The dorsolateral prefrontal cortex (DLPFC) is greatly influenced by arousal state, and is affected in disorders such as schizophrenia, where there are genetic insults in α7 nicotinic acetylcholine receptors (α7-nAChRs). A recent behavioral study indicates that ACh depletion from DLPFC markedly impairs working memory but little is known about how α7-nAChRs influence DLPFC cognitive circuits. DLPFC pyramidal cells excite each other through glutamatergic NMDA receptor synapses to generate persistent network firing in the absence of sensory stimulation. The authors of this study examine α7-nAChR localization and actions in primate DLPFC and find that they are enriched in glutamate network synapses, where they are essential for DLPFC persistent firing, with permissive effects on NMDA receptor actions. Blockade of α7-nAChRs markedly reduced, whereas low-dose stimulation selectively enhanced, neuronal representations of visual space. These findings in DLPFC contrast with the primary visual cortex, where nAChR blockade had no effect on neuronal firing. The authors show that α7-nAChR stimulation is needed for NMDA action, suggesting that it is highly important for engagement of DLPFC circuits. As ACh is released in cortex during waking but not during deep sleep, these findings may explain how ACh shapes differing mental states during wakefulness versus sleep. The authors suggest that these results may explain why genetic perturbation of α7-nAChRs would disrupt cognitive experience in schizophrenia.
Yang Y, Paspalas CD, Jin LE, Picciotto MR, Arnsten AFT, Wang M: Nicotinic α7 receptors enhance NMDA cognitive circuits in dorsolateral prefrontal cortex. PNAS [Epub ahead of print July 1, 2013, ].