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An inter-regional cortical tract is one of the most fundamental architectural motifs that integrates neural circuits to orchestrate and generate complex functions of the human brain. To understand the mechanistic significance of inter-regional projections on development of neural circuits, we investigated an in vitro neural tissue model for inter-regional connections, in which two cerebral organoids are connected with a bundle of reciprocally extended axons. The connected organoids produced more complex and intense oscillatory activity than conventional or directly fused cerebral organoids, suggesting the inter-organoid axonal connections enhance and support the complex network activity. In addition, optogenetic stimulation of the inter-organoid axon bundles could entrain the activity of the organoids and induce robust short-term plasticity of the macroscopic circuit. These results demonstrated that the projection axons could serve as a structural hub that boosts functionality of the organoid-circuits. This model could contribute to further investigation on development and functions of macroscopic neuronal circuits in vitro., (© 2024. The Author(s).)

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., (© 2022. The Author(s).)

Restoration of the communication between brain circuitry is a crucial step in the recovery of brain damage induced by traumatic injuries or neurological insults. In this work we present a study of real-time unidirectional communication between a spiking neuronal network (SNN) implemented on digital platform and an in-vitro biological neuronal network (BNN), generating similar spontaneous patterns of activity both spatial and temporal. The communication between the networks was established using patterned optogenetic stimulation via a modified digital light projector (DLP) receiving real-time input dictated by the spiking neurons' state. Each stimulation consisted of a binary image composed of 8 × 8 squares, representing the state of 64 excitatory neurons. The spontaneous and evoked activity of the biological neuronal network was recorded using a multi-electrode array in conjunction with calcium imaging. The image was projected in a sub-portion of the cultured network covered by a subset of the all electrodes. The unidirectional information transmission (SNN to BNN) is estimated using the similarity matrix of the input stimuli and output firing. Information transmission was studied in relation to the distribution of stimulus frequency and stimulus intensity, both regulated by the spontaneous dynamics of the SNN, and to the entrainment of the biological networks. We demonstrate that high information transfer from SNN to BNN is possible and identify a set of conditions under which such transfer can occur, namely when the spiking network synchronizations drive the biological synchronizations (entrainment) and in a linear regime response to the stimuli. This research provides further evidence of possible application of miniaturized SNN in future neuro-prosthetic devices for local replacement of injured micro-circuitries capable to communicate within larger brain networks.

One of the main limitations preventing the realization of a successful dialogue between the brain and a putative enabling device is the intricacy of brain signals. In this perspective, closed-loop in vitro systems can be used to investigate the interactions between a network of neurons and an external system, such as an interacting environment or an artificial device. In this chapter, we provide an overview of closed-loop in vitro systems, which have been developed for investigating potential neuroprosthetic applications. In particular, we first explore how to modify or set a target dynamical behavior in a network of neurons. We then analyze the behavior of in vitro systems connected to artificial devices, such as robots. Finally, we provide an overview of biological neuronal networks interacting with artificial neuronal networks, a configuration currently offering a promising solution for clinical applications.

Neurological diseases can be studied by performing bio-hybrid experiments using a real-time biomimetic Spiking Neural Network (SNN) platform. The Hodgkin-Huxley model offers a set of equations including biophysical parameters which can serve as a base to represent different classes of neurons and affected cells. Also, connecting the artificial neurons to the biological cells would allow us to understand the effect of the SNN stimulation using different parameters on nerve cells. Thus, designing a real-time SNN could useful for the study of simulations of some part of the brain. Here, we present a different approach to optimize the Hodgkin-Huxley equations adapted for Field Programmable Gate Array (FPGA) implementation. The equations of the conductance have been unified to allow the use of same functions with different parameters for all ionic channels. The low resources and high-speed implementation also include features, such as synaptic noise using the Ornstein–Uhlenbeck process and different synapse receptors including AMPA, GABAa, GABAb, and NMDA receptors. The platform allows real-time modification of the neuron parameters and can output different cortical neuron families like Fast Spiking (FS), Regular Spiking (RS), Intrinsically Bursting (IB), and Low Threshold Spiking (LTS) neurons using a Digital to Analog Converter (DAC). Gaussian distribution of the synaptic noise highlights similarities with the biological noise. Also, cross-correlation between the implementation and the model shows strong correlations, and bifurcation analysis reproduces similar behavior compared to the original Hodgkin-Huxley model. The implementation of one core of calculation uses 3% of resources of the FPGA and computes in real-time 500 neurons with 25,000 synapses and synaptic noise which can be scaled up to 15,000 using all resources. This is the first step toward neuromorphic system which can be used for the simulation of bio-hybridization and for the study of neurological disorders or the advanced research on neuroprosthesis to regain lost function. [ABSTRACT FROM AUTHOR]

Reuse methodologies are now widely used to design digital circuits. They are based on the concept of intellectual property (IP), or virtual block of computing, characterized by a behavioral model, synthesizable or not. The design reuse for analog integrated systems is much less natural and less standardized. This paper addresses the issue of an analog design flow based on reuse, focusing on three key issues: the formal content of the IP block, the design of a reusable analog IP, and the organization of a design flow centered on an IP library. After a conceptual overview, this paper presents the methodological principles and details examples with a tutorial intention. The objective is to guide the designer involved in the process of developing analog IPs and corresponding design flow. This method is inspired by platform-based design and adapted here on an original case study: the design of full-custom neuromimetic integrated circuits, built from specific analog computational blocks. The development of reusable IPs represents an additional effort, mainly for behavioral modeling and characterization. Nevertheless, the steps illustrated in this case study show that the extra time provides a definite advantage to future design projects. [ABSTRACT FROM AUTHOR]