Impaired Cognitive Function after Perineuronal Net Degradation in the Medial Prefrontal Cortex

Area of Science:

• Neuroscience
• Extracellular Matrix Biology
• Cognitive Science

Background:

• Perineuronal nets (PNNs) are crucial extracellular matrix components ensheathing mature neurons in the central nervous system.
• PNNs regulate neuronal plasticity and are linked to neuronal stability, with their loss implicated in cognitive deficits.
• The specific impact of PNN loss in the medial prefrontal cortex (mPFC) on cognition remains underexplored.

Purpose of the Study:

• To investigate the direct behavioral consequences of PNN disruption in the rat mPFC.
• To determine if PNN loss in the mPFC affects specific cognitive functions, such as object recognition and perception.

Main Methods:

• Chondroitinase ABC (ChABC) enzyme was injected into the mPFC of Long-Evans rats to degrade PNNs.
• Behavioral assessments included object oddity perception, cross-modal object recognition (CMOR), prepulse inhibition (PPI), set-shifting (SS), reversal learning, and tactile/visual object recognition memory.
• Posthumous immunohistochemistry was used to confirm PNN reduction and correlate PNN density with behavioral performance.

Main Results:

• ChABC treatment significantly impaired performance on object oddity perception tasks.
• While not significantly different, ChABC-treated rats performed at chance levels in CMOR, unlike controls.
• No significant differences were observed in PPI, SS, reversal learning, or standard object recognition memory tasks.
• Reduced PNN density in the mPFC was confirmed, and higher PNN density predicted better performance on the oddity task.

Conclusions:

• PNN loss in the mPFC impairs specific cognitive functions, particularly object oddity perception.
• PNN density in the mPFC is a predictor of performance in certain cognitive tasks.
• These findings highlight the critical role of PNNs in supporting cognitive functions during young adulthood.