on cell class and cortical depth at sublaminar resolution. The model accurately predicts in vivo layer- and cell-type-specific responses (firing rates and LFP) associated with behavioral states (quiet wakefulness and movement) and experimental manipulations (noradrenaline receptor blockade and thalamus inactivation). We generate mechanistic hypotheses underlying the observed activity and analyzed low-dimensional population latent dynamics. This quantitative theoretical framework can be used to integrate and interpret M1 experimental data and sheds light on the cell-type-specific multiscale dynamics associated with several experimental conditions and behaviors.

Dynamical adaptation in photoreceptors with gain control.

The retina hosts all processes needed to convert external visual stimuli into a neural code. Light phototransduction and its conversion into an electrical signal involve biochemical cascades, ionic regulations, and different kinds of coupling, among other relevant processes. These create a nonlinear processing scheme and light-dependent adaptive responses. The dynamical adaptation model formulated in recent years is an excellent phenomenological candidate to resume all these phenomena into a single feedforward processing scheme. In this work, we analyze this description in highly nonlinear conditions and find that responses do not match those resulting from a very detailed microscopic model, developed to reproduce electrophysiological recordings on horizontal cells. When a delayed light-dependent gain factor incorporates into the description, responses are in excellent agreement, even when spanning several orders of magnitude in light intensity, contrast, and duration, for simple and complex stimuli. This extended model may be instrumental for studies of the retinal function, enabling the linking of the microscopic domain to the understanding of signal processing properties, and further incorporated in spatially extended retinal networks.

Transition to synchronization in heterogeneous inhibitory neural networks with structured synapses.

Inhibitory neurons form an extensive network involved in the development of different rhythms in the cerebral cortex. A transition from an incoherent state, where all inhibitory neurons fire unrelated to each other, to a synchronized or locked state, where all or most neurons define a tight firing pattern, is maybe the most salient process to analyze when considering neuronal rhythms. In this work, we analyzed whether different patterns of effective synaptic connectivity may support a first-order-like transition in this path to synchronization. Such an "explosive" phenomenon may be relevant in neural processes, as normal cognitive processing in different tasks and some neurological disorders manifest an increased power in many neuronal rhythms, supported by an extended concerted spiking activity and an abrupt change to this state. Furthermore, we built an adaptive mechanism that supports the generation of this kind of network, which rapidly creates the underlying structure based on the ongoing firing statistics.

Two types of ictal phase-amplitude couplings in epilepsy patients revealed by spectral harmonicity of intracerebral EEG recordings.

OBJECTIVE: Spectral harmonicity of the ictal activity was analyzed regarding two clinically relevant aspects, (1) as a confounding factor producing 'spurious' phase-amplitude couplings (PAC) which may lead to wrong conclusions about the underlying ictal mechanisms, and (2) its role in how good PAC is in correspondence to the seizure onset zone (SOZ) classification performed by the epileptologists. METHODS: PAC patterns observed in intracerebral electroencephalography (iEEG) recordings were retrospectively studied during seizures of seven patients with pharmacoresistant focal epilepsy. The time locked index (TLI) measure was introduced to quantify the degree of harmonicity between frequency bands associated to the emergence of PAC during epileptic seizures. RESULTS: (1) Harmonic and non harmonic PAC patterns coexist during the seizure dynamics in iEEG recordings with macroelectrodes. (2) Harmonic PAC patterns are an emergent property of the periodic non sinusoidal waveform constituting the epileptiform activity. (3) The TLI metric allows to distinguish the non harmonic PAC pattern, which has been previously associated with the ictal core through the paroxysmal depolarizing shifts mechanism of seizure propagation. CONCLUSIONS: Our results suggest that the spectral harmonicity of the ictal activity plays a relevant role in the visual analysis of the iEEG recordings performed by the epileptologists to define the SOZ, and that it should be considered for the proper interpretation of ictal mechanisms. SIGNIFICANCE: The proposed harmonicity analysis can be used to improve the delineation of the SOZ by reliably identifying non harmonic PAC patterns emerging from fully recruited cortical and subcortical areas.

Complex interplay between spectral harmonicity and different types of cross-frequency couplings in nonlinear oscillators and biologically plausible neural network models.

Cross-frequency coupling (CFC) refers to the nonlinear interaction between oscillations in different frequency bands, and it is a rather ubiquitous phenomenon that has been observed in a variety of physical and biophysical systems. In particular, the coupling between the phase of slow oscillations and the amplitude of fast oscillations, referred as phase-amplitude coupling (PAC), has been intensively explored in the brain activity recorded from animals and humans. However, the interpretation of these CFC patterns remains challenging since harmonic spectral correlations characterizing nonsinusoidal oscillatory dynamics can act as a confounding factor. Specialized signal processing techniques are proposed to address the complex interplay between spectral harmonicity and different types of CFC, not restricted only to PAC. For this, we provide an in-depth characterization of the time locked index (TLI) as a tool aimed to efficiently quantify the harmonic content of noisy time series. It is shown that the proposed TLI measure is more robust and outperforms traditional phase coherence metrics (e.g., phase locking value, pairwise phase consistency) in several aspects. We found that a nonlinear oscillator under the effect of additive noise can produce spurious CFC with low spectral harmonic content. On the other hand, two coupled oscillatory dynamics with independent fundamental frequencies can produce true CFC with high spectral harmonic content via a rectification mechanism or other post-interaction nonlinear processing mechanisms. These results reveal a complex interplay between CFC and harmonicity emerging in the dynamics of biologically plausible neural network models and more generic nonlinear and parametric oscillators. We show that, contrary to what is usually assumed in the literature, the high harmonic content observed in nonsinusoidal oscillatory dynamics is neither a sufficient nor necessary condition to interpret the associated CFC patterns as epiphenomenal. There is mounting evidence suggesting that the combination of multimodal recordings, specialized signal processing techniques, and theoretical modeling is becoming a required step to completely understand CFC patterns observed in oscillatory rich dynamics of physical and biophysical systems.

Partial coherence and frustration in self-organizing spherical grids.

Nearby grid cells have been observed to express a remarkable degree of long-range order, which is often idealized as extending potentially to infinity. Yet their strict periodic firing and ensemble coherence are theoretically possible only in flat environments, much unlike the burrows which rodents usually live in. Are the symmetrical, coherent grid maps inferred in the lab relevant to chart their way in their natural habitat? We consider spheres as simple models of curved environments and waiting for the appropriate experiments to be performed, we use our adaptation model to predict what grid maps would emerge in a network with the same type of recurrent connections, which on the plane produce coherence among the units. We find that on the sphere such connections distort the maps that single grid units would express on their own, and aggregate them into clusters. When remapping to a different spherical environment, units in each cluster maintain only partial coherence, similar to what is observed in disordered materials, such as spin glasses.

Bifurcation structure determines different phase-amplitude coupling patterns in the activity of biologically plausible neural networks.

Phase-amplitude cross frequency coupling (PAC) is a rather ubiquitous phenomenon that has been observed in a variety of physical domains; however, the mechanisms underlying the emergence of PAC and its functional significance in the context of neural processes are open issues under debate. In this work we analytically demonstrate that PAC phenomenon naturally emerges in mean-field models of biologically plausible networks, as a signature of specific bifurcation structures. The proposed analysis, based on bifurcation theory, allows the identification of the mechanisms underlying oscillatory dynamics that are essentially different in the context of PAC. Specifically, we found that two PAC classes can coexist in the complex dynamics of the analyzed networks: 1) harmonic PAC which is an epiphenomenon of the nonsinusoidal waveform shape characterized by the linear superposition of harmonically related spectral components, and 2) nonharmonic PAC associated with "true" coupled oscillatory dynamics with independent frequencies elicited by a secondary Hopf bifurcation and mechanisms involving periodic excitation/inhibition (PEI) of a network population. Importantly, these two PAC types have been experimentally observed in a variety of neural architectures confounding traditional parametric and nonparametric PAC metrics, like those based on linear filtering or the waveform shape analysis, due to the fact that these methods operate on a single one-dimensional projection of an intrinsically multidimensional system dynamics. We exploit the proposed tools to study the functional significance of the PAC phenomenon in the context of Parkinson's disease (PD). Our results show that pathological slow oscillations (e.g. ß band) and nonharmonic PAC patterns emerge from dissimilar underlying mechanisms (bifurcations) and are associated to the competition of different BG-thalamocortical loops. Thus, this study provides theoretical arguments that demonstrate that nonharmonic PAC is not an epiphenomenon related to the pathological ß band oscillations, thus supporting the experimental evidence about the relevance of PAC as a potential biomarker of PD.

Selforganization of modular activity of grid cells.

A unique topographical representation of space is found in the concerted activity of grid cells in the rodent medial entorhinal cortex. Many among the principal cells in this region exhibit a hexagonal firing pattern, in which each cell expresses its own set of place fields (spatial phases) at the vertices of a triangular grid, the spacing and orientation of which are typically shared with neighboring cells. Grid spacing, in particular, has been found to increase along the dorso-ventral axis of the entorhinal cortex but in discrete steps, that is, with a modular structure. In this study, we show that such a modular activity may result from the self-organization of interacting units, which individually would not show discrete but rather continuously varying grid spacing. Within our "adaptation" network model, the effect of a continuously varying time constant, which determines grid spacing in the isolated cell model, is modulated by recurrent collateral connections, which tend to produce a few subnetworks, akin to magnetic domains, each with its own grid spacing. In agreement with experimental evidence, the modular structure is tightly defined by grid spacing, but also involves grid orientation and distortion, due to interactions across modules. Thus, our study sheds light onto a possible mechanism, other than simply assuming separate networks a priori, underlying the formation of modular grid representations.

Can rodents conceive hyperbolic spaces?

The grid cells discovered in the rodent medial entorhinal cortex have been proposed to provide a metric for Euclidean space, possibly even hardwired in the embryo. Yet, one class of models describing the formation of grid unit selectivity is entirely based on developmental self-organization, and as such it predicts that the metric it expresses should reflect the environment to which the animal has adapted. We show that, according to self-organizing models, if raised in a non-Euclidean hyperbolic cage rats should be able to form hyperbolic grids. For a given range of grid spacing relative to the radius of negative curvature of the hyperbolic surface, such grids are predicted to appear as multi-peaked firing maps, in which each peak has seven neighbours instead of the Euclidean six, a prediction that can be tested in experiments. We thus demonstrate that a useful universal neuronal metric, in the sense of a multi-scale ruler and compass that remain unaltered when changing environments, can be extended to other than the standard Euclidean plane.

Effects of spike-triggered negative feedback on receptive-field properties.

Sensory neurons are often described in terms of a receptive field, that is, a linear kernel through which stimuli are filtered before they are further processed. If information transmission is assumed to proceed in a feedforward cascade, the receptive field may be interpreted as the external stimulus' profile maximizing neuronal output. The nervous system, however, contains many feedback loops, and sensory neurons filter more currents than the ones representing the transduced external stimulus. Some of the additional currents are generated by the output activity of the neuron itself, and therefore constitute feedback signals. By means of a time-frequency analysis of the input/output transformation, here we show how feedback modifies the receptive field. The model is applicable to various types of feedback processes, from spike-triggered intrinsic conductances to inhibitory synaptic inputs from nearby neurons. We distinguish between the intrinsic receptive field (filtering all input currents) and the effective receptive field (filtering only external stimuli). Whereas the intrinsic receptive field summarizes the biophysical properties of the neuron associated to subthreshold integration and spike generation, only the effective receptive field can be interpreted as the external stimulus' profile maximizing neuronal output. We demonstrate that spike-triggered feedback shifts low-pass filtering towards band-pass processing, transforming integrator neurons into resonators. For strong feedback, a sharp resonance in the spectral neuronal selectivity may appear. Our results provide a unified framework to interpret a collection of previous experimental studies where specific feedback mechanisms were shown to modify the filtering properties of neurons.

Onset of negative interspike interval correlations in adapting neurons.

Negative serial correlations in single spike trains are an effective method to reduce the variability of spike counts. One of the factors contributing to the development of negative correlations between successive interspike intervals is the presence of adaptation currents. In this work, based on a hidden Markov model and a proper statistical description of conditional responses, we obtain analytically these correlations in an adequate dynamical neuron model resembling adaptation. We derive the serial correlation coefficients for arbitrary lags, under a small adaptation scenario. In this case, the behavior of correlations is universal and depends on the first-order statistical description of an exponentially driven time-inhomogeneous stochastic process.

Survival probability and first-passage-time statistics of a Wiener process driven by an exponential time-dependent drift.

The survival probability and the first-passage-time statistics are important quantities in different fields. The Wiener process is the simplest stochastic process with continuous variables, and important results can be explicitly found from it. The presence of a constant drift does not modify its simplicity; however, when the process has a time-dependent component the analysis becomes difficult. In this work we analyze the statistical properties of the Wiener process with an absorbing boundary, under the effect of an exponential time-dependent drift. Based on the backward Fokker-Planck formalism we set the time-inhomogeneous equation and conditions that rule the diffusion of the corresponding survival probability. We propose as the solution an expansion series in terms of the intensity of the exponential drift, resulting in a set of recurrence equations. We explicitly solve the expansion up to second order and comment on higher-order solutions. The first-passage-time density function arises naturally from the survival probability and preserves the proposed expansion. Explicit results, related properties, and limit behaviors are analyzed and extensively compared to numerical simulations.

The firing statistics of Poisson neuron models driven by slow stimuli.

The coding properties of cells with different types of receptive fields have been studied for decades. ON-type neurons fire in response to positive fluctuations of the time-dependent stimulus, whereas OFF cells are driven by negative stimulus segments. Biphasic cells, in turn, are selective to up/down or down/up stimulus upstrokes. In this article, we explore the way in which different receptive fields affect the firing statistics of Poisson neuron models, when driven with slow stimuli. We find analytical expressions for the time-dependent peri-stimulus time histogram and the inter-spike interval distribution in terms of the incoming signal. Our results enable us to understand the interplay between the intrinsic and extrinsic factors that regulate the statistics of spike trains. The former depend on biophysical neural properties, whereas the latter hinge on the temporal characteristics of the input signal.

Quasistatic approximation of the interspike interval distribution of neurons driven by time-dependent inputs.

Variability in neural responses is a ubiquitous phenomenon in neurons, usually modeled with stochastic differential equations. In particular, stochastic integrate-and-fire models are widely used to simplify theoretical studies. The statistical properties of the generated spikes depend on the stimulating input current. Given that real sensory neurons are driven by time-dependent signals, here we study how the interspike interval distribution of integrate-and-fire neurons depends on the evolution of the stimulus in a quasistatic limit. We obtain a closed-form expression for this distribution, and we compare it to the one obtained with numerical simulations for several time-dependent currents. For slow inputs, the quasistatic distribution provides a very good description of the data. The results obtained for the integrate-and-fire model can be extended to other nonautonomous stochastic systems where the first passage time problem has an explicit solution.