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The Journal of Neuroscience, May 15, 2003, 23(10):4299-4307

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Nitric Oxide-Mediated Cortical Activation: A Diffuse Wake-Up System

Jorge Mariño and Javier Cudeiro

Neuroscience and Motor Control Group (NEUROcom), Department Medicina and Instituto Nacional Educacion Fisica Galicia, 15006A Coruña, Spain

Nitric oxide (NO) has been implicated in some of the central pathways engaged in the regulation of the sleep–wake cycle. The existence of nitric oxide synthase (NOS) in the cholinergic basal forebrain (BF) cells projecting to the cortex suggests a role for NO in the activation induced by the BF during arousal. We tested, in the anesthetized cat, the hypothesis that inhibition of NOS would decrease the ability of BF cholinergic fibers to induce cortical activation. In control conditions, BF stimulation evoked an awake-like EEG pattern (i.e., a decrease in the low-frequency–high-amplitude oscillatory activity and an increase in the high-frequency–low-amplitude activity). After blocking NOS activity, the capacity of BF stimulation to induce cortical activation was strongly impaired. Furthermore, voltammetric measurements of NO levels revealed an increase in cortical NO after BF stimulation, also blocked by systemic NOS inhibition. These results indicate that the blockade of NOS activity significantly reduces the ability of BF stimulation to induce changes in the EEG pattern and suggest a role for NO in the BF–cholinergic system implicated in arousal mechanisms.

Key words: basal forebrain; sleep–wake cycle; V1; ACh; nitro-arginine; 7-nitroindazole

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Received Dec. 2, 2002; revised Feb. 20, 2003; accepted Mar. 5, 2003.

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