Mesolimbic Component of the Ascending Cholinergic Pathways: Electrophysiological-Pharmacological Study

Abstract

Brudzynski, Stefan M., Ludmila Kadishevitz, and Xiao-Wen Fu. Mesolimbic component of the ascending cholinergic pathways: electrophysiological-pharmacological study. J. Neurophysiol. 79: 1675–1686, 1998. The cholinergic input from the pontomesencephalic cholinergic neurons to the diencephalic and basal forebrain structures has been implicated in a number of limbically controlled overt behaviors. The cellular mechanism by which the cholinergic terminals initiate behavioral manifestations is not clear. The objective of this study was to investigate the effects of the ascending cholinergic projection from the laterodorsal tegmental nucleus (LDT) on neuronal firing in the anterior hypothalamic-medial preoptic region (AHMP), known to be involved in agonistic behavior. Experiments were performed on urethan-anesthetized rats. Iontophoretic application of carbachol (CCh) into the vicinity of single cells in the AHMP caused a dose-dependent decrease in the mean firing rate of 83% of units and an increase in 10% of units. The inhibitory effect of CCh, but not the excitatory effect, was reversed by iontophoretic pretreatment with scopolamine. The inhibition of the firing rate was repeatable for the same dose of CCh and dose dependent. Electrical stimulation of neurons in the LDT caused a comparable, current-dependent decrease in the mean firing rate of AHMP neurons that also was reversed by pretreatment of neurons in the AHMP with scopolamine. The antagonizing effects of scopolamine were reversible with time. The same units in the AHMP that inhibited their firing to stimulation of the LDT also responded with a similar inhibition to local iontophoretic CCh. Finally, the fluorescent carbocyanine dye, 4-(4-(dihexadecylamino)styryl)-N-methylpyridinium iodide, (DiA), has been used as a retrograde axonal tracer and was injected into the recording sites immediately after the electrophysiological recordings. After 1 wk, DiA dye was found in numerous neurons in the LDT as shown by the fluorescence confocal microscopy. Results of the study suggest that LDT cholinergic neurons project and terminate in the AHMP and that their activation causes a decrease in the mean firing rate of the AHMP neurons. It is postulated that this inhibitory effect is implicated in the initiation of some of the behavioral patterns like defensive or alarm vocalization and behavioral inhibition.