title: Extrinsic and intrinsic substance P innervation of the rat lateral septal area calbindin cells.
abstract: The electrophysiological observations that substance P administration to the lateral septal area elicits both excitatory and inhibitory responses, together with earlier reports on the multiple sources of substance P innervation of the septum, implies that these axons with distinct origins have different functions. This prompted us to examine the origin and neurochemical character of substance P afferents to the lateral septal area. Chronic surgical isolation of the septum from its ventral afferents and retrograde tracer experiments using wheat germ agglutinin-conjugated horseradish peroxidase, both followed by an immunostaining for substance P, were employed to elucidate the origin of these axon terminals. In order to assess the possible co-existence of substance P with other neurotransmitter substances in the parent cells of the septopetal projections, co-localization studies for substance P and choline acetyltransferase, as well as substance P and GABA, were performed. The comparative distribution of substance P fibers and septal calbindin-containing neurons was also investigated using correlated light and electron microscopic double immunostaining. The results are summarized as follows: (i) the substance P innervation of the lateral septal area derives from several hypothalamic nuclei (including the lateral and lateroanterior hypothalamic area, tuber cinereum and ventromedial hypothalamic nucleus) and tegmental nuclei (the majority of fibers from the laterodorsal and a few from the pedunculopontine tegmental nucleus), as well as intrinsic septal cells; (ii) the septopetal substance P fibers of tegmental origin are cholinergic; intraseptal substance P neurons located in the dorsolateral part of the lateral septum also contain GABA, while substance P neurons seen on the border between the medial and lateral septal area and septopetal hypothalamic substance P cells do not contain GABA or acetylcholine; (iii) substance P fibers from pericellular baskets around calbindin-containing lateral septal neurons with a high degree of selectivity; (iv) approximately 90% of the entire calbindin cell population are postsynaptic targets of substance P axons; (v) their terminals contact the soma and the dendrites of these cells, among them the somatospiny neurons; and (vi) the extrinsic substance P boutons establish asymmetric, while the intrinsic substance P axon terminals form symmetric membrane specializations. Because neurons in the lateral septal area receive hippocampal input and project massively to hypothalamic areas, the different types of substance P input on these neurons can modify the information flow arriving from the hippocampus to diencephalic brain structures at the level of the lateral septal area.
authors.affiliation: Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, CT 06520-8063, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Szeidemann
authors.forename: R L
authors.initials: RL
authors.lastname: Jakab
authors.forename: M
authors.initials: M
authors.lastname: Shanabrough
authors.forename: C
authors.initials: C
authors.lastname: Leranth
mesh_terms: D000818:Animals; D001369:Axons / Q000648:ultrastructure; D005260:Female; D007031:Hypothalamus / Q000033:anatomy & histology; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D009434:Neural Pathways / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012686:Septal Nuclei / Q000378:metabolism*; D013373:Substance P / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D013373:Substance P; D005680:gamma-Aminobutyric Acid