Obesogenic diet induces circuit-specific memory deficits in mice

Area of Science:

• Neuroscience
• Cognitive Science
• Metabolic Disorders

Background:

• Obesity is linked to cognitive deficits, particularly memory impairments.
• Adolescence is a critical period for brain development, making it vulnerable to obesogenic influences.
• Previous research showed high-fat diet (HFD)-induced memory deficits in periadolescent rodents are reversible via ventral hippocampus (vHPC) manipulation.

Purpose of the Study:

• To investigate the specific roles of vHPC efferent pathways to the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) in HFD-induced memory impairments.
• To determine if chemogenetic inactivation of these pathways can rescue specific memory deficits in HFD-fed adolescent mice.

Main Methods:

• Utilized an intersectional viral approach in male mice fed an obesogenic high-fat diet (HFD).
• Chemogenetically inactivated specific vHPC efferent pathways (to NAc or mPFC) during memory tasks.
• Assessed memory performance (recognition and location) and behavioral measures (exploration, anxiety).

Main Results:

• HFD enhanced activation of vHPC-NAc and vHPC-mPFC pathways post-training; chemogenetics normalized this.
• Inactivation of the vHPC-NAc pathway rescued HFD-induced recognition memory deficits.
• Inactivation of the vHPC-mPFC pathway restored HFD-induced location memory deficits.
• Neither manipulation affected general exploration or anxiety-like behaviors.

Conclusions:

• Adolescent HFD intake impairs distinct memory types via overactivation of specific vHPC efferent pathways.
• Targeting the vHPC-NAc pathway shows potential for rescuing recognition memory.
• Targeting the vHPC-mPFC pathway may restore location memory.
• These findings highlight specific neural circuit targets for therapeutic intervention in diet-induced cognitive dysfunction.