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The Stop Signal Task for Measuring Behavioral Inhibition in Mice With Increased Sensitivity and High-Throughput Operation
Ceasing an ongoing motor response requires action cancelation. This is impaired in many pathologies such as attention deficit disorder and schizophrenia. Action cancelation is measured by the stop signal task that estimates how quickly a motor response can be stopped when it is already being execute...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8696275/ https://www.ncbi.nlm.nih.gov/pubmed/34955779 http://dx.doi.org/10.3389/fnbeh.2021.777767 |
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author | Caglayan, Alican Stumpenhorst, Katharina Winter, York |
author_facet | Caglayan, Alican Stumpenhorst, Katharina Winter, York |
author_sort | Caglayan, Alican |
collection | PubMed |
description | Ceasing an ongoing motor response requires action cancelation. This is impaired in many pathologies such as attention deficit disorder and schizophrenia. Action cancelation is measured by the stop signal task that estimates how quickly a motor response can be stopped when it is already being executed. Apart from human studies, the stop signal task has been used to investigate neurobiological mechanisms of action cancelation overwhelmingly in rats and only rarely in mice, despite the need for a genetic model approach. Contributing factors to the limited number of mice studies may be the long and laborious training that is necessary and the requirement for a very loud (100 dB) stop signal. We overcame these limitations by employing a fully automated home-cage-based setup. We connected a home-cage to the operant box via a gating mechanism, that allowed individual ID chipped mice to start sessions voluntarily. Furthermore, we added a negative reinforcement consisting of a mild air puff with escape option to the protocol. This specifically improved baseline inhibition to 94% (from 84% with the conventional approach). To measure baseline inhibition the stop is signaled immediately with trial onset thus measuring action restraint rather than action cancelation ability. A high baseline allowed us to measure action cancelation ability with higher sensitivity. Furthermore, our setup allowed us to reduce the intensity of the acoustic stop signal from 100 to 70 dB. We constructed inhibition curves from stop trials with daily adjusted delays to estimate stop signal reaction times (SSRTs). SSRTs (median 88 ms) were lower than reported previously, which we attribute to the observed high baseline inhibition. Our automated training protocol reduced training time by 17% while also promoting minimal experimenter involvement. This sensitive and labor efficient stop signal task procedure should therefore facilitate the investigation of action cancelation pathologies in genetic mouse models. |
format | Online Article Text |
id | pubmed-8696275 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-86962752021-12-24 The Stop Signal Task for Measuring Behavioral Inhibition in Mice With Increased Sensitivity and High-Throughput Operation Caglayan, Alican Stumpenhorst, Katharina Winter, York Front Behav Neurosci Behavioral Neuroscience Ceasing an ongoing motor response requires action cancelation. This is impaired in many pathologies such as attention deficit disorder and schizophrenia. Action cancelation is measured by the stop signal task that estimates how quickly a motor response can be stopped when it is already being executed. Apart from human studies, the stop signal task has been used to investigate neurobiological mechanisms of action cancelation overwhelmingly in rats and only rarely in mice, despite the need for a genetic model approach. Contributing factors to the limited number of mice studies may be the long and laborious training that is necessary and the requirement for a very loud (100 dB) stop signal. We overcame these limitations by employing a fully automated home-cage-based setup. We connected a home-cage to the operant box via a gating mechanism, that allowed individual ID chipped mice to start sessions voluntarily. Furthermore, we added a negative reinforcement consisting of a mild air puff with escape option to the protocol. This specifically improved baseline inhibition to 94% (from 84% with the conventional approach). To measure baseline inhibition the stop is signaled immediately with trial onset thus measuring action restraint rather than action cancelation ability. A high baseline allowed us to measure action cancelation ability with higher sensitivity. Furthermore, our setup allowed us to reduce the intensity of the acoustic stop signal from 100 to 70 dB. We constructed inhibition curves from stop trials with daily adjusted delays to estimate stop signal reaction times (SSRTs). SSRTs (median 88 ms) were lower than reported previously, which we attribute to the observed high baseline inhibition. Our automated training protocol reduced training time by 17% while also promoting minimal experimenter involvement. This sensitive and labor efficient stop signal task procedure should therefore facilitate the investigation of action cancelation pathologies in genetic mouse models. Frontiers Media S.A. 2021-12-09 /pmc/articles/PMC8696275/ /pubmed/34955779 http://dx.doi.org/10.3389/fnbeh.2021.777767 Text en Copyright © 2021 Caglayan, Stumpenhorst and Winter. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Behavioral Neuroscience Caglayan, Alican Stumpenhorst, Katharina Winter, York The Stop Signal Task for Measuring Behavioral Inhibition in Mice With Increased Sensitivity and High-Throughput Operation |
title | The Stop Signal Task for Measuring Behavioral Inhibition in Mice With Increased Sensitivity and High-Throughput Operation |
title_full | The Stop Signal Task for Measuring Behavioral Inhibition in Mice With Increased Sensitivity and High-Throughput Operation |
title_fullStr | The Stop Signal Task for Measuring Behavioral Inhibition in Mice With Increased Sensitivity and High-Throughput Operation |
title_full_unstemmed | The Stop Signal Task for Measuring Behavioral Inhibition in Mice With Increased Sensitivity and High-Throughput Operation |
title_short | The Stop Signal Task for Measuring Behavioral Inhibition in Mice With Increased Sensitivity and High-Throughput Operation |
title_sort | stop signal task for measuring behavioral inhibition in mice with increased sensitivity and high-throughput operation |
topic | Behavioral Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8696275/ https://www.ncbi.nlm.nih.gov/pubmed/34955779 http://dx.doi.org/10.3389/fnbeh.2021.777767 |
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