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Btbd3 expression regulates compulsive-like and exploratory behaviors in mice
- Source :
- Translational Psychiatry, Vol 9, Iss 1, Pp 1-14 (2019), Translational psychiatry, vol 9, iss 1, Repositório Científico de Acesso Aberto de Portugal, Repositório Científico de Acesso Aberto de Portugal (RCAAP), instacron:RCAAP, Translational Psychiatry
- Publication Year :
- 2019
- Publisher :
- Nature Publishing Group, 2019.
-
Abstract
- 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.<br />Brain Research Foundation seed grant (S.C.D.), a NARSAD Independent Investigator award (S.C.D.), R21-MH115395-01 (S.C.D.), Della Martin Foundation (J.A.K.), and training grants: T32 GM07839 (S.L.T.), and T32 DA07255 (S.L.T.).
- Subjects :
- Obsessive-Compulsive Disorder
Medicina Básica [Ciências Médicas]
Hippocampus
Hippocampal formation
Open field
Mice
0302 clinical medicine
Desipramine
Psychology
Mice, Knockout
0303 health sciences
Gene knockdown
Behavior, Animal
Brain
Phenotype
Anxiety Disorders
Antidepressive Agents
Psychiatry and Mental health
medicine.anatomical_structure
Mental Health
Knockout mouse
Ciências Médicas::Medicina Básica
Compulsive Behavior
Public Health and Health Services
medicine.drug
Knockout
Clinical Sciences
Nerve Tissue Proteins
Biology
Motor Activity
Basic Behavioral and Social Science
Article
lcsh:RC321-571
03 medical and health sciences
Cellular and Molecular Neuroscience
Fluoxetine
Behavioral and Social Science
medicine
Animals
lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry
Biological Psychiatry
Anterior cingulate cortex
030304 developmental biology
Behavior
Science & Technology
Animal
Neurosciences
Brain Disorders
Disease Models, Animal
Disease Models
Exploratory Behavior
Nerve Net
Psychiatric disorders
Neuroscience
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 21583188
- Volume :
- 9
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Translational Psychiatry
- Accession number :
- edsair.doi.dedup.....5a4e9a5a257753dc54540041b4614658