Somatostatin depresses GABA receptor-mediated inhibition in the rat dorsolateral septal nucleus.
The effect of somatostatin-14 (SS-14) on gamma-aminobutyric acid (GABA)-mediated inhibitory neurotransmission in the dorsolateral septal nucleus (DLSN) was investigated using a submerged slice preparation and intracellular recording techniques. Somatostatin-14 applied by superfusion or by pressure ejection from micropipettes predominantly inhibited the intracellularly recorded fast inhibitory postsynaptic potential (fIPSP) and late hyperpolarizing potential (LHP) elicited by focal electrical stimulation of the DLSN. The decreases in LHP and fIPSP amplitude occurred at low concentrations of peptide, in the absence of appreciable changes in the passive-membrane properties of postsynaptic neurons, and outlasted the membrane hyperpolarizing effect produced by SS-14 at higher concentrations. The ability of SS-14 to modulate postsynaptic GABA receptor responses underlying the fIPSP and LHP were investigated by applying baclofen, a selective GABAB receptor agonist, and isoguvacine, a selective GABAA receptor agonist, by pressure ejection. Hyperpolarizing responses to GABAA and GABAB receptor stimulation were significantly decreased during superfusion of SS-14. Tetrodotoxin applied by superfusion blocked electrically evoked synaptic potentials but not the depressant effect of SS-14 on baclofen- or isoguvacine-induced hyperpolarization. Facilitation of the fIPSP or LHP by SS-14 also occurred but less frequently and consistently than the depressant action. Excitatory postsynaptic potentials and membrane response to NMDA or quisqualate appeared unaltered by bath-applied SS-14. These findings suggest a novel postsynaptic action of SS-14 leading to depression of synaptic responses mediated by GABAA and GABAB receptors. Synaptically released SS-14 in the DLSN may participate in modulation of feedforward and/or feedback inhibitory mechanisms coordinating DLSN function in the septo-hippocampal system.
Twery
M J
MJ
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston 77550.
Gallagher
J P
JP
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D066298:In Vitro Techniques; D007539:Isonicotinic Acids / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D013004:Somatostatin / Q000494:pharmacology*; D013569:Synapses / Q000502:physiology; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D007539:Isonicotinic Acids; D011963:Receptors, GABA-A; D013004:Somatostatin; D005680:gamma-Aminobutyric Acid; D001418:Baclofen; C015300:isoguvacine