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Reveals that the permanent removal of axonal input to postsynaptic cells, assists in shaping the pattern of neuronal connections in response to experience. How research was conducted; Details on the nervous system's ability to respond to experience.

Abstract: The high potassium-induced potentiation of spontaneous glycine release in extracellular Ca2+-free conditions was studied in mechanically dissociated rat spinal dorsal horn neurons using whole-cell patch-clamp technique. Elevating extracellular K+ concentration reversibly increased the frequency of spontaneous glycinergic inhibitory postsynaptic currents (IPSCs) in the absence of extracellular Ca2+. Blocking voltage-dependent Na+ channels (tetrodotoxin) and Ca2+ channels (nifedipine and ω-grammotoxin-SIA) had no effect on this potassium-induced potentiation of glycine-release. The high potassium-induced increase in IPSC frequency was also observed in the absence of extracellular Na+, although the recovery back to baseline levels of release was prolonged under these conditions. The action of high potassium solution on glycine release was prevented by BAPTA-AM, by depletion of intracellular Ca2+ stores by thapsigargin and by the phospholipase C inhibitor U-73122. The results suggest that the elevated extracellular K+ concentration causes Ca2+ release from internal stores which is independent of extracellular Na+- and Ca2+-influx, and may reveal a novel mechanism by which the potassium-induced depolarization of presynaptic nerve terminals can regulate intracellular Ca2+ concentration and exocytosis. [Copyright &y& Elsevier]

Abstract: Retrograde synaptic signaling by endogenous cannabinoids (endocannabinoids) is a recently discovered form of neuromodulation in various brain regions. In hippocampus, it is well known that endocannabinoids suppress presynaptic inhibitory neurotransmitter release in CA1 region. However, endocannabinoid signaling in CA3 region remains to be examined. Here we investigated whether presynaptic inhibition can be caused by activation of postsynaptic group I metabotropic glutamate receptors (mGluRs) and following presynaptic cannabinoid receptor type 1 (CB1 receptor) using mechanically dissociated rat hippocampal CA3 pyramidal neurons with adherent functional synaptic boutons. Application of group I mGluR agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) reversibly suppressed spontaneous inhibitory postsynaptic currents (IPSCs). In the presence of tetrodotoxin (TTX), frequency of miniature IPSCs was significantly reduced by DHPG, while there were no significant changes in minimum quantal size and sensitivity of postsynaptic GABAA receptors to the GABAA receptor agonist muscimol, indicating that this suppression was caused by a decrease in GABA release from presynaptic nerve terminals. Application of CB1 synthetic agonist WIN55212-2 (mesylate(R)-(+)-[2,3-dihydro-5-methyl-3-[4-morpholino)methyl]pyrrolo-[1,2,3-de]-1,4-benzoxazin-6-yl](1-naphthyl)methanone) or endocannabinoid 2-arachidonoylglycerol also suppressed the spontaneous IPSC. The inhibitory effect of DHPG on spontaneous IPSCs was abolished by SR-141716 (5-(4-chlorophenyl)-1-(2,4-dichloro-phenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide), a CB1 receptor antagonist. Furthermore, postsynaptic application of GDP-βS blocked the DHPG-induced inhibition of spontaneous IPSCs, indicating the involvement of endcannabinoid-mediated retrograde synaptic signaling. These results provide solid evidence for retrograde signaling from postsynaptic group I mGluRs to presynaptic CB1 receptors, which induces presynaptic inhibition of GABA release in rat hippocampal CA3 region. [Copyright &y& Elsevier]

The modulatory effects of Zn[sup 2+] and other divalent cations on the ATP-induced responses of preganglionic neurons acutely dissociated from the rat dorsal motor nucleus of the vagus (DMV) were examined using a nystatin-perforated patch technique under voltage-clamp. DMV neurons were identified by back-filling of DiI placed on the vagal bundle at the neck. Zn[sup 2+] exerts a concentration-dependent effect on P2X receptor-mediated current (I[sub ATP]): a potentiation by low concentrations of Zn[sup 2+] (≤ 50 µm) and an inhibition by high concentrations (> 50 µm). Inhibition of the ATP response was associated with a prolongation of the rising phase of I[sub ATP]. Cu[sup 2+] mimicked Zn[sup 2+] regarding the biphasic modulation of I[sub ATP]. On the other hand, Ni[sup 2+] potentiated, but failed to inhibit, the ATP response even at a concentration of 3 mm. Quantitative RT-PCR revealed the similarity of P2X[sub 2] mRNA expression between the DMV and superior cervical ganglion (SCG) but not in the dorsal root ganglion (DRG) and hypoglossal nucleus (XII). The results from the electrophysiological and molecular approaches suggest that functional P2X receptors expressed in DMV neurons are characterized mainly by the P2X[sub 2] and P2X[sub 2/6] subtype. DMV neurons possess similar P2X receptor characteristics to SCG neurons. [ABSTRACT FROM AUTHOR]