Neocortical activation by electrical and chemical stimulation of the rat inferior colliculus: intra-collicular mapping and neuropharmacological characterization

Abstract

Classic experiments suggested that the midbrain reticular formation plays an important role in the induction and maintenance of high-frequency, low-amplitude activation of the electrocorticogram (ECoG). However, recent studies have shown that generalized activating systems are not restricted to the reticular formation in that non-reticular brain systems (e.g., basal forebrain, amygdala, superior colliculus) can effectively produce ECoG activation. Here, we investigated the role of the inferior colliculus (IC) in regulating ECoG activation in rats. Urethane-anesthetized rats displayed continuous large amplitude ECoG activity with peak power in the delta frequency range (0.5-3.9 Hz). Electrical 100-Hz stimulation (0.1-0.5 mA) of 40/88 (46%) stimulation sites in the IC suppressed low frequency oscillations and induced ECoG activation (>/=50% suppression of peak delta power). Systematic mapping of different IC territories (central nucleus, external and dorsal cortex) revealed that stimulation of all IC parts was equally effective in producing activation. Chemical stimulation of the IC with intra-collicular glutamate infusions (50 mM, 0.5 micro l) produces similar, but more consistent effects, with ECoG activation elicited in eight of nine rats. Pharmacological experiments were carried out in order to identify transmitters that mediate cortical activation in response to IC stimulation. The muscarinic receptor antagonist scopolamine (1 mg/kg, i.p.) reduced, but did not abolish, activation, as did the serotonergic receptor antagonist methiothepin (1 mg/kg, i.p.). A combination of the two drugs produced a complete block of IC-induced ECoG activation. These experiments demonstrate that the IC contains a distributed network, spanning all IC territories, which can participate in regulating the generalized activation state of the rat neocortex. Rather than by some direct cortical projections, IC neurons appear to induce ECoG activation by acting through both cholinergic and serotonergic systems, thought to provide the final effector mechanisms for cortical activation.