Objectives: 

Nitric oxide (NO) has been identified as an important neuromodulator of global cortical function. During the sleep-wake cycle, the subcortical activating ascending systems induce a massive cortical activation. It has been suggested that NO is a key substance in this activation. The aim of this work was to measure the temporal dynamics of cortical NO levels after the induced activation of cortical neurons.

Materials: 

We used optical spectroscopy (tissue absorption between 600 and 700 nm) in order to measure methemoglobin (metHb) levels (an NO marker), as well as oxyhemoglobin (oxyHb) and deoxyhemoglobin (deoxyHb) levels. Also, NO production was blocked by means of systemic injection of 7-nitroindazole (7NI). Cortical metHb concentration was monitored in the somatosensory cortex (SSC) of anesthetized (isoflurane) and paralyzed (gallamine) adult cats before and after the electrical stimulation of: 1) the nucleus basalis of Meynert of the basal forebrain (BF) and, 2) the peribrachial region of the brainstem (BS). Electrical stimulation was administered by train pulses (50 Hz, 2 s) delivered at different intensities (2 - 15 V, up to 1.5 mA) through bipolar electrodes located in BS and BF. These protocols were repeated after the application of 7NI (3.5 mg/kg, i.v.). The global SSC activity was monitored by means of an electrocorticogram (ECoG) obtained through a bipolar concentric electrode.

Results: 

Stimulation in both regions (BF and BS) induced a biphasic change in metHb: an initial transient increase followed by a slow and sustained decrease. The application of 7NI suppressed those changes and also diminished the basal levels of NO. The effect of such blockade was also evident in the ECoG.

Conclusions: 

These measurements of NO levels in vivo strongly reinforce the hypothesis that NO is a key substance in the global regulation of cortical activity, and indicate its role in the activation induced by the ascending systems.

Supported by Xunta de Galicia (INCITE09) and MICINN, Spain.