Investigation of hippocampal synaptic plasticity in a mutant mice line predisposed to epileptiform activity
- Authors: Fedulina A.A.1, Matveeva M.V.1, Maltseva K.E.1, Lebedeva A.V.1, Tarabykin V.S.2
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Affiliations:
- Institute of Neurosciences, National Research Lobachevsky State University of Nizhny Novgorod
- Institute of Cell Biology and Neurobiology, Charité-Universitätsmedizin Berlin
- Issue: Vol 18, No 4 (2023)
- Pages: 462-464
- Section: Conference proceedings
- URL: https://genescells.ru/2313-1829/article/view/623290
- DOI: https://doi.org/10.17816/gc623290
- ID: 623290
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Abstract
The human genetic code is nearly decoded and genetic mutations garnered significant attention from researchers. Investigating mutations that cause disease manifestation and determine genetic predisposition is a priority in this field. The investigation of novel disease manifestation mechanisms represents a contemporary and original strategy that advances the development of treatment and correction methods for multiple neurodegenerative conditions in humans. Epilepsy constitutes one of the prevalent forms of neurological disorders. A full understanding of the complex mechanisms that drive epileptogenesis and seizure onset in temporal lobe and other forms of epilepsy cannot be fully achieved through human clinical trials. Consequently, the use of relevant animal models becomes indispensable.
The aim of this study is to investigate the synaptic transmission and long-term plasticity of the hippocampus in a mutant strain of mice known as S5-1 that exhibits epileptiform activity. The study focuses on S5-1 strain mice that have the tendency to develop epileptiform activity after the induction of ENU-mutagenesis in the DNA molecule. To investigate in vitro activity, researchers use a method that combines electrophysiological and optical techniques to register local field potentials on surviving brain slices.
To evaluate long-term synaptic plasticity, two iterations of the protocol were used: one involved applying small stimulation amplitudes (50 mA), while the other called for large amplitudes (500 mA). In the former case, a high frequency of long-term potentiation was observed within the group with epileptiform activity. In animals with the phenotype, potentiation was between 150–170% of the average response rate to theta-burst stimulation, whereas values in the control group only reached 120–125%. The findings indicate that in a cohort of animals with an epileptiform phenotype, nerve fibers are hyperactivated, which is one of the mechanisms contributing to epileptogenesis. Moreover, in the second scenario, by employing high stimulation amplitudes, a marked decline in synaptic transmission was identified in animals with epileptiform behavioral activity (120–150%) as opposed to the control group (200–250%). A significant reduction in long-term synaptic plasticity in animals displaying epileptiform activity when compared to the control group under high stress stimulation amplitudes may suggest a disruption of synaptic transmission at the molecular and cellular levels, potentially resulting in memory impairment or a decline in cognitive abilities among mutant animals exhibiting epilepsy symptoms.
A plausible mechanism for altering synaptic transmission in the hippocampus of the S5-1 mutant line of mice is that point mutations occur after exposure to mutagen which leads to the development of various pathologies. One of these pathologies results in a disruption of the cytoarchitecture of the cerebral cortex. Consequently, subcortical structures, especially the hippocampus, are indirectly affected leading to the onset of audiogenic seizures. As a consequence, disruptions occur in synaptic transmission and plasticity, potentially resulting in memory impairment and other cognitive impairments. However, additional research is needed to examine the potential mechanism underlying the development of brain disorders in mutant animals.
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Full Text
The human genetic code is nearly decoded and genetic mutations garnered significant attention from researchers. Investigating mutations that cause disease manifestation and determine genetic predisposition is a priority in this field. The investigation of novel disease manifestation mechanisms represents a contemporary and original strategy that advances the development of treatment and correction methods for multiple neurodegenerative conditions in humans. Epilepsy constitutes one of the prevalent forms of neurological disorders. A full understanding of the complex mechanisms that drive epileptogenesis and seizure onset in temporal lobe and other forms of epilepsy cannot be fully achieved through human clinical trials. Consequently, the use of relevant animal models becomes indispensable.
The aim of this study is to investigate the synaptic transmission and long-term plasticity of the hippocampus in a mutant strain of mice known as S5-1 that exhibits epileptiform activity. The study focuses on S5-1 strain mice that have the tendency to develop epileptiform activity after the induction of ENU-mutagenesis in the DNA molecule. To investigate in vitro activity, researchers use a method that combines electrophysiological and optical techniques to register local field potentials on surviving brain slices.
To evaluate long-term synaptic plasticity, two iterations of the protocol were used: one involved applying small stimulation amplitudes (50 mA), while the other called for large amplitudes (500 mA). In the former case, a high frequency of long-term potentiation was observed within the group with epileptiform activity. In animals with the phenotype, potentiation was between 150–170% of the average response rate to theta-burst stimulation, whereas values in the control group only reached 120–125%. The findings indicate that in a cohort of animals with an epileptiform phenotype, nerve fibers are hyperactivated, which is one of the mechanisms contributing to epileptogenesis. Moreover, in the second scenario, by employing high stimulation amplitudes, a marked decline in synaptic transmission was identified in animals with epileptiform behavioral activity (120–150%) as opposed to the control group (200–250%). A significant reduction in long-term synaptic plasticity in animals displaying epileptiform activity when compared to the control group under high stress stimulation amplitudes may suggest a disruption of synaptic transmission at the molecular and cellular levels, potentially resulting in memory impairment or a decline in cognitive abilities among mutant animals exhibiting epilepsy symptoms.
A plausible mechanism for altering synaptic transmission in the hippocampus of the S5-1 mutant line of mice is that point mutations occur after exposure to mutagen which leads to the development of various pathologies. One of these pathologies results in a disruption of the cytoarchitecture of the cerebral cortex. Consequently, subcortical structures, especially the hippocampus, are indirectly affected leading to the onset of audiogenic seizures. As a consequence, disruptions occur in synaptic transmission and plasticity, potentially resulting in memory impairment and other cognitive impairments. However, additional research is needed to examine the potential mechanism underlying the development of brain disorders in mutant animals.
ADDITIONAL INFORMATION
Funding sources. The study was supported by the Russian Science Foundation grant No. 21-65-00017.
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, and final approval of the version to be published and agree to be accountable for all aspects of the work.
Competing interests. The authors declare that they have no competing interests.
About the authors
A. A. Fedulina
Institute of Neurosciences, National Research Lobachevsky State University of Nizhny Novgorod
Author for correspondence.
Email: fedulina@neuro.nnov.ru
Russian Federation, Nizhny Novgorod
M. V. Matveeva
Institute of Neurosciences, National Research Lobachevsky State University of Nizhny Novgorod
Email: fedulina@neuro.nnov.ru
Russian Federation, Nizhny Novgorod
K. E. Maltseva
Institute of Neurosciences, National Research Lobachevsky State University of Nizhny Novgorod
Email: fedulina@neuro.nnov.ru
Russian Federation, Nizhny Novgorod
A. V. Lebedeva
Institute of Neurosciences, National Research Lobachevsky State University of Nizhny Novgorod
Email: fedulina@neuro.nnov.ru
Russian Federation, Nizhny Novgorod
V. S. Tarabykin
Institute of Cell Biology and Neurobiology, Charité-Universitätsmedizin Berlin
Email: fedulina@neuro.nnov.ru
Germany, Berlin
References
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