Synaptic pruning in the female hippocampus is triggered at puberty by extrasynaptic GABAA receptors on dendritic spines
Adolescent synaptic pruning is thought to enable optimal cognition because it is disrupted in certain neuropathologies, yet the initiator of this process is unknown. One factor not yet considered is the α4βδ GABAA receptor (GABAR), an extrasynaptic inhibitory receptor which first emerges on dendriti...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2016-05-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/15106 |
| _version_ | 1811200206592540672 |
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| author | Sonia Afroz Julie Parato Hui Shen Sheryl Sue Smith |
| author_facet | Sonia Afroz Julie Parato Hui Shen Sheryl Sue Smith |
| author_sort | Sonia Afroz |
| collection | DOAJ |
| description | Adolescent synaptic pruning is thought to enable optimal cognition because it is disrupted in certain neuropathologies, yet the initiator of this process is unknown. One factor not yet considered is the α4βδ GABAA receptor (GABAR), an extrasynaptic inhibitory receptor which first emerges on dendritic spines at puberty in female mice. Here we show that α4βδ GABARs trigger adolescent pruning. Spine density of CA1 hippocampal pyramidal cells decreased by half post-pubertally in female wild-type but not α4 KO mice. This effect was associated with decreased expression of kalirin-7 (Kal7), a spine protein which controls actin cytoskeleton remodeling. Kal7 decreased at puberty as a result of reduced NMDAR activation due to α4βδ-mediated inhibition. In the absence of this inhibition, Kal7 expression was unchanged at puberty. In the unpruned condition, spatial re-learning was impaired. These data suggest that pubertal pruning requires α4βδ GABARs. In their absence, pruning is prevented and cognition is not optimal. |
| first_indexed | 2024-04-12T02:00:50Z |
| format | Article |
| id | doaj.art-e8cb1411acbe42308c8ffbb7b7a6893f |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:00:50Z |
| publishDate | 2016-05-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-e8cb1411acbe42308c8ffbb7b7a6893f2022-12-22T03:52:41ZengeLife Sciences Publications LtdeLife2050-084X2016-05-01510.7554/eLife.15106Synaptic pruning in the female hippocampus is triggered at puberty by extrasynaptic GABAA receptors on dendritic spinesSonia Afroz0Julie Parato1Hui Shen2Sheryl Sue Smith3https://orcid.org/0000-0003-4308-3267Department of Physiology and Pharmacology, SUNY Downstate Medical Center, Brooklyn, United States; Program in Neural and Behavioral Science, SUNY Downstate Medical Center, Brooklyn, United StatesDepartment of Physiology and Pharmacology, SUNY Downstate Medical Center, Brooklyn, United States; Program in Neural and Behavioral Science, SUNY Downstate Medical Center, Brooklyn, United StatesDepartment of Physiology and Pharmacology, SUNY Downstate Medical Center, Brooklyn, United States; School of Biomedical Engineering, Tianjin Medical University, Tianjin, ChinaDepartment of Physiology and Pharmacology, SUNY Downstate Medical Center, Brooklyn, United States; The Robert F. Furchgott Center for Neural and Behavioral Science, SUNY Downstate Medical Center, Brooklyn, United StatesAdolescent synaptic pruning is thought to enable optimal cognition because it is disrupted in certain neuropathologies, yet the initiator of this process is unknown. One factor not yet considered is the α4βδ GABAA receptor (GABAR), an extrasynaptic inhibitory receptor which first emerges on dendritic spines at puberty in female mice. Here we show that α4βδ GABARs trigger adolescent pruning. Spine density of CA1 hippocampal pyramidal cells decreased by half post-pubertally in female wild-type but not α4 KO mice. This effect was associated with decreased expression of kalirin-7 (Kal7), a spine protein which controls actin cytoskeleton remodeling. Kal7 decreased at puberty as a result of reduced NMDAR activation due to α4βδ-mediated inhibition. In the absence of this inhibition, Kal7 expression was unchanged at puberty. In the unpruned condition, spatial re-learning was impaired. These data suggest that pubertal pruning requires α4βδ GABARs. In their absence, pruning is prevented and cognition is not optimal.https://elifesciences.org/articles/15106GABA-A receptorhippocampuspubertydendritic spinesynaptic pruningdelta |
| spellingShingle | Sonia Afroz Julie Parato Hui Shen Sheryl Sue Smith Synaptic pruning in the female hippocampus is triggered at puberty by extrasynaptic GABAA receptors on dendritic spines eLife GABA-A receptor hippocampus puberty dendritic spine synaptic pruning delta |
| title | Synaptic pruning in the female hippocampus is triggered at puberty by extrasynaptic GABAA receptors on dendritic spines |
| title_full | Synaptic pruning in the female hippocampus is triggered at puberty by extrasynaptic GABAA receptors on dendritic spines |
| title_fullStr | Synaptic pruning in the female hippocampus is triggered at puberty by extrasynaptic GABAA receptors on dendritic spines |
| title_full_unstemmed | Synaptic pruning in the female hippocampus is triggered at puberty by extrasynaptic GABAA receptors on dendritic spines |
| title_short | Synaptic pruning in the female hippocampus is triggered at puberty by extrasynaptic GABAA receptors on dendritic spines |
| title_sort | synaptic pruning in the female hippocampus is triggered at puberty by extrasynaptic gabaa receptors on dendritic spines |
| topic | GABA-A receptor hippocampus puberty dendritic spine synaptic pruning delta |
| url | https://elifesciences.org/articles/15106 |
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