Prefrontal cortical NR2B-containing NMDA receptors are essential for spatial working memory performance

Area of Science:

• Neuroscience
• Cognitive Neuroscience
• Neuropharmacology

Background:

• N-methyl-D-aspartate (NMDA) receptor subunits NR2A and NR2B are key components of glutamate receptors.
• NR2B-containing NMDA receptors are localized in the prefrontal cortex (PFC) and implicated in working memory.
• Direct evidence for the necessity of PFC NR2B in working memory, particularly in non-human primates, was lacking.

Purpose of the Study:

• To investigate the necessity of prefrontal cortex (PFC) synaptic NR2B for working memory in rats and monkeys.
• To provide direct behavioral and neuropharmacological evidence for the role of PFC NR2B in working memory.

Main Methods:

• Examined synaptosome expression ratio of NR2B/2A in PFC, hippocampus, and visual cortex.
• Administered intra-PFC blockade of NR2B.
• Assessed performance in spatial working memory and pattern discrimination tasks.

Main Results:

• Confirmed a higher NR2B/2A expression ratio in the PFC compared to other brain regions in both species.
• Intra-PFC NR2B blockade robustly impaired spatial working memory in a delay-dependent manner in both rats and monkeys.
• Pattern discrimination performance remained unaffected by NR2B blockade.

Conclusions:

• PFC NR2B-containing NMDA receptors are critical for spatial working memory.
• These findings provide crucial evidence for the role of PFC NR2B in working memory, extending to non-human primates.