The PPC neurons modulate memory generalization via NR2B-type NMDA receptors in mice

Area of Science:

• Neuroscience
• Cognitive Science
• Behavioral Science

Background:

• Generalization is a key cognitive process for applying learned rules to novel situations.
• The posterior parietal cortex (PPC) is implicated in abstract rule extraction, but its role in generalization is unclear.

Purpose of the Study:

• To investigate the neural mechanisms of memory generalization in mice.
• To determine the role of the PPC and specific receptor types in generalization.

Main Methods:

• Developed a five-hole operant paradigm to assess generalization in mice.
• Utilized fiber photometry to monitor PPC neuronal activity.
• Employed chemogenetics to inhibit PPC neurons and local infusions of receptor antagonists (NMDA, AMPA, acetylcholine) into the PPC.

Main Results:

• Mice showed robust memory generalization with graded success rates.
• PPC neurons were selectively activated during correct generalization choices.
• PPC inhibition and NMDA receptor antagonism, specifically NR2B subunits, impaired generalization, especially in difficult tasks.

Conclusions:

• PPC neurons are essential for memory generalization in mice.
• NR2B-containing NMDA receptors in the PPC play a critical role in this cognitive function.
• These findings elucidate circuit and molecular mechanisms underlying adaptive behavior.