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Causal relationship of CA3 back-projection to the dentate gyrus and its role in CA1 fast ripple generation

BACKGROUND: Pathophysiological evidence from temporal lobe epilepsy models highlights the hippocampus as the most affected structure due to its high degree of neuroplasticity and control of the dynamics of limbic structures, which are necessary to encode information, conferring to it an intrinsic ep...

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Autores principales: Núñez-Ochoa, Miguel A., Chiprés-Tinajero, Gustavo A., González-Domínguez, Nadia P., Medina-Ceja, Laura
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130286/
https://www.ncbi.nlm.nih.gov/pubmed/34001031
http://dx.doi.org/10.1186/s12868-021-00641-4
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author Núñez-Ochoa, Miguel A.
Chiprés-Tinajero, Gustavo A.
González-Domínguez, Nadia P.
Medina-Ceja, Laura
author_facet Núñez-Ochoa, Miguel A.
Chiprés-Tinajero, Gustavo A.
González-Domínguez, Nadia P.
Medina-Ceja, Laura
author_sort Núñez-Ochoa, Miguel A.
collection PubMed
description BACKGROUND: Pathophysiological evidence from temporal lobe epilepsy models highlights the hippocampus as the most affected structure due to its high degree of neuroplasticity and control of the dynamics of limbic structures, which are necessary to encode information, conferring to it an intrinsic epileptogenicity. A loss in this control results in observable oscillatory perturbations called fast ripples, in epileptic rats those events are found in CA1, CA3, and the dentate gyrus (DG), which are the principal regions of the trisynaptic circuit of the hippocampus. The present work used Granger causality to address which relationships among these three regions of the trisynaptic circuit are needed to cause fast ripples in CA1 in an in vivo model. For these purposes, male Wistar rats (210–300 g) were injected with a single dose of pilocarpine hydrochloride (2.4 mg/2 µl) into the right lateral ventricle and video-monitored 24 h/day to detect spontaneous and recurrent seizures. Once detected, rats were implanted with microelectrodes in these regions (fixed-recording tungsten wire electrodes, 60-μm outer diameter) ipsilateral to the pilocarpine injection. A total of 336 fast ripples were recorded and probabilistically characterized, from those fast ripples we made a subset of all the fast ripple events associated with sharp-waves in CA1 region (n = 40) to analyze them with Granger Causality. RESULTS: Our results support existing evidence in vitro in which fast ripple events in CA1 are initiated by CA3 multiunit activity and describe a general synchronization in the theta band across the three regions analyzed DG, CA3, and CA1, just before the fast ripple event in CA1 have begun. CONCLUSION: This in vivo study highlights the causal participation of the CA3 back-projection to the DG, a connection commonly overlooked in the trisynaptic circuit, as a facilitator of a closed-loop among these regions that prolongs the excitatory activity of CA3. We speculate that the loss of inhibitory drive of DG and the mechanisms of ripple-related memory consolidation in which also the CA3 back-projection to DG has a fundamental role might be underlying processes of the fast ripples generation in CA1. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12868-021-00641-4.
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spelling pubmed-81302862021-05-18 Causal relationship of CA3 back-projection to the dentate gyrus and its role in CA1 fast ripple generation Núñez-Ochoa, Miguel A. Chiprés-Tinajero, Gustavo A. González-Domínguez, Nadia P. Medina-Ceja, Laura BMC Neurosci Research Article BACKGROUND: Pathophysiological evidence from temporal lobe epilepsy models highlights the hippocampus as the most affected structure due to its high degree of neuroplasticity and control of the dynamics of limbic structures, which are necessary to encode information, conferring to it an intrinsic epileptogenicity. A loss in this control results in observable oscillatory perturbations called fast ripples, in epileptic rats those events are found in CA1, CA3, and the dentate gyrus (DG), which are the principal regions of the trisynaptic circuit of the hippocampus. The present work used Granger causality to address which relationships among these three regions of the trisynaptic circuit are needed to cause fast ripples in CA1 in an in vivo model. For these purposes, male Wistar rats (210–300 g) were injected with a single dose of pilocarpine hydrochloride (2.4 mg/2 µl) into the right lateral ventricle and video-monitored 24 h/day to detect spontaneous and recurrent seizures. Once detected, rats were implanted with microelectrodes in these regions (fixed-recording tungsten wire electrodes, 60-μm outer diameter) ipsilateral to the pilocarpine injection. A total of 336 fast ripples were recorded and probabilistically characterized, from those fast ripples we made a subset of all the fast ripple events associated with sharp-waves in CA1 region (n = 40) to analyze them with Granger Causality. RESULTS: Our results support existing evidence in vitro in which fast ripple events in CA1 are initiated by CA3 multiunit activity and describe a general synchronization in the theta band across the three regions analyzed DG, CA3, and CA1, just before the fast ripple event in CA1 have begun. CONCLUSION: This in vivo study highlights the causal participation of the CA3 back-projection to the DG, a connection commonly overlooked in the trisynaptic circuit, as a facilitator of a closed-loop among these regions that prolongs the excitatory activity of CA3. We speculate that the loss of inhibitory drive of DG and the mechanisms of ripple-related memory consolidation in which also the CA3 back-projection to DG has a fundamental role might be underlying processes of the fast ripples generation in CA1. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12868-021-00641-4. BioMed Central 2021-05-17 /pmc/articles/PMC8130286/ /pubmed/34001031 http://dx.doi.org/10.1186/s12868-021-00641-4 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Núñez-Ochoa, Miguel A.
Chiprés-Tinajero, Gustavo A.
González-Domínguez, Nadia P.
Medina-Ceja, Laura
Causal relationship of CA3 back-projection to the dentate gyrus and its role in CA1 fast ripple generation
title Causal relationship of CA3 back-projection to the dentate gyrus and its role in CA1 fast ripple generation
title_full Causal relationship of CA3 back-projection to the dentate gyrus and its role in CA1 fast ripple generation
title_fullStr Causal relationship of CA3 back-projection to the dentate gyrus and its role in CA1 fast ripple generation
title_full_unstemmed Causal relationship of CA3 back-projection to the dentate gyrus and its role in CA1 fast ripple generation
title_short Causal relationship of CA3 back-projection to the dentate gyrus and its role in CA1 fast ripple generation
title_sort causal relationship of ca3 back-projection to the dentate gyrus and its role in ca1 fast ripple generation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130286/
https://www.ncbi.nlm.nih.gov/pubmed/34001031
http://dx.doi.org/10.1186/s12868-021-00641-4
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