Generalized cortex activation by the auditory midbrain: mediation by acetylcholine and subcortical relays

The inferior colliculus (IC) is a critical component of the ascending projection system carrying auditory information from the brainstem to the forebrain. Recent evidence indicates that, in addition to its role in auditory processing, the IC can exert a generalized, modulatory effect on the forebrain by activating the neocortical electrocorticogram (ECoG). Given the sparse direct projections from the IC to the cortex, it appears that the effect of the IC to produce ECoG activation is indirect, mediated by one or several neuromodulatory systems that have diffuse access to the entire cortical mantle. However, the anatomical relays that permit the IC to influence cortical activity have not been elucidated. In the present experiments, electrical stimulation of the IC suppressed slow, large amplitude oscillations in the ECoG of urethane anesthetized rats, replacing them with higher-frequency cortical activation. This effect was blocked by the muscarinic receptor antagonist scopolamine (0.5–1.0 mg/kg, i.p.), suggestive of a critical role of acetylcholine (ACh) release. Consistent with this hypothesis, localized lidocaine infusions (2%, 1 μl) into the cholinergic basal forebrain complex strongly reduced ECoG activation elicited by IC stimulation. To identify additional relays between the IC and basal forebrain, the effects of lidocaine infusions into the superior colliculus, medial prefrontal cortex, midline thalamus, and dorsal raphe were also studied. Inactivation of the superior colliculus and dorsal raphe reduced IC-induced activation, while prefrontal cortex and thalamic infusions were ineffective. Concurrent basal forebrain and raphe inactivation produced effects similar to that of inactivation of the basal forebrain alone, suggesting that these two areas are arranged in series, rather than acting as independent, parallel pathways. These results suggest that the ability of the IC to induce ECoG activation is mediated, in large parts, by the basal forebrain cholinergic system. Consistent with anatomical evidence, the superior colliculus and dorsal raphe appear to provide important links to functionally connect the IC to the basal forebrain, allowing the IC to indirectly access the entire cortical mantle and enhance processing in neocortical networks.