Neural Circuit Model Research Articles

Synaptic basis of a sub-second representation of time in a neural circuit model

Temporal sequences of neural activity are essential for driving well-timed behaviors, but the underlying cellular and circuit mechanisms remain elusive. We leveraged the well-defined architecture of the cerebellum, a brain region known to support temporally precise actions, to explore theoretically whether the experimentally observed diversity of short-term synaptic plasticity (STP) at the input layer could generate neural dynamics sufficient for sub-second temporal learning. A cerebellar circuit model equipped with dynamic synapses produced a diverse set of transient granule cell firing patterns that provided a temporal basis set for learning precisely timed pauses in Purkinje cell activity during simulated delay eyelid conditioning and Bayesian interval estimation. The learning performance across time intervals was influenced by the temporal bandwidth of the temporal basis, which was determined by the input layer synaptic properties. The ubiquity of STP throughout the brain positions it as a general, tunable cellular mechanism for sculpting neural dynamics and fine-tuning behavior.

An intrinsic oscillator underlies visual navigation in ants

Many insects display lateral oscillations while moving, but how these oscillations are produced and participate in visual navigation remains unclear. Here, we show that visually navigating ants continuously display regular lateral oscillations coupled with variations of forward speed that strongly optimize the distance covered while simultaneously enabling them to scan left and right directions. This pattern of movement is produced endogenously and conserved across navigational contexts in two phylogenetically distant ant species. Moreover, the oscillations' amplitude can be modulated by both innate or learnt visual cues to adjust the exploration/exploitation balance to the current need. This lower-level motor pattern thus drastically reduces the degree of freedom needed for higher-level strategies to control behavior. The observed dynamical signature readily emerges from a simple neural circuit model of the insect's conserved pre-motor area known as the lateral accessory lobe, offering a surprisingly simple but effective neural control and endorsing oscillation as a core, ancestral way of moving in insects.

Recurrent neural circuits for perceptual grouping

Neurons in the visual cortex are sensitive to context: Responses to stimuli presented within their classical receptive fields (CRFs) are modulated by stimuli in their surrounding extra-classical receptive fields (eCRFs). However, the circuits underlying these contextual effects are not well understood, and little is known about how these circuits drive perception during everyday vision. We tackle these questions by approximating circuit-level eCRF models with a differentiable discrete-time recurrent neural network that is trainable with gradient-descent. After optimizing model synaptic connectivity and dynamics for object contour detection in natural images, the neural-circuit model rivals human observers on the task with far better sample efficiency than state-of-the-art computer vision approaches. Notably, the model also exhibits CRF and eCRF phenomena typically associated with primate vision. The model’s ability to accurately detect object contours also critically depends on these effects, and these contextual effects are not found in ablated versions of the model. Finally, we derive testable predictions about the neural mechanisms responsible for contextual integration and illustrate their importance for accurate and efficient perceptual grouping.

Simulation of oscillatory dynamics induced by an approximation of grid cell output.

Grid cells, in entorhinal cortex (EC) and related structures, signal animal location relative to hexagonal tilings of 2D space. A number of modeling papers have addressed the question of how grid firing behaviors emerge using (for example) ideas borrowed from dynamical systems (attractors) or from coupled oscillator theory. Here weuse a different approach: instead of asking howgrid behavior emerges, we take as a given the experimentally observed intracellular potentials of superficial medial EC neurons during grid firing. Employing a detailed neural circuit model modified from a lateral ECmodel, we then askhow the circuit responds when group of medial EC principal neurons exhibit such potentials, simultaneously with a simulated theta frequency input from the septal nuclei. The model predicts the emergence of robust theta-modulated gamma/beta oscillations, suggestive of oscillations observed in an in vitro medial EC experimental model (Cunningham, M.O., Pervouchine, D.D., Racca, C., Kopell, N.J., Davies, C.H., Jones, R.S.G., Traub, R.D., and Whittington, M.A. (2006). Neuronal metabolism governs cortical network response state. Proc. Natl. Acad. Sci. U S A 103: 5597-5601). Such oscillations result because feedback interneurons tightly synchronize with each other- despite the varying phases of the grid cells- and generate a robust inhibition-based rhythm. The lack of spatial specificity of the model interneurons is consistent with the lack of spatial periodicity in parvalbumin interneurons observed by Buetfering, C., Allen, K., and Monyer, H. (2014). Parvalbumin interneurons provide gridcell-driven recurrent inhibition in the medial entorhinal cortex. Nat. Neurosci. 17: 710-718. If in vivo EC gamma rhythms arise during exploration as our model predicts, there could be implications for interpreting disrupted spatial behavior and gamma oscillations in animal models of Alzheimer's disease and schizophrenia. Noting that experimental intracellular grid cell potentials closely resemble cortical Up states and Down states, during which fast oscillations also occur during Up states, we propose that the co-occurrence of slow principal celldepolarizations and fast network oscillations is a generalproperty of the telencephalon, in both waking andsleep states.

Neural Ordinary Differential Equation Models of Circuits: Capabilities and Pitfalls

This work advances the application of neural ordinary differential equations (ODEs) to circuit modeling. Prior works primarily utilized the recurrent neural network (RNN), which is a specific type of neural ODE. In this work, the capability of neural ODEs to represent different types of circuits is studied. Stability conditions are presented, both for neural ODEs in a standalone configuration and for neural ODEs with feedback connections, and practical techniques to impose the stability constraints during training are demonstrated. Based on the theoretical and experimental results, this work provides guidance as to when and how an accurate and stable neural ODE circuit model can be generated.

How to incorporate biological insights into network models and why it matters.

Due to the staggering complexity of the brain and its neural circuitry, neuroscientists rely on the analysis of mathematical models to elucidate its function. From Hodgkin and Huxley's detailed description of the action potential in 1952 to today, new theories and increasing computational power have opened up novel avenues to study how neural circuits implement the computations that underlie behaviour. Computational neuroscientists have developed many models of neural circuits that differ in complexity, biological realism or emergent network properties. With recent advances in experimental techniques for detailed anatomical reconstructions or large-scale activity recordings, richbiological data have become more available. The challenge when building network models is to reflect experimental results, either through a high level of detail or by finding an appropriate level of abstraction. Meanwhile, machine learning has facilitated the development of artificial neural networks, which are trained to perform specific tasks. While they have proven successful at achieving task-oriented behaviour, they are often abstract constructs that differ in many features from the physiology of brain circuits. Thus, it is unclear whether the mechanisms underlying computation in biological circuits can be investigated by analysing artificial networks that accomplish the same function but differ in their mechanisms. Here, we argue that building biologically realistic network models is crucial to establishing causal relationships between neurons, synapses, circuits and behaviour. More specifically, we advocate for network models that consider the connectivity structure and the recorded activity dynamics while evaluating task performance.

Computational model predicts the neural mechanisms of prepulse inhibition in Drosophila larvae

Prepulse inhibition (PPI) is a behavioural phenomenon in which a preceding weaker stimulus suppresses the startle response to a subsequent stimulus. The effect of PPI has been found to be reduced in psychiatric patients and is a promising neurophysiological indicator of psychiatric disorders. Because the neural circuit of the startle response has been identified at the cellular level, investigating the mechanism underlying PPI in Drosophila melanogaster larvae through experiment-based mathematical modelling can provide valuable insights. We recently identified PPI in Drosophila larvae and found that PPI was reduced in larvae mutated with the Centaurin gamma 1A (CenG1A) gene, which may be associated with autism. In this study, we used numerical simulations to investigate the neural mechanisms underlying PPI in Drosophila larvae. We adjusted the parameters of a previously developed Drosophila larvae computational model and demonstrated that the model could reproduce several behaviours, including PPI. An analysis of the temporal changes in neuronal activity when PPI occurs using our neural circuit model suggested that the activity of specific neurons triggered by prepulses has a considerable effect on PPI. Furthermore, we validated our speculations on PPI reduction in CenG1A mutants with simulations.

Advances in construction and modeling of functional neural circuits in vitro

Over the years, techniques have been developed to culture and assemble neurons, which brought us closer to creating neuronal circuits that functionally and structurally mimic parts of the brain. Starting with primary culture of neurons, preparations of neuronal culture have advanced substantially. Development of stem cell research and brain organoids has opened a new path for generating three-dimensional human neural circuits. Along with the progress in biology, engineering technologies advanced and paved the way for construction of neural circuit structures. In this article, we overview research progress and discuss perspective of in vitro neural circuits and their ability and potential to acquire functions. Construction of in vitro neural circuits with complex higher-order functions would be achieved by converging development in diverse major disciplines including neuroscience, stem cell biology, tissue engineering, electrical engineering and computer science.

Inputs to the Sleep Homeostat Originate Outside the Brain.

The need to sleep is sensed and discharged in a poorly understood process that is homeostatically controlled over time. In flies, different contributions to this process have been attributed to peripheral ppk and central brain neurons, with the former serving as hypothetical inputs to the sleep homeostat and the latter reportedly serving as the homeostat itself. Here we re-evaluate these distinctions in light of new findings using female flies. First, activating neurons targeted by published ppk and brain drivers elicits similar phenotypes, namely, sleep deprivation followed by rebound sleep. Second, inhibiting activity or synaptic output with one type of driver suppresses sleep homeostasis induced using the other type of driver. Third, drivers previously used to implicate central neurons in sleep homeostasis unexpectedly also label ppk neurons. Fourth, activating only this subset of colabeled neurons is sufficient to elicit sleep homeostasis. Thus, many published contributions of central neurons to sleep homeostasis can be explained by previously unrecognized expression of brain drivers in peripheral ppk neurons, most likely those in the legs, which promote walking. Last, we show that activation of certain non-ppk neurons can also induce sleep homeostasis. Notably, axons of these as well as ppk neurons terminate in the same ventral brain region, suggesting that a previously undefined neural circuit element of a sleep homeostat may lie nearby.SIGNIFICANCE STATEMENT The biological needs that sleep fulfills are unknown, but they are reflected by the ability of an animal to compensate for prior sleep loss in a process called sleep homeostasis. Researchers have searched for the neural circuitry that comprises the sleep homeostat so that the information it conveys can shed light on the nature of sleep need. Here we demonstrate that neurons originating outside of the brain are responsible for phenotypes previously attributed to the proposed central brain sleep homeostat in flies. Our results support a revised neural circuit model for sensing and discharging sleep need in which peripheral inputs connect to a sleep homeostat through previously unrecognized neural circuit elements in the ventral brain.

Ipsilateral and Contralateral Interactions in Spinal Locomotor Circuits Mediated by V1 Neurons: Insights from Computational Modeling.

We describe and analyze a computational model of neural circuits in the mammalian spinal cord responsible for generating and shaping locomotor-like oscillations. The model represents interacting populations of spinal neurons, including the neurons that were genetically identified and characterized in a series of previous experimental studies. Here, we specifically focus on the ipsilaterally projecting V1 interneurons, their possible role in the spinal locomotor circuitry, and their involvement in the generation of locomotor oscillations. The proposed connections of these neurons and their involvement in different neuronal pathways in the spinal cord allow the model to reproduce the results of optogenetic manipulations of these neurons under different experimental conditions. We suggest the existence of two distinct populations of V1 interneurons mediating different ipsilateral and contralateral interactions within the spinal cord. The model proposes explanations for multiple experimental data concerning the effects of optogenetic silencing and activation of V1 interneurons on the frequency of locomotor oscillations in the intact cord and hemicord under different experimental conditions. Our simulations provide an important insight into the organization of locomotor circuitry in the mammalian spinal cord.

A spatiotemporal mechanism of visual attention: Superdiffusive motion and theta oscillations of neural population activity patterns

Recent evidence has demonstrated that during visual spatial attention sampling, neural activity and behavioral performance exhibit large fluctuations. To understand the origin of these fluctuations and their functional role, here, we introduce a mechanism based on the dynamical activity pattern (attention spotlight) emerging from neural circuit models in the transition regime between different dynamical states. This attention activity pattern with rich spatiotemporal dynamics flexibly samples from different stimulus locations, explaining many key aspects of temporal fluctuations such as variable theta oscillations of visual spatial attention. Moreover, the mechanism expands our understanding of how visual attention exploits spatially complex fluctuations characterized by superdiffusive motion in space and makes experimentally testable predictions. We further illustrate that attention sampling based on such spatiotemporal fluctuations provides profound functional advantages such as adaptive switching between exploitation and exploration activities and is particularly efficient at sampling natural scenes with multiple salient objects.

Reinforcement Learning for Central Pattern Generation in Dynamical Recurrent Neural Networks.

Lifetime learning, or the change (or acquisition) of behaviors during a lifetime, based on experience, is a hallmark of living organisms. Multiple mechanisms may be involved, but biological neural circuits have repeatedly demonstrated a vital role in the learning process. These neural circuits are recurrent, dynamic, and non-linear and models of neural circuits employed in neuroscience and neuroethology tend to involve, accordingly, continuous-time, non-linear, and recurrently interconnected components. Currently, the main approach for finding configurations of dynamical recurrent neural networks that demonstrate behaviors of interest is using stochastic search techniques, such as evolutionary algorithms. In an evolutionary algorithm, these dynamic recurrent neural networks are evolved to perform the behavior over multiple generations, through selection, inheritance, and mutation, across a population of solutions. Although, these systems can be evolved to exhibit lifetime learning behavior, there are no explicit rules built into these dynamic recurrent neural networks that facilitate learning during their lifetime (e.g., reward signals). In this work, we examine a biologically plausible lifetime learning mechanism for dynamical recurrent neural networks. We focus on a recently proposed reinforcement learning mechanism inspired by neuromodulatory reward signals and ongoing fluctuations in synaptic strengths. Specifically, we extend one of the best-studied and most-commonly used dynamic recurrent neural networks to incorporate the reinforcement learning mechanism. First, we demonstrate that this extended dynamical system (model and learning mechanism) can autonomously learn to perform a central pattern generation task. Second, we compare the robustness and efficiency of the reinforcement learning rules in relation to two baseline models, a random walk and a hill-climbing walk through parameter space. Third, we systematically study the effect of the different meta-parameters of the learning mechanism on the behavioral learning performance. Finally, we report on preliminary results exploring the generality and scalability of this learning mechanism for dynamical neural networks as well as directions for future work.

Bridging physiological and perceptual views of autism by means of sampling-based Bayesian inference.

Theories for autism spectrum disorder (ASD) have been formulated at different levels, ranging from physiological observations to perceptual and behavioral descriptions. Understanding the physiological underpinnings of perceptual traits in ASD remains a significant challenge in the field. Here we show how a recurrent neural circuit model that was optimized to perform sampling-based inference and displays characteristic features of cortical dynamics can help bridge this gap. The model was able to establish a mechanistic link between two descriptive levels for ASD: a physiological level, in terms of inhibitory dysfunction, neural variability, and oscillations, and a perceptual level, in terms of hypopriors in Bayesian computations. We took two parallel paths-inducing hypopriors in the probabilistic model, and an inhibitory dysfunction in the network model-which lead to consistent results in terms of the represented posteriors, providing support for the view that both descriptions might constitute two sides of the same coin.

Connectomics: Relating synaptic connectivity to physiology

Synaptic wiring diagrams, or connectomes, promise constraints for highly detailed neural circuit models, but relating the connectivity information they provide to physiological properties is challenging. A new study describes this relationship for a fruit fly neural pathway, suggesting a path forward for future models.

Premature commitment to uncertain decisions during human NMDA receptor hypofunction

Making accurate decisions based on unreliable sensory evidence requires cognitive inference. Dysfunction of n-methyl-d-aspartate (NMDA) receptors impairs the integration of noisy input in theoretical models of neural circuits, but whether and how this synaptic alteration impairs human inference and confidence during uncertain decisions remains unknown. Here we use placebo-controlled infusions of ketamine to characterize the causal effect of human NMDA receptor hypofunction on cognitive inference and its neural correlates. At the behavioral level, ketamine triggers inference errors and elevated decision uncertainty. At the neural level, ketamine is associated with imbalanced coding of evidence and premature response preparation in electroencephalographic (EEG) activity. Through computational modeling of inference and confidence, we propose that this specific pattern of behavioral and neural impairments reflects an early commitment to inaccurate decisions, which aims at resolving the abnormal uncertainty generated by NMDA receptor hypofunction.

A Physically Inspired Equivalent Neural Network Circuit Model for SoC Estimation of Electrochemical Cells

Battery Management System (BMS) design for Lithium-ion batteries State of Charge (SoC) prediction has a crucial role in Electric Vehicles (EVs) and smart grids development. The need to design compact, light and fast devices requires finding a suitable trade-off between effectiveness and efficiency. In the literature, it is well emphasized that the application of electrochemical-based methods such as the Pseudo-Two-Dimensional (P2D) model is computationally prohibitive and requires significant simplifications. Conversely, plain Equivalent Circuit Models (ECM) are too simple and unable to represent the cell dynamics. The application of an Ensemble Neural Network (ENN) as Equivalent Neural Network Circuit (ENNC) emerged as a promising solution able to synthesize expressive and computationally efficient models. Indeed, with the support of a suitable dataset, an ENN can be configured to represent a given ECM, modeling each lumped parameter through an assigned Neural Network (NN). Accordingly, the ENNC system is able to keep a physical description of the battery cell while approximating the non-linear dynamic of each component. The paper proposes a novel ENNC battery named Physical Inspired-Equivalent Neural Network Circuit (PI-ENNC) whose ensemble architecture relies on a fractional-order Extended Single Particle (ESP) Lithium-ion cell formulation. The PI-ENNC is designed to approximate the ESP transfer functions referred to the ohmic effects, the electrolyte diffusion and the non-uniform charge distribution in the cell. The proposed model has been tested with three publicly available datasets, investigating the model behavior according to two different training strategies and with different input configurations. In order to prove its effectiveness, results have been compared with a simpler version proposed in a previous work. Results highlight the effectiveness of PI-ENNC in SoC prediction, underlining the importance of designing an ENN architecture that leverages on equations and constraints that reflect the physical phenomena of the cell.

Edge to quantum: hybrid quantum-spiking neural network image classifier

The extreme parallelism property warrant convergence of neural networks with that of quantum computing. As the size of the network grows, the classical implementation of neural networks becomes computationally expensive and not feasible. In this paper, we propose a hybrid image classifier model using spiking neural networks (SNN) and quantum circuits that combines dynamic behaviour of SNN with the extreme parallelism offered by quantum computing. The proposed model outperforms models in comparison with spiking neural network in classical computing, and hybrid convolution neural network-quantum circuit models in terms of various performance parameters. The proposed hybrid SNN-QC model achieves an accuracy of 99.9% in comparison with CNN-QC model accuracy of 96.3%, and SNN model of accuracy 91.2% in MNIST classification task. The tests on KMNIST and CIFAR-1O also showed improvements.

Model-based prediction of muscarinic receptor function from auditory mismatch negativity responses

Drugs affecting neuromodulation, for example by dopamine or acetylcholine, take centre stage among therapeutic strategies in psychiatry. These neuromodulators can change both neuronal gain and synaptic plasticity and therefore affect electrophysiological measures. An important goal for clinical diagnostics is to exploit this effect in the reverse direction, i.e., to infer the status of specific neuromodulatory systems from electrophysiological measures.In this study, we provide proof-of-concept that the functional status of cholinergic (specifically muscarinic) receptors can be inferred from electrophysiological data using generative (dynamic causal) models. To this end, we used epidural EEG recordings over two auditory cortical regions during a mismatch negativity (MMN) paradigm in rats. All animals were treated, across sessions, with muscarinic receptor agonists and antagonists at different doses. Together with a placebo condition, this resulted in five levels of muscarinic receptor status. Using a dynamic causal model - embodying a small network of coupled cortical microcircuits - we estimated synaptic parameters and their change across pharmacological conditions. The ensuing parameter estimates associated with (the neuromodulation of) synaptic efficacy showed both graded muscarinic effects and predictive validity between agonistic and antagonistic pharmacological conditions.This finding illustrates the potential utility of generative models of electrophysiological data as computational assays of muscarinic function. In application to EEG data of patients from heterogeneous spectrum diseases, e.g. schizophrenia, such models might help identify subgroups of patients that respond differentially to cholinergic treatments. Significance StatementIn psychiatry, the vast majority of pharmacological treatments affect actions of neuromodulatory transmitters, e.g. dopamine or acetylcholine. As treatment is largely trial-and-error based, one of the goals for computational psychiatry is to construct mathematical models that can serve as “computational assays” and infer the status of specific neuromodulatory systems in individual patients. This translational neuromodeling strategy has great promise for electrophysiological data in particular but requires careful validation. The present study demonstrates that the functional status of cholinergic (muscarinic) receptors can be inferred from electrophysiological data using dynamic causal models of neural circuits. While accuracy needs to be enhanced and our results must be replicated in larger samples, our current results provide proof-of-concept for computational assays of muscarinic function using EEG.

Unraveling the mechanisms of surround suppression in early visual processing.

This paper uses mathematical modeling to study the mechanisms of surround suppression in the primate visual cortex. We present a large-scale neural circuit model consisting of three interconnected components: LGN and two input layers (Layer 4Ca and Layer 6) of the primary visual cortex V1, covering several hundred hypercolumns. Anatomical structures are incorporated and physiological parameters from realistic modeling work are used. The remaining parameters are chosen to produce model outputs that emulate experimentally observed size-tuning curves. Our two main results are: (i) we discovered the character of the long-range connections in Layer 6 responsible for surround effects in the input layers; and (ii) we showed that a net-inhibitory feedback, i.e., feedback that excites I-cells more than E-cells, from Layer 6 to Layer 4 is conducive to producing surround properties consistent with experimental data. These results are obtained through parameter selection and model analysis. The effects of nonlinear recurrent excitation and inhibition are also discussed. A feature that distinguishes our model from previous modeling work on surround suppression is that we have tried to reproduce realistic lengthscales that are crucial for quantitative comparison with data. Due to its size and the large number of unknown parameters, the model is computationally challenging. We demonstrate a strategy that involves first locating baseline values for relevant parameters using a linear model, followed by the introduction of nonlinearities where needed. We find such a methodology effective, and propose it as a possibility in the modeling of complex biological systems.

A Hypothesis for Theta Rhythm Frequency Control in CA1 Microcircuits.

Computational models of neural circuits with varying levels of biophysical detail have been generated in pursuit of an underlying mechanism explaining the ubiquitous hippocampal theta rhythm. However, within the theta rhythm are at least two types with distinct frequencies associated with different behavioral states, an aspect that must be considered in pursuit of these mechanistic explanations. Here, using our previously developed excitatory-inhibitory network models that generate theta rhythms, we investigate the robustness of theta generation to intrinsic neuronal variability by building a database of heterogeneous excitatory cells and implementing them in our microcircuit model. We specifically investigate the impact of three key “building block” features of the excitatory cell model that underlie our model design: these cells' rheobase, their capacity for post-inhibitory rebound, and their spike-frequency adaptation. We show that theta rhythms at various frequencies can arise dependent upon the combination of these building block features, and we find that the speed of these oscillations are dependent upon the excitatory cells' response to inhibitory drive, as encapsulated by their phase response curves. Taken together, these findings support a hypothesis for theta frequency control that includes two aspects: (i) an internal mechanism that stems from the building block features of excitatory cell dynamics; (ii) an external mechanism that we describe as “inhibition-based tuning” of excitatory cell firing. We propose that these mechanisms control theta rhythm frequencies and underlie their robustness.