Foxp2 Is Required for Nucleus Accumbens-mediated Multifaceted Limbic Function.

Area of Science:

• Neuroscience
• Molecular Biology
• Behavioral Science

Background:

• The forkhead box protein P2 (Foxp2) is crucial for neural development, particularly speech and language.
• Its role in adult brain physiology, especially in the nucleus accumbens (NAc), is not well understood.
• Previous research focused on developmental roles, leaving a gap in knowledge regarding adult brain functions.

Purpose of the Study:

• To investigate the physiological function of Foxp2 in the NAc of adult mouse brains.
• To determine the impact of Foxp2 deficiency in the NAc on limbic-associated behaviors.
• To elucidate the specific roles of Foxp2 in social novelty, reward learning, and fear conditioning.

Main Methods:

• Conditional knockout of Foxp2 in the NAc medial shell using AAV-EGFP-Cre microinjections in Foxp2 floxed mice.
• Immunostaining to assess neuronal activity (c-Fos expression) in the NAc.
• Unbiased behavioral profiling to evaluate social novelty, appetitive reward learning, and fear learning/extinction.

Main Results:

• Foxp2 deficiency in the NAc led to increased basal c-Fos expression, indicating altered neuronal activity.
• Foxp2 cKO mice showed impaired social novelty, failing to distinguish between familiar and novel mice.
• Abnormalities were observed in appetitive reward learning and fear conditioning, including altered freezing responses and fear extinction.

Conclusions:

• Foxp2 plays a significant physiological role in the NAc of adult brains.
• Foxp2 in the NAc is critical for regulating social behavior, reward learning, and fear responses.
• Conditional knockout of Foxp2 in the NAc does not affect locomotion, motor coordination, or anxiety-like behaviors.