EXTRINSIC AND INTRINSIC SUBSTANCE-P INNERVATION OF THE RAT LATERAL SEPTAL AREA CALBINDIN CELLS

The electrophysiological observations that substance P administration to the lateral septal area elicits both excitatory and inhibitory resp onses, together with earlier reports on the multiple sources of substa nce P innervation of the septum, implies that these axons with distinc t origins have different functions. This prompted us to examine the or igin and neurochemical character of substance P afferents to the later al septal area. Chronic surgical isolation of the septum from its vent ral afferents and retrograde tracer experiments using wheat germ agglu tinin-conjugated horseradish peroxidase, both followed by an immunosta ining for substance P, were employed to elucidate the origin of these axon terminals. In order to assess the possible co-existence of substa nce P with other neurotransmitter substances in the parent cells of th e septopetal projections, co-localization studies for substance P and choline acetyltransferase, as well as substance P and GABA, were perfo rmed. The comparative distribution of substance P fibers and septal ca lbindin-containing neurons was also investigated using correlated ligh t and electron microscopic double immunostaining. The results are summ arized as follows: (i) the substance P innervation of the lateral sept al area derives from several hypothalamic nuclei (including the latera l and lateroanterior hypothalamic area, tuber cinereum and ventromedia l hypothalamic nucleus) and tegmental nuclei (the majority of fibers f rom the laterodorsal and a few from the pedunculopontine tegmental nuc leus), as well as intrinsic septal cells; (ii) the septopetal substanc e P fibers of tegmental origin are cholinergic; intraseptal substance P neurons located in the dorsolateral parr 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 form pericellular baskets around calbindin-containing lateral septal neurons with a high degree of selectivity; (iv) approximately 90% of t he entire calbindin cell population are postsynaptic targets of substa nce P axons; (v) their terminals contact the soma and the dendrites of these cells, among them the somatospiny neurons; and (vi) the extrins ic substance P boutons establish asymmetric, while the intrinsic subst ance P axon terminals form symmetric membrane specializations. Because neurons in the lateral septal area receive hippocampal input and proj ect 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.