Upregulated 5-HT1A receptor-mediated currents in the prefrontal cortex layer 5 neurons in the 15q11–13 duplication mouse model of autism
Abstract Serotonin (5-HT) is a well-known modulator of behavioral, physiological, and emotional functions of the forebrain region. We recently discovered alterations of serotonergic synaptic modulations in both, the prefrontal cortex (PFC) and the somatosensory cortex, in the 15q dup mouse model of...
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| Format: | Article |
| Language: | English |
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BMC
2020-08-01
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| Series: | Molecular Brain |
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| Online Access: | http://link.springer.com/article/10.1186/s13041-020-00655-9 |
| _version_ | 1818850435964862464 |
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| author | Fumihito Saitow Toru Takumi Hidenori Suzuki |
| author_facet | Fumihito Saitow Toru Takumi Hidenori Suzuki |
| author_sort | Fumihito Saitow |
| collection | DOAJ |
| description | Abstract Serotonin (5-HT) is a well-known modulator of behavioral, physiological, and emotional functions of the forebrain region. We recently discovered alterations of serotonergic synaptic modulations in both, the prefrontal cortex (PFC) and the somatosensory cortex, in the 15q dup mouse model of autism spectrum disorder (ASD). To further understand the roles of the 5-HT system implicated in developmental disorders such as ASD, comparison with model animals exhibiting different phenotypes may be useful. In this study, we investigated the relationship between sociability and the magnitude of 5-HT1A receptor (5-HT1AR) activation-induced outward currents from layer 5 pyramidal neurons in the PFC, because a mouse model of Williams-Beuren syndrome (WBS; another developmental disorder exhibiting low innate anxiety and high sociability) reportedly showed larger 5-HT-induced currents. To investigate whether the 5-HT1AR activation-induced outward currents are involved in the endophenotype determination of social behavior, we examined 15q dup mice with a phenotype opposite to WBS. We found 5-HT elicited significantly larger outward currents in 15q dup mice than in WT controls, regardless of sociability. In contrast, baclofen-induced GABAB receptor-mediated outward currents were not significantly different between genotypes, although GABAB receptor was coupled to Gi/o as well as 5-HT1A. Further, we found the larger 5-HT1AR-mediated currents in 15q dup mice did not affect the magnitude of inhibitory action of NMDA receptor functions. Taken together, our results provide a potential physiological hallmark for developmental disorders that may involve the imbalance of the neuronal circuity in the PFC. |
| first_indexed | 2024-12-19T06:49:06Z |
| format | Article |
| id | doaj.art-634f9f89495241d08d6916a859d2aad8 |
| institution | Directory Open Access Journal |
| issn | 1756-6606 |
| language | English |
| last_indexed | 2024-12-19T06:49:06Z |
| publishDate | 2020-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Brain |
| spelling | doaj.art-634f9f89495241d08d6916a859d2aad82022-12-21T20:31:48ZengBMCMolecular Brain1756-66062020-08-011311910.1186/s13041-020-00655-9Upregulated 5-HT1A receptor-mediated currents in the prefrontal cortex layer 5 neurons in the 15q11–13 duplication mouse model of autismFumihito Saitow0Toru Takumi1Hidenori Suzuki2Department of Pharmacology, Nippon Medical SchoolRIKEN Brain Science InstituteDepartment of Pharmacology, Nippon Medical SchoolAbstract Serotonin (5-HT) is a well-known modulator of behavioral, physiological, and emotional functions of the forebrain region. We recently discovered alterations of serotonergic synaptic modulations in both, the prefrontal cortex (PFC) and the somatosensory cortex, in the 15q dup mouse model of autism spectrum disorder (ASD). To further understand the roles of the 5-HT system implicated in developmental disorders such as ASD, comparison with model animals exhibiting different phenotypes may be useful. In this study, we investigated the relationship between sociability and the magnitude of 5-HT1A receptor (5-HT1AR) activation-induced outward currents from layer 5 pyramidal neurons in the PFC, because a mouse model of Williams-Beuren syndrome (WBS; another developmental disorder exhibiting low innate anxiety and high sociability) reportedly showed larger 5-HT-induced currents. To investigate whether the 5-HT1AR activation-induced outward currents are involved in the endophenotype determination of social behavior, we examined 15q dup mice with a phenotype opposite to WBS. We found 5-HT elicited significantly larger outward currents in 15q dup mice than in WT controls, regardless of sociability. In contrast, baclofen-induced GABAB receptor-mediated outward currents were not significantly different between genotypes, although GABAB receptor was coupled to Gi/o as well as 5-HT1A. Further, we found the larger 5-HT1AR-mediated currents in 15q dup mice did not affect the magnitude of inhibitory action of NMDA receptor functions. Taken together, our results provide a potential physiological hallmark for developmental disorders that may involve the imbalance of the neuronal circuity in the PFC.http://link.springer.com/article/10.1186/s13041-020-00655-95-HT1A receptorAutismDevelopmental disorderPrefrontal cortexSerotoninSynapse |
| spellingShingle | Fumihito Saitow Toru Takumi Hidenori Suzuki Upregulated 5-HT1A receptor-mediated currents in the prefrontal cortex layer 5 neurons in the 15q11–13 duplication mouse model of autism Molecular Brain 5-HT1A receptor Autism Developmental disorder Prefrontal cortex Serotonin Synapse |
| title | Upregulated 5-HT1A receptor-mediated currents in the prefrontal cortex layer 5 neurons in the 15q11–13 duplication mouse model of autism |
| title_full | Upregulated 5-HT1A receptor-mediated currents in the prefrontal cortex layer 5 neurons in the 15q11–13 duplication mouse model of autism |
| title_fullStr | Upregulated 5-HT1A receptor-mediated currents in the prefrontal cortex layer 5 neurons in the 15q11–13 duplication mouse model of autism |
| title_full_unstemmed | Upregulated 5-HT1A receptor-mediated currents in the prefrontal cortex layer 5 neurons in the 15q11–13 duplication mouse model of autism |
| title_short | Upregulated 5-HT1A receptor-mediated currents in the prefrontal cortex layer 5 neurons in the 15q11–13 duplication mouse model of autism |
| title_sort | upregulated 5 ht1a receptor mediated currents in the prefrontal cortex layer 5 neurons in the 15q11 13 duplication mouse model of autism |
| topic | 5-HT1A receptor Autism Developmental disorder Prefrontal cortex Serotonin Synapse |
| url | http://link.springer.com/article/10.1186/s13041-020-00655-9 |
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