MESOLIMBIC COMPONENT OF THE ASCENDING CHOLINERGIC PATHWAYS - ELECTROPHYSIOLOGICAL-PHARMACOLOGICAL STUDY

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 me chanism by which the cholinergic terminals initiate behavioral manifes tations is not clear. The objective of this study was to investigate t he effects of the ascending cholinergic projection from the laterodors al tegmental nucleus (LDT) on neuronal firing in the anterior hypothal amic-medial preoptic region(AHMP), known to be involved in agonistic b ehavior. Experiments were performed on urethan-anesthetized rats. Iont ophoretic application of carbachol (CCh) into the vicinity of single c ells in the AHMP caused a dose-dependent decrease in the mean firing r ate of 83% of units and an increase in 10% of units. The inhibitory ef fect of CCh, but not the excitatory effect, was reversed by iontophore tic pretreatment with scopolamine. The inhibition of the firing rate w as repeatable for the same dose of CCh and dose dependent. Electrical stimulation of neurons in the LDT caused a comparable, current-depende nt decrease in the mean firing rate of AHMP neurons that also was reve rsed by pretreatment of neurons in the AHMP with scopolamine. The anta gonizing effects of scopolamine were reversible with time. The same un its in the AHMP that inhibited their firing to stimulation of the LDT also responded with a similar inhibition to local iontophoretic CCh. F inally, the fluorescent carbocyanine dye, 4-(4-(dihexadecylamino)styry l)-N-methylpyridinium iodide, (DIA), has been used as a retrograde axo nal 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 mic roscopy. Results of the study suggest that LDT cholinergic neurons pro ject and terminate in the AHMP and that their activation causes a decr ease in the mean firing rate of the AHMP neurons. It is postulated tha t this inhibitory effect is implicated in the initiation of some of th e behavioral patterns like defensive or alarm vocalization and behavio ral inhibition.