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Register a new userStatistical data assimilation for estimating electrophysiology simultaneously with connectivity within a biological neuronal network
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Eve Armstrong
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A method of data assimilation (DA) is employed to estimate electrophysiological parameters of neurons simultaneously with their synaptic connectivity in a small model biological network. The DA procedure is cast as an optimization, with a cost function consisting of both a measurement error and a model error term. An iterative reweighting of these terms permits a systematic method to identify the lowest minimum, within a local region of state space, on the surface of a non-convex cost function. In the model, two sets of parameter values are associated with two particular functional modes of network activity: simultaneous firing of all neurons, and a pattern-generating mode wherein the neurons burst in sequence. The DA procedure is able to recover these modes if: i) the stimulating electrical currents have chaotic waveforms, and ii) the measurements consist of the membrane voltages of all neurons in the circuit. Further, this method is able to prune a model of unnecessarily high dimensionality to a representation that contains the maximum dimensionality required to reproduce the provided measurements. This paper offers a proof-of-concept that DA has the potential to inform laboratory designs for estimating properties in small and isolatable functional circuits.
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A systematic assessment of global neural network connectivity through direct electrophysiological assays has remained technically unfeasible even in dissociated neuronal cultures. We introduce an improved algorithmic approach based on Transfer Entropy to reconstruct approximations to network structural connectivities from network activity monitored through calcium fluorescence imaging. Based on information theory, our method requires no prior assumptions on the statistics of neuronal firing and neuronal connections. The performance of our algorithm is benchmarked on surrogate time-series of calcium fluorescence generated by the simulated dynamics of a network with known ground-truth topology. We find that the effective network topology revealed by Transfer Entropy depends qualitatively on the time-dependent dynamic state of the network (e.g., bursting or non-bursting). We thus demonstrate how conditioning with respect to the global mean activity improves the performance of our method. [...] Compared to other reconstruction strategies such as cross-correlation or Granger Causality methods, our method based on improved Transfer Entropy is remarkably more accurate. In particular, it provides a good reconstruction of the network clustering coefficient, allowing to discriminate between weakly or strongly clustered topologies, whereas on the other hand an approach based on cross-correlations would invariantly detect artificially high levels of clustering. Finally, we present the applicability of our method to real recordings of in vitro cortical cultures. We demonstrate that these networks are characterized by an elevated level of clustering compared to a random graph (although not extreme) and by a markedly non-local connectivity.
Functional brain network has been widely studied to understand the relationship between brain organization and behavior. In this paper, we aim to explore the functional connectivity of brain network under a emph{multi-step} cognitive task involving with consecutive behaviors, and further understand the effect of behaviors on the brain organization. The functional brain networks are constructed base on a high spatial and temporal resolution fMRI dataset and analyzed via complex network based approach. We find that at voxel level the functional brain network shows robust small-worldness and scale-free characteristics, while its assortativity and rich-club organization are slightly restricted to order of behaviors performed. More interestingly, the functional connectivity of brain network in activated ROIs strongly correlates with behaviors and behaves obvious differences restricted to order of behaviors performed. These empirical results suggest that the brain organization has the generic properties of small-worldness and scale-free characteristics, and its diverse function connectivity emerging from activated ROIs is strongly driven by these behavioral activities via the plasticity of brain.
Our mysterious brain is believed to operate near a non-equilibrium point and generate critical self-organized avalanches in neuronal activity. Recent experimental evidence has revealed significant heterogeneity in both synaptic input and output connectivity, but whether the structural heterogeneity participates in the regulation of neuronal avalanches remains poorly understood. By computational modelling, we predict that different types of structural heterogeneity contribute distinct effects on avalanche neurodynamics. In particular, neuronal avalanches can be triggered at an intermediate level of input heterogeneity, but heterogeneous output connectivity cannot evoke avalanche dynamics. In the criticality region, the co-emergence of multi-scale cortical activities is observed, and both the avalanche dynamics and neuronal oscillations are modulated by the input heterogeneity. Remarkably, we show similar results can be reproduced in networks with various types of in- and out-degree distributions. Overall, these findings not only provide details on the underlying circuitry mechanisms of nonrandom synaptic connectivity in the regulation of neuronal avalanches, but also inspire testable hypotheses for future experimental studies.
Fluorescent nanodiamonds (FND) are carbon-based nanomaterials that can efficiently incorporate optically active photoluminescent centers such as the nitrogen-vacancy complex, thus making them promising candidates as optical biolabels and drug-delivery agents. FNDs exhibit bright fluorescence without photobleaching combined with high uptake rate and low cytotoxicity. Focusing on FNDs interference with neuronal function, here we examined their effect on cultured hippocampal neurons, monitoring the whole network development as well as the electrophysiological properties of single neurons. We observed that FNDs drastically decreased the frequency of inhibitory (from 1.81 Hz to 0.86 Hz) and excitatory (from 1.61 Hz to 0.68 Hz) miniature postsynaptic currents, and consistently reduced action potential (AP) firing frequency (by 36%), as measured by microelectrode arrays. On the contrary, bursts synchronization was preserved, as well as the amplitude of spontaneous inhibitory and excitatory events. Current-clamp recordings revealed that the ratio of neurons responding with AP trains of high-frequency (fast-spiking) versus neurons responding with trains of low-frequency (slow-spiking) was unaltered, suggesting that FNDs exerted a comparable action on neuronal subpopulations. At the single cell level, rapid onset of the somatic AP (kink) was drastically reduced in FND-treated neurons, suggesting a reduced contribution of axonal and dendritic components while preserving neuronal excitability.
Understanding the functioning of a neural system in terms of its underlying circuitry is an important problem in neuroscience. Recent developments in electrophysiology and imaging allow one to simultaneously record activities of hundreds of neurons. Inferring the underlying neuronal connectivity patterns from such multi-neuronal spike train data streams is a challenging statistical and computational problem. This task involves finding significant temporal patterns from vast amounts of symbolic time series data. In this paper we show that the frequent episode mining methods from the field of temporal data mining can be very useful in this context. In the frequent episode discovery framework, the data is viewed as a sequence of events, each of which is characterized by an event type and its time of occurrence and episodes are certain types of temporal patterns in such data. Here we show that, using the set of discovered frequent episodes from multi-neuronal data, one can infer different types of connectivity patterns in the neural system that generated it. For this purpose, we introduce the notion of mining for frequent episodes under certain temporal constraints; the structure of these temporal constraints is motivated by the application. We present algorithms for discovering serial and parallel episodes under these temporal constraints. Through extensive simulation studies we demonstrate that these methods are useful for unearthing patterns of neuronal network connectivity.
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