期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2016
卷号：113
期号：51
页码：14823-14828
DOI：10.1073/pnas.1614417113
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceThe human brain exhibits ongoing spontaneous activity characterized by very slow frequency fluctuations. These synchronously firing populations are considered to play a key role in conscious processes. We identified ultraslow fluctuations (USFs) in awake and anesthetized mice using two-photon imaging in the prefrontal cortex, a brain region involved in cognitive processes. Using transgenic mice, we demonstrate a crucial role for nicotinic acetylcholine receptors (nAChRs) in the generation of ultraslow fluctuations and their synchronicity, processes that are affected by deletion of nAChR subunits and general anesthetics like isoflurane. This work allows further dissection of the underlying mechanisms, and predicts that in humans with nAChR polymorphisms or copy number variation these processes might be altered, resulting in neuropsychiatric disorders. The prefrontal cortex (PFC) plays an important role in cognitive processes, including access to consciousness. The PFC receives significant cholinergic innervation and nicotinic acetylcholine receptors (nAChRs) contribute greatly to the effects of acetylcholine signaling. Using in vivo two-photon imaging of both awake and anesthetized mice, we recorded spontaneous, ongoing neuronal activity in layer II/III in the PFC of WT mice and mice deleted for different nAChR subunits. As in humans, this activity is characterized by synchronous ultraslow fluctuations and neuronal synchronicity is disrupted by light general anesthesia. Both the 7 and {beta}2 nAChR subunits play an important role in the generation of ultraslow fluctuations that occur to a different extent during quiet wakefulness and light general anesthesia. The {beta}2 subunit is specifically required for synchronized activity patterns. Furthermore, chronic application of mecamylamine, an antagonist of nAChRs, disrupts the generation of ultraslow fluctuations. Our findings provide new insight into the ongoing spontaneous activity in the awake and anesthetized state, and the role of cholinergic neurotransmission in the orchestration of cognitive functions.
