Somatostatin hyperpolarizes neurons and inhibits spontaneous activity in the rat dorsolateral septal nucleus.

Intracellular recordings were made from rat brain neurons in a submerged slice preparation containing the dorsolateral septal nucleus (DLSN). Somatostatin-14 (SS-14) was applied to these neurons by superfusing solutions containing known concentrations of the peptide or by pressure ejection from micropipettes. With either method of treatment, SS-14 produced membrane hyperpolarization and decreased membrane resistance in a concentration-dependent manner. The hyperpolarizing response to SS-14 occurred in virtually all neurons tested and appeared to result from a direct action on DLSN neurons mediated by an increased permeability to potassium ions. The SS-14-induced membrane hyperpolarization was not blocked by naloxone, bicuculline, tetrodotoxin, or calcium-free, high-magnesium superfusion media. In a small number of neurons, SS-14 application produced a membrane depolarization which did not exhibit clear concentration-dependence and was blocked by superfusion of calcium-free, high-magnesium media indicating an indirect action. These findings reveal that SS-14 is a potent inhibitor of DLSN neurons in vitro and provide the first evidence that receptors for this putative neurotransmitter are located on postsynaptic neurons in this nucleus. Synaptically released SS-14 may play an important role in the modulation of septohippocampal function.