Inhibitory action of muscarinic agonists on neurons in the rat laterodorsal tegmental nucleus in vitro

J. I. Luebke, R. W. McCarley, R. W. Greene

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Abstract

1. The effects of the mixed cholinergic agonist carbachol and the muscarinic agonist methacholine (MCh) on neurons of the laterodorsal tegmental nucleus (LDT) were studied with the use of intracellular and whole- cell patch-clamp recordings in a rat brain stem slice preparation. 2. Neurons were classified into one of two categories on the basis of their intrinsic membrane properties: those that displayed a prominent low-threshold, calcium burst (LTB, 60%) and those that did not exhibit such a burst (non-LTB, 40%). 3. Neurons from which recordings were obtained were filled with biocytin, visualized with Texas-red avidin, and identified as cholinergic or noncholinergic with NADPH-diaphorase histochemistry. Eighty percent of the LTB neurons that were processed in this manner were cholinergic, and 60% of the non-LTB neurons were cholinergic. 4. Carbachol elicited a membrane hyperpolarization associated with a decrease in input resistance in 95% of the cells tested. Under voltage clamp this response was shown to be due to an outward current that reversed near the equilibrium potential for potassium and displayed marked inward rectification. The conductance/voltage relationship was fit to the Boltzmann equation with a mean V( 1/2 ) = -73 ± 4 (SD) mV and a mean k value of 10 ± 4. The carbachol-evoked current was fully blocked by extracellular barium. 5. There was no significant effect of carbachol on the transient currents I(A) or I(T). 6. The carbachol-evoked current was mimicked by the specific muscarinic agonist methacholine and blocked by high concentrations of the muscarinic receptor antagonist pirenzepine (IC50 = 580 nM). 7. These data indicate that the muscarinic agonist-evoked inhibition of LDT neurons is due to the activation of an inwardly rectifying potassium current mediated by a non-M1 muscarinic receptor. 8. These findings suggest an important role for acetylcholine in feedback inhibition of LDT neurons that play a prominent role in the generation of rapid eye movement (REM) sleep phenomenology. There is little or no activity in monoaminergic neurons during REM sleep, suggesting an absence of their inhibitory influence on highly active LDT neurons in this state. Hyperpolarization of bursting LDT neurons is needed to remove inactivation of the low-threshold calcium current so that bursting observed during REM sleep in association with pontogeniculooccipital (PGO) waves can occur. Evidence from this study suggests that a likely source of the requisite hyperpolarizing input on LDT neurons during REM sleep arises from a strong inhibitory feedback originating from cholinergic LDT neurons.

Original languageEnglish (US)
Pages (from-to)2128-2135
Number of pages8
JournalJournal of Neurophysiology
Volume70
Issue number5
Publication statusPublished - 1993

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ASJC Scopus subject areas

  • Physiology
  • Neuroscience(all)

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