Investigation of the functioning of a neurohybrid system based on the FitzHugh–Nagumo radio generator and mouse hippocampal neurons
- Authors: Matveeva M.V.1, Fedulina A.A.1, Beltyukova A.V.1, Maltseva K.E.1, Gerasimova S.A.1, Mishchenko M.A.1, Mikhaylov A.N.1, Kazantsev V.B.1, Lebedeva A.V.1
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Affiliations:
- National Research Lobachevsky State University of Nizhny Novgorod
- Issue: Vol 18, No 4 (2023)
- Pages: 818-820
- Section: Conference proceedings
- URL: https://genescells.ru/2313-1829/article/view/623424
- DOI: https://doi.org/10.17816/gc623424
- ID: 623424
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Abstract
Currently, in the treatment of neurodegenerative diseases that are difficult to respond to drug therapy, electrical stimulation of the brain is performed through invasive intervention in damaged structures of the nervous tissue. The development and development of invasive technologies of closed-loop neural interfaces have made it possible to achieve great success in restoring neural connections, since they have finer and more precise stimulation settings that respond to changes in the physiological state, which is important in the process of restoring the functions of the nervous tissue. Advances in these areas open up prospects for the treatment of a wide range of diseases of the motor system and neurodegenerative diseases of the brain.
In this study, a neurohybrid closed system was used, consisting of a FitzHugh-Nagumo radio generator and live surviving slices of the mouse brain hippocampus. For the preparation of surviving slices of the hippocampus, sexually mature males aged 2-3 months of the C57BL/6 mouse line were used. For the preparation and incubation of slices of the hippocampus, a solution of artificial cerebrospinal fluid (ACSF) was used, composition in (mM): 126 NaCl; 3.5 KCl; 1.2 KH2PO4; 26 NaHCO3; 1.3 MgCl * 6H2O; 2 CaCl2 * 6H2O; 10 D-glucose at constant carbogen saturation (95% O2 and 5% CO2). Registration of the electrical activity of brain neurons was carried out using optical and electrophysiological methods.
In experiments on pairing a neuron-like FitzHugh-Nagumo generator and biological nerve cells in a closed circuit, an effect was obtained when the activity of brain nerve cells switched the generator to a self-oscillating mode. The evoked oscillations in the neuron-like generator provided an effective stimulus for the activation of nerve fibers in the perforant pathway of the hippocampus. As a result, it was possible to fix a decrease in the frequency of the generator impulses, which was provoked by the responses of living neurons to the incoming stimulus from the neuron-like generator. These results show the ability of live neural networks to control an artificial signal by adjusting its parameters by changing their own activity and confirm the efficiency of using closed loop systems when combining live and artificial neurons. The present study requires further experiments to create more physiological conditions for the functioning of the proposed neurohybrid system. In addition, this neurohybrid system will be improved and have adaptive properties through the use of memristive devices. Advances in this direction will help solve the urgent problem of restoring lost brain functions at the cellular and network levels.
Full Text
Currently, for the treatment of neurodegenerative diseases that are unresponsive to drug therapy, invasive electrical stimulation of damaged neural tissue structures is employed. The advancement of invasive technologies in closed-loop neural interfaces has facilitated the restoration of neural connections. These technologies boast finer and more precise stimulation settings that effectively respond to changes in physiological states, imperative for the process of restoring nervous tissue function. Advancements in these domains create opportunities for treating various motor system disorders and neurodegenerative brain diseases.
In this study, we used a neurohybrid closed system that comprised a FitzHugh–Nagumo radio generator and viable slices of the mouse brain hippocampus. For the acquisition of these viable hippocampal slices, we used sexually mature male mice of the C57BL/6 mouse strain at the age of 2–3 months. An artificial cerebrospinal fluid (ACSF) solution was used to prepare and incubate hippocampal slices, consisting of the following in millimolar (mM): 126 NaCl, 3.5 KCl, 1.2 KH2PO4, 26 NaHCO3, 1.3 MgCl*6H2O, 2 CaCl2*6H2O, and 10 D-glucose, while maintaining 95% O2 and 5% CO2 carbogen saturation. The electrical activity of brain neurons was recorded using both optical and electrophysiological methods.
In experiments that paired a neuron-like FitzHugh–Nagumo generator with biological nerve cells in a closed circuit, an effect occurred when the activity of brain nerve cells caused the generator to switch to a self-oscillating mode. The induced oscillations in the neuron-like generator acted as an effective stimulus for the activation of nerve fibers in the perforant pathway of the hippocampus. The frequency of generator impulses decreased due to the response of living neurons to the incoming stimulus from the neuron-like generator. However, this decrease was rectified. This study demonstrates the capability of live neural networks to manipulate an artificial signal by modifying its parameters through adjustments to their own activity. This confirms the efficacy of implementing closed-loop systems that integrate both living and artificial neurons. Future experiments should focus on creating more physiological conditions to enhance the performance of the proposed neurohybrid system. Additionally, the neurohybrid system will be enhanced and possess adaptable features with the incorporation of memristive devices. Advances in this direction will help solve the urgent problem of restoring lost brain functions at the cellular and network levels.
ADDITIONAL INFORMATION
Authors’ contribution. All authors made a substantial contribution to the conception of the work, acquisition, analysis, interpretation of data for the work, drafting and revising the work, final approval of the version to be published and agree to be accountable for all aspects of the work.
Funding sources. The research was conducted within the framework of the scientific program of the National Center of Physics and Mathematics “Research and Development of Neuromorphic and Neurohybrid Systems of Artificial Intelligence” (Contract No. 96-2022/181 dated July 13, 2022) within the scientific program of the National Center of Physics and Mathematics (direction “Artificial Intelligence and Big Data in Technical, Industrial, Natural and Social Systems”).
Competing interests. The authors declare that they have no competing interests.
About the authors
M. V. Matveeva
National Research Lobachevsky State University of Nizhny Novgorod
Author for correspondence.
Email: m.matveeva288@gmail.com
Russian Federation, Nizhny Novgorod
A. A. Fedulina
National Research Lobachevsky State University of Nizhny Novgorod
Email: m.matveeva288@gmail.com
Russian Federation, Nizhny Novgorod
A. V. Beltyukova
National Research Lobachevsky State University of Nizhny Novgorod
Email: m.matveeva288@gmail.com
Russian Federation, Nizhny Novgorod
K. E. Maltseva
National Research Lobachevsky State University of Nizhny Novgorod
Email: m.matveeva288@gmail.com
Russian Federation, Nizhny Novgorod
S. A. Gerasimova
National Research Lobachevsky State University of Nizhny Novgorod
Email: m.matveeva288@gmail.com
Russian Federation, Nizhny Novgorod
M. A. Mishchenko
National Research Lobachevsky State University of Nizhny Novgorod
Email: m.matveeva288@gmail.com
Russian Federation, Nizhny Novgorod
A. N. Mikhaylov
National Research Lobachevsky State University of Nizhny Novgorod
Email: m.matveeva288@gmail.com
Russian Federation, Nizhny Novgorod
V. B. Kazantsev
National Research Lobachevsky State University of Nizhny Novgorod
Email: m.matveeva288@gmail.com
Russian Federation, Nizhny Novgorod
A. V. Lebedeva
National Research Lobachevsky State University of Nizhny Novgorod
Email: m.matveeva288@gmail.com
Russian Federation, Nizhny Novgorod
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