Electrical stimulation of the cholinergic laterodorsal tegmental nucleus elicits scopolamine-sensitive excitatory postsynaptic potentials in medial pontine reticular formation neurons

Abstract

A large and consistent body of data implicates mesopontine cholinergic neurons in the production of rapid eye movement sleep, and indicates that many rapid eye movement sleep events are mediated by activation of pontine reticular formation neurons. There is anatomical evidence for projections from the mesopontine cholinergic nuclei to the pontine reticular formation, but no study has shown that stimulation of this cholinergic zone produces excitatory postsynaptic potentials in pontine reticular formation neurons. In the present study, intracellular recordings were made from 168 pontine reticular formation neurons, identified by antidromic activation from the bulbar reticular formation and by neurobiotin intracellular labeling, in acutely anesthetized cats. The effects of single-pulse electrical stimulation of the laterordorsal tegmental nucleus portion of the ipsilateral mesopontine cholinergic zone were evaluated in these neurons. Under urethane anesthesia this stimulation produced, in 21 of 22 recorded neurons, long-latency excitatory postsynaptic potentials (mean = 3 ms), consistent with the conduction velocity of unmyelinated cholinergic fibers (measured conduction velocity was 2 m/s). This excitatory postsynaptic potential was virtually abolished by intravenous administration of the muscarinic cholinergic receptor blocker scopolamine ( n = 40 neurons), and by acute cuts separating the laterodorsal tegmental nucleus and the recorded neurons ( n = 40). In contrast, a short-latency excitatory postsynaptic potential (0.7–1.5 ms) was not reduced in amplitude by scopolamine and could still be elicited following acute transverse cuts. Unlike the longer-latency excitatory postsynaptic potential, its amplitude was not reduced by barbiturate anesthesia. These data, suggesting the presence of an excitatory, cholinergic laterodorsal tegmental nucleus projection to the pontine reticular formation, provide further support to other lines of evidence implicating mesopontine cholinergic neurons in the production of rapid eye movement sleep, and are compatible with a model of rapid eye movement sleep generation in which a key element is mesopontine cholinergic input depolarizing and increasing the excitability of reticular core neurons.