Btbd3 expression regulates compulsive-like and exploratory behaviors in mice.

Area of Science:

• Neuroscience
• Genetics
• Behavioral Science

Background:

• BTB/POZ domain-containing 3 (BTBD3) is a potential risk gene for obsessive-compulsive disorder (OCD).
• BTBD3 is a putative transcription factor involved in neural development and dendritic pruning.

Purpose of the Study:

• To investigate the role of BTBD3 in regulating neural circuits and behaviors relevant to OCD in mice.
• To determine if BTBD3 influences compulsive-like and exploratory behaviors.

Main Methods:

• Tested BTBD3 wild-type, heterozygous, and knockout mice for compulsive-like behaviors (barbering, wheel-running, probabilistic learning task) and exploratory behaviors (open field, digging, marble-burying).
• Administered fluoxetine and desipramine to assess their effects on barbering behavior.
• Quantified dendritic morphology in specific brain regions (anterior cingulate cortex, mediodorsal thalamus, hippocampus).
• Used viral-mediated knockdown of BTBD3 in the hippocampus.

Main Results:

• BTBD3 heterozygous and knockout mice exhibited excessive barbering, wheel-running, impaired goal-directed behavior, and reduced exploration.
• Fluoxetine reduced barbering in wild-type and heterozygous mice, but not in knockout mice.
• Dendritic morphology was largely unaltered, with only a modest increase in spine density in the anterior cingulate cortex of knockout mice.
• Whole hippocampal BTBD3 knockdown replicated the knockout phenotypes.

Conclusions:

• Hippocampal BTBD3 expression selectively modulates compulsive-like and exploratory behaviors.
• BTBD3 plays a critical role in the neural circuits underlying OCD-related behaviors.