Aplnr knockout mice display sex-specific changes in conditioned fear

Area of Science:

• Neuroscience
• Endocrinology
• Pharmacology

Background:

• The apelinergic system, comprising G-protein-coupled receptor APLNR and its ligands, is vital for development and homeostasis.
• APLNR's role in the central nervous system (CNS) remains largely uncharacterized.
• Targeting APLNR is a potential therapeutic strategy for cardiovascular and metabolic diseases.

Purpose of the Study:

• To investigate the function of the apelinergic system within the CNS.
• To elucidate the role of APLNR in sensory, motor, reward, social, learning, memory, and anxiety behaviors.
• To assess the impact of APLNR deficiency on fear-related behaviors.

Main Methods:

• Utilized a knockout mouse model lacking the Aplnr gene.
• Conducted comprehensive behavioral testing, including sensory ability, locomotion, reward and social preference, learning and memory, and anxiety paradigms.
• Analyzed acoustic startle response and conditioned fear responses.

Main Results:

• APLNR knockout significantly affected acoustic startle response.
• Sex-specific alterations in conditioned fear responses were observed in Aplnr knockout mice.
• Male Aplnr knockout mice exhibited heightened context- and cue-dependent fear responses, without changes in baseline anxiety.

Conclusions:

• The APLNR signaling pathway plays a significant role in modulating fear responses within the CNS.
• Findings suggest APLNR's involvement in fear memory and recall.
• Results support further investigation into APLNR-targeted therapies for CNS disorders, particularly PTSD.