Action of tachykinins in the hippocampus: facilitation of inhibitory drive to GABAergic interneurons.
By acting on neurokinin 1 (NK1) receptors, neuropeptides of the tachykinin family can powerfully excite rat hippocampal GABAergic interneurons located in the CA1 region and by this way indirectly inhibit CA1 pyramidal neurons. In addition to contact pyramidal neurons, however, GABAergic hippocampal interneurons can also innervate other interneurons. We thus asked whether activation of tachykinin-sensitive interneurons could indirectly inhibit other interneurons. The study was performed in hippocampal slices of young adult rats. Synaptic events were recorded using the whole-cell patch clamp technique. We found that substance P enhanced GABAergic inhibitory postsynaptic currents in a majority of the interneurons tested. Miniature, action potential-independent inhibitory postsynaptic currents were unaffected by substance P, as were evoked inhibitory synaptic currents. This suggests that the peptide acted at the somatodendritic membrane of interneurons, rather than at their axon terminals. The effect of substance P was mimicked by a selective NK1 receptor agonist, but not by neurokinin 2 (NK2) or neurokinin 3 (NK3) receptor agonists, and was suppressed by a NK1 selective receptor antagonist. In contrast to substance P, oxytocin, another peptide capable of activating hippocampal interneurons, had no effect on the inhibitory synaptic drive onto interneurons. We conclude that tachykinins, by acting on NK1 receptors, can influence the hippocampal activity by indirectly inhibiting both pyramidal neurons and GABAergic interneurons. Depending on the precise balance between these effects, tachykinins may either activate or depress hippocampal network activity.
Ogier
R
R
Sanofi-Aventis Suisse, CH-1217 Meyrin, Geneva, Switzerland.
Wrobel
L J
LJ
Raggenbass
M
M
D000200:Action Potentials / Q000187:drug effects; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D006624:Hippocampus / Q000166:cytology*; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects; D007395:Interneurons / Q000187:drug effects*; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D009433:Neural Inhibition / Q000187:drug effects*; D010121:Oxytocin / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D017966:Pyramidal Cells / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018039:Receptors, Tachykinin / Q000819:agonists; D013373:Substance P / Q000494:pharmacology; D015320:Tachykinins / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000779:Anesthetics, Local; D018039:Receptors, Tachykinin; D015320:Tachykinins; D013373:Substance P; D013779:Tetrodotoxin; D010121:Oxytocin; D005680:gamma-Aminobutyric Acid; C013411:biocytin; D008239:Lysine