PSD-95 in CA1 Area Regulates Spatial Choice Depending on Age.

Area of Science:

• Neuroscience
• Cognitive Aging
• Synaptic Plasticity

Background:

• Cognitive functions, including spatial memory, depend on hippocampal synaptic plasticity.
• Aging impairs hippocampal function, altering spatial choice behavior.
• The molecular mechanisms underlying age-related cognitive decline are not fully understood.

Purpose of the Study:

• To investigate how aged mice make spatial choices compared to young mice.
• To examine the role of synaptic plasticity, specifically PSD-95, in age-related spatial decision-making.
• To identify alternative behavioral and molecular strategies employed by aged animals.

Main Methods:

• Utilized the IntelliCage system to assess spatial choice behavior in young and aged female mice.
• Analyzed dendritic spine morphology and PSD-95 expression in the dorsal CA1 (dCA1) hippocampus as indicators of synaptic plasticity.
• Employed shRNA to deplete PSD-95 in the dCA1 to assess its functional impact on spatial choices.

Main Results:

• Spatial choice training induced dendritic spine shrinkage and PSD-95 downregulation in young mice's dCA1.
• PSD-95 depletion in young mice impaired correct spatial choices but not reward preference.
• Aged mice exhibited perseverative behavior and social interaction, preferring a specific reward corner, independent of PSD-95 levels.

Conclusions:

• Young mice require PSD-95-dependent synaptic plasticity in dCA1 for accurate spatial choices.
• Aged mice utilize alternative strategies, including social observation and fixed corner preference, which are resilient to PSD-95 depletion.
• Cognitive strategies and the reliance on specific molecular pathways for spatial choice change significantly with age.