ausblenden:
Schlagwörter:
-
Zusammenfassung:
It is well-established that electrical or pharmacological activation of several nuclei in the reticular formation elicits cortical arousal which is reflected in the EEG as low amplitude and high frequency, or ‘desynchronized’, activity pattern. Among the ascending reticular activating system (ARAS) is the noradrenergic locus coeruleus (LC), which is critically involved in regulation of the sleep-wake cycle. Local activation of LC, as well as stimulation of its afferents, has been reported to induce cortical desynchronization. Interestingly, several nuclei of the ARAS have been shown to have either anatomical connections with LC or their activation showed impact on activity of LC neurons. Therefore, we hypothesized that the LC is a primary hub component in the ARAS. In order to test this hypothesis, we stimulated LC directly, by applying brief (100-200ms) trains of electrical pulses, or indirectly, by electrical stimulation of contralateral limb paw and simultaneously recorded local field potential (LFP) from multiple cortical and subcortical brain regions in urethane anesthetized rats. Both stimulation paradigms evoked transient (1-2 sec) desynchronization of the cortical LFP in all recorded sites, which were characterized by decreased LFP signal power within low frequency (1-8 Hz) and increased in high frequency range (>20 Hz). Foot shock evoked LFP desynchronization was completely abolished in all recording sites including the hid paw representation of the primary somatosensory cortex after bilateral, but not unilateral, selective inhibition of LC neurons by means of local iontophoretic injection of α2-agonist clonidine. Cortical desynchronization to nociceptive stimulation is used as an indicator of efficiency of analgesic treatment. Furthermore, clonidine is known to possess antinociceptive properties when used as additive in anesthetics. Therefore, our results demonstrate that LC is tightly involved in mediating nociception. The well-known antinociceptive property of α2-agonists in the peripheral nervous system is likely due to decreased levels of noradrenaline as result of the activation of presynaptic negative feedback of α2-receptors. The brain regions that mediate LC-dependent cortical desynchronization are yet to be identified.
