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Btbd3 expression regulates compulsive-like and exploratory behaviors in mice
BTB/POZ domain-containing 3 (BTBD3) was identified as a potential risk gene in the first genome-wide association study of obsessive-compulsive disorder (OCD). BTBD3 is a putative transcription factor implicated in dendritic pruning in developing primary sensory cortices. We assessed whether BTBD3 al...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733800/ https://www.ncbi.nlm.nih.gov/pubmed/31501410 http://dx.doi.org/10.1038/s41398-019-0558-7 |
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author | Thompson, Summer L. Welch, Amanda C. Ho, Emily V. Bessa, João M. Portugal-Nunes, Carlos Morais, Mónica Young, Jared W. Knowles, James A. Dulawa, Stephanie C. |
author_facet | Thompson, Summer L. Welch, Amanda C. Ho, Emily V. Bessa, João M. Portugal-Nunes, Carlos Morais, Mónica Young, Jared W. Knowles, James A. Dulawa, Stephanie C. |
author_sort | Thompson, Summer L. |
collection | PubMed |
description | BTB/POZ domain-containing 3 (BTBD3) was identified as a potential risk gene in the first genome-wide association study of obsessive-compulsive disorder (OCD). BTBD3 is a putative transcription factor implicated in dendritic pruning in developing primary sensory cortices. We assessed whether BTBD3 also regulates neural circuit formation within limbic cortico-striato-thalamo-cortical circuits and behaviors related to OCD in mice. Behavioral phenotypes associated with OCD that are measurable in animals include compulsive-like behaviors and reduced exploration. We tested Btbd3 wild-type, heterozygous, and knockout mice for compulsive-like behaviors including cage-mate barbering, excessive wheel-running, repetitive locomotor patterns, and reduced goal-directed behavior in the probabilistic learning task (PLT), and for exploratory behavior in the open field, digging, and marble-burying tests. Btbd3 heterozygous and knockout mice showed excessive barbering, wheel-running, impaired goal-directed behavior in the PLT, and reduced exploration. Further, chronic treatment with fluoxetine, but not desipramine, reduced barbering in Btbd3 wild-type and heterozygous, but not knockout mice. In contrast, Btbd3 expression did not alter anxiety-like, depression-like, or sensorimotor behaviors. We also quantified dendritic morphology within anterior cingulate cortex, mediodorsal thalamus, and hippocampus, regions of high Btbd3 expression. Surprisingly, Btbd3 knockout mice only showed modest increases in spine density in the anterior cingulate, while dendritic morphology was unaltered elsewhere. Finally, we virally knocked down Btbd3 expression in whole, or just dorsal, hippocampus during neonatal development and assessed behavior during adulthood. Whole, but not dorsal, hippocampal Btbd3 knockdown recapitulated Btbd3 knockout phenotypes. Our findings reveal that hippocampal Btbd3 expression selectively modulates compulsive-like and exploratory behavior. |
format | Online Article Text |
id | pubmed-6733800 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-67338002019-09-10 Btbd3 expression regulates compulsive-like and exploratory behaviors in mice Thompson, Summer L. Welch, Amanda C. Ho, Emily V. Bessa, João M. Portugal-Nunes, Carlos Morais, Mónica Young, Jared W. Knowles, James A. Dulawa, Stephanie C. Transl Psychiatry Article BTB/POZ domain-containing 3 (BTBD3) was identified as a potential risk gene in the first genome-wide association study of obsessive-compulsive disorder (OCD). BTBD3 is a putative transcription factor implicated in dendritic pruning in developing primary sensory cortices. We assessed whether BTBD3 also regulates neural circuit formation within limbic cortico-striato-thalamo-cortical circuits and behaviors related to OCD in mice. Behavioral phenotypes associated with OCD that are measurable in animals include compulsive-like behaviors and reduced exploration. We tested Btbd3 wild-type, heterozygous, and knockout mice for compulsive-like behaviors including cage-mate barbering, excessive wheel-running, repetitive locomotor patterns, and reduced goal-directed behavior in the probabilistic learning task (PLT), and for exploratory behavior in the open field, digging, and marble-burying tests. Btbd3 heterozygous and knockout mice showed excessive barbering, wheel-running, impaired goal-directed behavior in the PLT, and reduced exploration. Further, chronic treatment with fluoxetine, but not desipramine, reduced barbering in Btbd3 wild-type and heterozygous, but not knockout mice. In contrast, Btbd3 expression did not alter anxiety-like, depression-like, or sensorimotor behaviors. We also quantified dendritic morphology within anterior cingulate cortex, mediodorsal thalamus, and hippocampus, regions of high Btbd3 expression. Surprisingly, Btbd3 knockout mice only showed modest increases in spine density in the anterior cingulate, while dendritic morphology was unaltered elsewhere. Finally, we virally knocked down Btbd3 expression in whole, or just dorsal, hippocampus during neonatal development and assessed behavior during adulthood. Whole, but not dorsal, hippocampal Btbd3 knockdown recapitulated Btbd3 knockout phenotypes. Our findings reveal that hippocampal Btbd3 expression selectively modulates compulsive-like and exploratory behavior. Nature Publishing Group UK 2019-09-09 /pmc/articles/PMC6733800/ /pubmed/31501410 http://dx.doi.org/10.1038/s41398-019-0558-7 Text en © The Author(s) 2019 Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Thompson, Summer L. Welch, Amanda C. Ho, Emily V. Bessa, João M. Portugal-Nunes, Carlos Morais, Mónica Young, Jared W. Knowles, James A. Dulawa, Stephanie C. Btbd3 expression regulates compulsive-like and exploratory behaviors in mice |
title | Btbd3 expression regulates compulsive-like and exploratory behaviors in mice |
title_full | Btbd3 expression regulates compulsive-like and exploratory behaviors in mice |
title_fullStr | Btbd3 expression regulates compulsive-like and exploratory behaviors in mice |
title_full_unstemmed | Btbd3 expression regulates compulsive-like and exploratory behaviors in mice |
title_short | Btbd3 expression regulates compulsive-like and exploratory behaviors in mice |
title_sort | btbd3 expression regulates compulsive-like and exploratory behaviors in mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733800/ https://www.ncbi.nlm.nih.gov/pubmed/31501410 http://dx.doi.org/10.1038/s41398-019-0558-7 |
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