title: Neuronal bursting induced by NK3 receptor activation in the neonatal rat spinal cord in vitro.
abstract: Intracellular recording from lumbar motoneurons and extracellular recording from ventral roots of the neonatal rat isolated spinal cord were used to study the mechanisms responsible for the excitation mediated by NK3 tachykinin receptors. The selective NK3 agonists senktide or [MePhe7]neurokinin B induced a slow depolarization with superimposed oscillations (mean period +/- SD was 2.8 +/- 0.8 s) that, in the majority of cases, showed left-right alternation at segmental level and were synchronous between L2 and L5 of the same side. During agonist wash out (5-20 min) a delayed form of hyperexcitability emerged consisting of bursts lasting 8 +/- 2 s (average interburst interval 55 +/- 21 s) with superimposed oscillations usually with homosegmental alternation and heterosegmental synchronicity. Such bursting was accompanied by depression of GABAergic dorsal root potentials evoked by dorsal root stimulation and of the recurrent inhibitory postsynaptic potential recorded from motoneurons. Despite bursting, motoneuron membrane potential returned to baseline while input resistance was increased. Bursts were a network-dependent phenomenon triggered by previous NK3 receptor activation because bursting was suppressed by glutamate receptor antagonists and was insensitive to motoneuron membrane potential or subsequent application of an NK3 receptor antagonist. NK3 receptors operated synergistically with N-methyl-D-aspartate (NMDA) and 5-hydroxytryptamine (5-HT) to trigger fully alternating locomotor-like rhythms while NK3 receptor antagonism disrupted the same rhythm. In summary, in the neonatal rat spinal cord NK3 receptors could trigger rhythmic activity predominantly with alternation at segmental level but with synchronous coupling between ipsilateral motor pools. NK3 receptor activation could also facilitate fictive locomotor patterns induced by NMDA and 5-HT.
authors.affiliation: Biophysics Sector and Istituto Nazionale di Fisica della Materia Unit, International School for Advanced Studies (SISSA), 34014 Trieste, Italy. marche@sissa.it
authors.forename: C
authors.initials: C
authors.lastname: Marchetti
authors.forename: A
authors.initials: A
authors.lastname: Nistri
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D005071:Evoked Potentials / Q000187:drug effects; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D066298:In Vitro Techniques; D008124:Locomotion / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology; D015287:Neurokinin B / Q000031:analogs & derivatives* / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018042:Receptors, Neurokinin-3 / Q000819:agonists*; D013116:Spinal Cord / Q000166:cytology* / Q000187:drug effects; D013373:Substance P / Q000031:analogs & derivatives* / Q000494:pharmacology; D013618:Tachyphylaxis / Q000502:physiology
chemical_list: D010446:Peptide Fragments; D018042:Receptors, Neurokinin-3; C080394:neurokinin B, MePhe(7)-; C054724:senktide; D013373:Substance P; D015287:Neurokinin B