Ca2+-permeable AMPA receptors mediate induction of test pulse depression of naive synapses in rat visual cortical slices at early postnatal stage.

Synaptic depression in the hippocampus at early postnatal stage can be induced by test pulse stimulation (<1 Hz). However, the receptor mechanism for induction of this synaptic depression is unclear. In the present study, we used whole-cell patch clamp recording in vitro to investigate how excitatory and inhibitory synapses onto layer II/III pyramidal neurons of the primary visual cortex adapt to test pulse activation from a previously non-activated (naive) state. We found that excitatory postsynaptic currents (EPSCs) of pyramidal neurons were rapidly depressed by 0.1 Hz stimulation in acutely prepared slices from rats at 11-12 postnatal days, while this phenomena disappeared in slices from young adolescent rats (23-24 postnatal days). By contrast, inhibitory postsynaptic currents (IPSCs) were relatively stable following 0.1 Hz stimulation of rat slices at the same early postnatal stage. Moreover, the test pulse depression of EPSCs was associated with a decrease in 1/coefficient of variation (CV)(2) and no change in the paired-pulse ratio. These data imply silencing of synapses and no significant change either in postsynaptic receptor density or presynaptic terminal release probability. This synaptic depression was unaffected by the competitive NMDA receptor antagonist D-APV. Ca(2+)-permeable AMPA receptor selective antagonists, Naspm or IEM-1460, prevented the induction of the test pulse depression. These data suggest that EPSCs, but not IPSCs, were rapidly depressed by test pulse stimulation in rats at early postnatal stage via a Ca(2+)-permeable AMPA receptor-dependent mechanism.

Meng K ，Li YH ，Zhang L ，Li P ，Han TZ ... -  《-》

Selective blockade of Ca2+ permeable AMPA receptors in CA1 area of rat hippocampus.

Buldakova SL ，Kim KK ，Tikhonov DB ，Magazanik LG ... -  《NEUROSCIENCE》

Cortical injury affects short-term plasticity of evoked excitatory synaptic currents.

Li H ，Bandrowski AE ，Prince DA 《JOURNAL OF NEUROPHYSIOLOGY》

Modulation of AMPA receptor-mediated ion current by pituitary adenylate cyclase-activating polypeptide (PACAP) in CA1 pyramidal neurons from rat hippocampus.

Pituitary adenylate cyclase-activating polypeptide (PACAP), a neurotrophic and neuromodulatory peptide, was recently shown to enhance NMDA receptor-mediated currents in the hippocampus (Macdonald, et al. 2005. J Neurosci 25:11374-11384). To check if PACAP might also modulate AMPA receptor function, we tested its effects on AMPA receptor-mediated synaptic currents on CA1 pyramidal neurons, using the patch clamp technique on hippocampal slices. In the presence of the NMDA antagonist D-AP5, PACAP (10 nM) reduced the amplitude of excitatory postsynaptic currents (EPSCs) evoked in CA1 pyramidal neurons by stimulation of Schaffer collaterals. Following a paired-pulse stimulation protocol, the paired-pulse ratio was unaffected in most neurons, suggesting that the AMPA-mediated EPSC was modulated by PACAP mainly at a postsynaptic level. PACAP also modulated the currents induced on CA1 pyramidal neurons by applications of either glutamate or AMPA. The effects of PACAP were dose-dependent: at a 0.5 nM dose, PACAP increased AMPA-mediated current; such effect was blocked by PACAP 6-38, a selective antagonist of PAC1 receptors. The enhancement of AMPA-mediated current by PACAP 0.5 nM was abolished when cAMPS-Rp, a PKA inhibitor, was added to the intracellular solution. At a 10 nM concentration, PACAP reduced AMPA-mediated current; such effect was not blocked by PACAP 6-38. The inhibitory effect of 10 nM PACAP was mimicked by Bay 55-9837 (a selective agonist of VPAC2 receptors), persisted in the presence of intracellular BAPTA and was abolished by intracellular cAMPS-Rp. Stimulation-evoked EPSCs in CA1 neurons were significantly reduced following application of the PAC1 antagonist PACAP 6-38; this result indicates that PAC1 receptors in the CA1 region are tonically activated by endogenous PACAP and enhance CA3-CA1 synaptic transmission. Our results show that PACAP differentially modulates AMPA receptor-mediated current in CA1 pyramidal neurons by activation of PAC1 and VPAC2 receptors, both involving the cAMP/PKA pathway; the functional significance will be discussed in light of the multiple effects exerted by PACAP on the CA3-CA1 synapse at different levels.

Costa L ，Santangelo F ，Li Volsi G ，Ciranna L ... -  《-》

Presynaptic and postsynaptic modulation of glutamatergic synaptic transmission by activation of alpha(1)- and beta-adrenoceptors in layer V pyramidal neurons of rat cerebral cortex.

Adrenergic agonists have different modulatory effects on excitatory synaptic transmission depending on the receptor subtypes involved. The present study examined the loci of alpha(1)- and beta-adrenoceptor agonists, which have opposite effects on excitatory neural transmission, involved in modulation of glutamatergic transmission in layer V pyramidal cells of rat cerebral cortex. Phenylephrine, an alpha(1)-adrenoceptor agonist, suppressed the amplitude of AMPA receptor-mediated excitatory postsynaptic currents evoked by repetitive electrical stimulation (eEPSCs, 10 pulses at 33 Hz). The coefficient of variation (CV) of the 1st eEPSC amplitude and paired-pulse ratio (PPR), which were sensitive to extracellular Ca(2+) concentration, were not affected by phenylephrine. Phenylephrine suppressed miniature EPSC (mEPSC) amplitude without changing its frequency. In contrast, isoproterenol, a beta-adrenoceptor agonist, strongly increased the amplitude of the 1st eEPSC compared with that of the 2nd to 10th eEPSCs, which resulted in a decrease in PPR. Isoproterenol-induced enhancement of eEPSC amplitude was accompanied by a decrease in CV. Isoproterenol increased the frequency of mEPSCs without significant effect on amplitude. Phenylephrine suppressed inward currents evoked by puff application of glutamate, AMPA, or NMDA, whereas isoproterenol application was not accompanied by significant changes in these inward currents. These findings suggest that phenylephrine decreases eEPSCs through postsynaptic AMPA or NMDA receptors, while the effects of isoproterenol are mediated by facilitation of glutamate release from presynaptic terminals without effect on postsynaptic glutamate receptors. These two different mechanisms of modulation of excitatory synaptic transmission may improve the "signal-to-noise ratio" in cerebral cortex.

Kobayashi M ，Kojima M ，Koyanagi Y ，Adachi K ，Imamura K ，Koshikawa N ... -  《-》