Genetic mapping identifies Homer1 as a developmental modifier of attention.
Saved in:
| Title: | Genetic mapping identifies Homer1 as a developmental modifier of attention. |
|---|---|
| Authors: | Gershon, Zachary (AUTHOR), Bonito-Oliva, Alessandra (AUTHOR), Kanke, Matt (AUTHOR), Terceros, Andrea (AUTHOR), Rankin, Genelle (AUTHOR), Fak, John (AUTHOR), Harada, Yujin (AUTHOR), Iannone, Andrew F. (AUTHOR), Gebremedhin, Millennium (AUTHOR), Fabella, Brian (AUTHOR), De Marco García, Natalia V. (AUTHOR), Sethupathy, Praveen (AUTHOR), Rajasethupathy, Priya (AUTHOR) |
| Source: | Nature Neuroscience. Mar2026, Vol. 29 Issue 3, p647-659. 13p. |
| Abstract: | The genetic factors and resulting neural circuit physiology driving variation in attention are poorly understood. Here we took an unbiased forward genetics approach to identify genes of large effect on attention. We studied 200 genetically diverse mice and, through genetic mapping, identified a small locus on chromosome 13 (95% CI 92.22–94.09 Mb) that is significantly associated with variation in pre-attentive processing. Within the locus we identified a gene, Homer1, encoding a synaptic protein, whose downregulation during development led to improvements in multiple measures of attention in adulthood. Mechanistically, reduced Homer1 levels resulted in an upscaling of GABA receptors and enhanced inhibitory tone in the prefrontal cortex, leading to improved neural signal to noise and attentional performance. We thus identify a single genetic locus of large effect on attention and propose Homer1-dependent inhibitory tone, sculpted during a developmental sensitive period, as a key regulator and potential therapeutic target for attentional performance. Genetic mapping in mice identified Homer1a as a key modifier of attention. Developmental downregulation in the prefrontal cortex enhances inhibitory tone, neural signal to noise and adult attentional performance, revealing a new control mechanism and target. [ABSTRACT FROM AUTHOR] |
| Copyright of Nature Neuroscience is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Psychology and Behavioral Sciences Collection |
| FullText | Text: Availability: 0 |
|---|---|
| Header | DbId: pbh DbLabel: Psychology and Behavioral Sciences Collection An: 192199486 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
| IllustrationInfo | |
| Items | – Name: Title Label: Title Group: Ti Data: Genetic mapping identifies Homer1 as a developmental modifier of attention. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Gershon%2C+Zachary%22">Gershon, Zachary</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Bonito-Oliva%2C+Alessandra%22">Bonito-Oliva, Alessandra</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Kanke%2C+Matt%22">Kanke, Matt</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Terceros%2C+Andrea%22">Terceros, Andrea</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Rankin%2C+Genelle%22">Rankin, Genelle</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Fak%2C+John%22">Fak, John</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Harada%2C+Yujin%22">Harada, Yujin</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Iannone%2C+Andrew+F%2E%22">Iannone, Andrew F.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Gebremedhin%2C+Millennium%22">Gebremedhin, Millennium</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Fabella%2C+Brian%22">Fabella, Brian</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22De+Marco+García%2C+Natalia+V%2E%22">De Marco García, Natalia V.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Sethupathy%2C+Praveen%22">Sethupathy, Praveen</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Rajasethupathy%2C+Priya%22">Rajasethupathy, Priya</searchLink> (AUTHOR) – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Nature+Neuroscience%22">Nature Neuroscience</searchLink>. Mar2026, Vol. 29 Issue 3, p647-659. 13p. – Name: Abstract Label: Abstract Group: Ab Data: The genetic factors and resulting neural circuit physiology driving variation in attention are poorly understood. Here we took an unbiased forward genetics approach to identify genes of large effect on attention. We studied 200 genetically diverse mice and, through genetic mapping, identified a small locus on chromosome 13 (95% CI 92.22–94.09 Mb) that is significantly associated with variation in pre-attentive processing. Within the locus we identified a gene, Homer1, encoding a synaptic protein, whose downregulation during development led to improvements in multiple measures of attention in adulthood. Mechanistically, reduced Homer1 levels resulted in an upscaling of GABA receptors and enhanced inhibitory tone in the prefrontal cortex, leading to improved neural signal to noise and attentional performance. We thus identify a single genetic locus of large effect on attention and propose Homer1-dependent inhibitory tone, sculpted during a developmental sensitive period, as a key regulator and potential therapeutic target for attentional performance. Genetic mapping in mice identified Homer1a as a key modifier of attention. Developmental downregulation in the prefrontal cortex enhances inhibitory tone, neural signal to noise and adult attentional performance, revealing a new control mechanism and target. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Nature Neuroscience is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
| PLink | https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=pbh&AN=192199486 |
| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1038/s41593-025-02155-2 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 13 StartPage: 647 Titles: – TitleFull: Genetic mapping identifies Homer1 as a developmental modifier of attention. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Gershon, Zachary – PersonEntity: Name: NameFull: Bonito-Oliva, Alessandra – PersonEntity: Name: NameFull: Kanke, Matt – PersonEntity: Name: NameFull: Terceros, Andrea – PersonEntity: Name: NameFull: Rankin, Genelle – PersonEntity: Name: NameFull: Fak, John – PersonEntity: Name: NameFull: Harada, Yujin – PersonEntity: Name: NameFull: Iannone, Andrew F. – PersonEntity: Name: NameFull: Gebremedhin, Millennium – PersonEntity: Name: NameFull: Fabella, Brian – PersonEntity: Name: NameFull: De Marco García, Natalia V. – PersonEntity: Name: NameFull: Sethupathy, Praveen – PersonEntity: Name: NameFull: Rajasethupathy, Priya IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 03 Text: Mar2026 Type: published Y: 2026 Identifiers: – Type: issn-print Value: 10976256 Numbering: – Type: volume Value: 29 – Type: issue Value: 3 Titles: – TitleFull: Nature Neuroscience Type: main |
| ResultId | 1 |
