221 92 92 3 3 Robert L. Jakab Csaba Leranth Department of Obstetrics and Gynecology Yale University, School of Medicine 333 Cedar Street 06510 New Haven CT USA Section of Neurobiology Yale University, School of Medicine 333 Cedar Street 06510 New Haven CT USA Summary In the lateral septal area (LSA), both inhibitory and excitatory dopamine (DA) actions, as well as hypothalamic and midbrain DA efferents, have been described. Some neurons of the hypothalamic and midbrain DA systems contain somatostatin (SOM) or neurotensin (NT), and, in the LSA, the distribution of fibers containing these peptides overlaps with DA fibers. These data prompted us to test for the presence of SOM and NT in LSA dopaminergic axon terminals of hypothalamic and midbrain origins. To verify the origins of SOM and NT innervation of the LSA, the retrograde tracer horseradish peroxidase conjugated with wheat germ agglutinin (HRP-WGA) was injected into the LSA, and alternate brain sections were immunostained for SOM, NT, or tyrosine hydroxylase (TH) in group 1 rats. Numerous retrogradely labeled neurons were found immunopositive for SOM in the periventricular and basolateral hypothalamus, many HRP-WGA labeled cells contained NT immunoreactivity in the ventral tegmental area, and TH-immunoreactive retrogradely labeled neurons were observed in both brain areas. In a new approach, the presence of these peptides in dopaminergic boutons was assessed by combining peptide immunocytochemistry with acute 6-hydroxydopamine (6-OHDA) induced lesioning of DA cell groups. These groups of rats were treated with desipramine to protect the noradrenergic fibers, and 45 min later 1 μg 6-OHDA (in 0.5 μl saline) was unilaterally injected into the periventricular hypothalamus ( group 2 ) or the ventral tegmental area ( group 3 ). After 48 h the rats were killed and alternate septal sections of both groups were immunostained for TH, SOM, or NT. On the operated side of the LSA in both groups, electron microscopy revealed numerous axon terminals that were immunopositive for TH and contained autophagous cytolysosomes, an early sign of catecholamine fiber degeneration induced by 6-OHDA. In group 2 , phagosomecontaining boutons were found immunopositive for SOM, but not for NT; vice versa, in group 3 , only NT-positive degenerated boutons were detected. SOM and NT-positive degenerated axon terminals in both groups formed synaptic contacts with LSA neurons, in particular with somatospiny cells. On the contralateral side of the LSA, all of the axon terminals were intact. It has been shown that SOM exerts an inhibitory action, whereas NT has an excitatory effect on limbic area neurons. Thus, the results implicate that the differential peptide content of dopamine fibers marks their functional differences. It appears that LSA neurons receive double innervation from an inhibitory “somatostatinergic” DA system of the hypothalamus, and from an excitatory “neurotensinergic” DA system of the midbrain.
Experimental Brain Research – Springer Journals
Published: Jan 1, 1993
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