The architecture of neuron connectivity in brain networks is one of the basic mechanisms by which to organize and sustain a particular function of the brain circuitry. There are areas of the brain composed of well-organized layers of neurons connected by unidirectional synaptic connections (e.g., cortex, hippocampus). Re-engineering of the neural circuits with such a heterogeneous network structure in culture may uncover basic mechanisms of emergent information functions of these circuits. In this study, we present such a model designed with two subpopulations of primary hippocampal neurons (E18) with directed connectivity grown in a microfluidic device with asymmetric channels. We analysed and compared neurite growth in the microchannels with various shapes that promoted growth dominantly in one direction. We found an optimal geometric shape features of the microchannels in which the axons coupled two chambers with the neurons. The axons grew in the promoted direction and formed predefined connections during the first 6 days in vitro (DIV). The microfluidic devices were coupled with microelectrode arrays (MEAs) to confirm unidirectional spiking pattern propagation through the microchannels between two compartments. We found that, during culture development, the defined morphological and functional connectivity formed and was maintained for up to 25 DIV.
Dense dissociated hippocampal cultures are known to generate spontaneous bursting electrical activity which can be recorded by multielectrode arrays. We have analyzed spatio-temporal profiles of the distribution of spikes in the bursts recorded after 2 weeks in vitro. We have found a statistically significant similarity between the spiking patterns in sequential bursting events, we refer to these spiking patterns as spiking signatures. Such spiking signatures may appear in different parts of the bursts, including the activation patterns – the first spike times in the bursts, and deactivation patterns – the last spike times in the bursts. Moreover, these patterns may display apparent time scaling, e.g., they may be replayed in the subsequent bursts at different speeds, while preserving the spiking order. We discuss how such properties of the bursts may be associated with the formation of repeatable signaling pathways in cultured networks in vitro.
This article presents a rehabilitation technique based on a lower-limb exoskeleton integrated with a human-machine interface (HMI). HMI is used to record and process multimodal signals collected using a foot motor imagery (MI)-based brain-machine interface (BMI) and multichannel electromyographic (EMG) signals recorded from leg muscles. Current solutions of HMI-equipped rehabilitation assistive technologies tested under laboratory conditions demonstrated a great deal of success, but faced several difficulties caused by the limited accuracy of detecting MI electroencephalography (EEG) and the reliability of online control when executing a movement by patients dressed in an exoskeleton. In the case of lowerlimb representation, there is still the problem of reliably distinguishing leg movement intentions and differentiating them in BMI systems. Targeting the design of a rehabilitation technique replicating the natural mode of motor control in exoskeleton walking patients, we have shown how the combined use of multimodal signals can improve the accuracy, performance, and reliability of HMI. The system was tested on healthy subjects operating the exoskeleton under different conditions. The study also resulted in algorithms of multimodal HMI data collection, processing, and classification. The developed system can analyze up to 15 signals simultaneously in real-time during a movement. Foot MI is extracted from EEG signals (seven channels) using the event-related (de)synchronization effect. Supplemented by EMG signals reflecting motor intention, the control system can initiate and differentiate the movement of the right and left legs with a high degree of reliability. The classification and control system permits one to work online when the exoskeleton is executing a movement.
Here we provide a perspective concept of neurohybrid memristive chip based on the combination of living neural networks cultivated in microfluidic/microelectrode system, metal-oxide memristive devices or arrays integrated with mixed-signal CMOS layer to control the analog memristive circuits, process the decoded information, and arrange a feedback stimulation of biological culture as parts of a bidirectional neurointerface. Our main focus is on the state-of-the-art approaches for cultivation and spatial ordering of the network of dissociated hippocampal neuron cells, fabrication of a large-scale crossbar array of memristive devices tailored using device engineering, resistive state programming, or non-linear dynamics, as well as hardware implementation of spiking neural networks (SNNs) based on the arrays of memristive devices and integrated CMOS electronics. The concept represents an example of a brain-on-chip system belonging to a more general class of memristive neurohybrid systems for a newgeneration robotics, artificial intelligence, and personalized medicine, discussed in the framework of the proposed roadmap for the next decade period.
The functional role of astrocyte calcium signaling in brain information processing was intensely debated in recent decades. This interest was motivated by high resolution imaging techniques showing highly developed structure of distal astrocyte processes. Another point was the evidence of bi-directional astrocytic regulation of neuronal activity. To analyze the effects of interplay of calcium signals in processes and in soma mediating correlations between local signals and the cell-level response of the astrocyte we proposed spatially extended model of the astrocyte calcium dynamics. Specifically, we investigated how spatiotemporal properties of Ca 2+ dynamics in spatially extended astrocyte model can coordinate (e.g., synchronize) networks of neurons and synapses.
The olivo-cerebellar network is a key neuronal circuit that provides high-level motor control in the vertebrate CNS. Functionally, its network dynamics is organized around the oscillatory membrane potential properties of inferior olive (IO) neurons and their electrotonic connectivity. Because IO action potentials are generated at the peaks of the quasisinusoidal membrane potential oscillations, their temporal firing properties are defined by the IO rhythmicity. Excitatory inputs to these neurons can produce oscillatory phase shifts without modifying the amplitude or frequency of the oscillations, allowing well defined time-shift modulation of action potential generation. Moreover, the resulting phase is defined only by the amplitude and duration of the reset stimulus and is independent of the original oscillatory phase when the stimulus was delivered. This reset property, henceforth referred to as selfreferential phase reset, results in the generation of organized clusters of electrically coupled cells that oscillate in phase and are controlled by inhibitory feedback loops through the cerebellar nuclei and the cerebellar cortex. These clusters provide a dynamical representation of arbitrary motor intention patterns that are further mapped to the motor execution system. Being supplied with sensory inputs, the olivo-cerebellar network is capable of rearranging the clusters during the process of movement execution. Accordingly, the phase of the IO oscillators can be rapidly reset to a desired phase independently of the history of phase evolution. The goal of this article is to show how this selfreferential phase reset may be implemented into a motor control system by using a biologically based mathematical model. neuron ͉ nonlinear ͉ oscillation ͉ Andronov-Hopf bifurcation C oordinated motor control signals addressing large numbers of muscles at a given time must implement strict temporal coherence, also known as ''temporal motor binding,'' to generate appropriate motricity (1). Electrophysiological studies have indicated that such motor intention patterns require proper olivocerebellar system function (1-4). And, in particular, sets of time-coherent inferior olive (IO) action potentials reach given motor neuron pools by means of the cerebellar nuclei (1, 5-7). To provide the required synchrony of muscle activation, the IO signals must be temporally coherent at the final motor path regardless of the distance between the activated muscle groups. As such, then, the main coherence control parameter is the mutual temporal shifts among sequences of action potentials innervating different muscles. Recent experimental work indicates that such a temporal signal mechanism is provided by the sequence of oscillatory events in the olivo-cerebellar system (7). The possibility that a ''universal control system,'' based on olivo-cerebellar physiology, may be implemented in analog hardware electronic chips has been proposed (8).Indeed, temporal motor intention patterns may be formed as oscillatory phase clusters in the IO (9-12). ...
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