Superior colliculus stimulation enhances neocortical serotonin release and electrocorticographic activation in the urethane-anesthetized rat

Recent evidence indicates that the superior colliculus (SC), in addition to its functions in sensory detection, also participates in controlling the generalized activation state of the forebrain, as measured by the electroencephalogram (EEG) or electrocorticogram (ECoG). The mechanisms by which the SC modulates forebrain activation are not well understood. By using in vivo microdialysis, we examined the role of serotonin release as a mechanism by which the SC can control neocortical activity in the urethane-anesthetized rat. Electrical 100 Hz stimulation of the SC increased frontal cortex serotonin output to 116, 118, and 140% of baseline levels for stimulation intensities of 0.5, 0.75, and 1.0 mA, respectively. Further, 75% of extracellularly recorded single (putative serotonergic) dorsal raphe neurons increased their discharge rate in response to 100 Hz stimulation of the SC. Stimulation of the SC also suppressed frontal cortex low frequency (1-6 Hz) synchronized ECoG activity, replacing it with high-frequency desynchronization. This activation response was resistant to cholinergic-muscarinic receptor antagonists (atropine, 50 mg/kg; scopolamine, 2 mg/kg), but was reduced or abolished by systemic treatment with the serotonergic receptor antagonists ketanserin (10 mg/kg) or methiothepin (5 mg/kg). These data suggest that efferents from the SC, possibly by an excitatory action on serotonergic dorsal raphe cells, produce an enhanced release of serotonin and ECoG activation in the neocortex. The stimulation of cortical serotonin output may constitute a mechanism by which the SC acts on the forebrain to increase cortical excitability in response to sensory stimuli processed by SC neurons.