Midlatency auditory-evoked responses: effect of scopolamine in the cat and implications for brain stem cholinergic...

The objective of this study has been to define the role of cholinergic mechanisms in the generation of "wave A," a middle latency auditory-evoked potential recorded as a positivity with a 20-25 ms peak latency from the vertex of conscious cats. Wave A and its generator system have particular significance as an experimental model of the human middle latency component "P1." Both the feline wave A and the human P1 are characterized by a long recovery cycle, disappearance during slow wave sleep, and reappearance during rapid eye movement (REM) sleep and during wakefulness. The orchestration of several phenomena of REM sleep are known to involve muscarinic cholinergic mechanisms in the brain stem. Therefore, middle latency auditory-evoked potentials were studied in awake cats before and after injection of a cholinergic antagonist, scopolamine. Wave A and the successive negative potential were abolished by scopolamine in a dose-dependent fashion. This effect occurred within 5-15 min and was spontaneously reversible within a few hours. Although individual subjects were differentially susceptible to lower doses of the drug, all six subjects in this study demonstrated a well-defined statistically significant response at higher doses of the drug. In addition, careful parametric baseline studies were performed in each cat to strengthen the evidentiary linkage between wave A as recorded from the vertex in these experiments and previous studies describing the origin and trajectory of wave A in the brainstem reticular formation and several regions of thalamus, including the intralaminar nuclei. Thus, we conclude that the production of wave A depends substantially on the postsynaptic activation of muscarinic cholinergic receptors whose cells of origin lie within the brainstem reticular formation.