Modulation Of AMPA Receptor Mediated Current By Nicotinic Acetylcholine Receptor In Layer I Neurons Of Rat Prefrontal Cortex

Object: Layer I neurons in the prefrontal cortex(PFC) exhibit extensive synaptic connections with deep layer neurons, implying their important role in the neural circuit. Study demonstrates that activation of nicotinic acetylcholine receptors(nAChRs) increases excitatory neurotransmission in this layer. The purpose of this study was to investigate the regulation of AMPA receptor mediated current in the layer I of rat prefrontal cortex, and to explore its potential mechanism.Methods: In the brain slice of 2 weeks-3weeks SD rat, whole cell patch clamp was used to record AMPA receptor mediated current and NMDA receptor mediated current at voltage clamp models in Layer I neurons in the prefrontal cortex. AMPA/NMDA ratio was calculated by AMPAR-mediated current relative to NMDAR-mediated current(NMDA current). Furthermore, to explore the potential mechanism of the augmentation of AMPAR current by nicotine, miniature excitatory postsynaptic current(mEPSC) and paired pulse ratio(PPR) was recorded when cells were voltage-clamped at-70 mV.Result: Bath perfusion of nicotine at 5μM,50Μm,500μM selectively enhanced the amplitude of AMPAR mediated current and AMPA/NMDA ratio, while without effects on NMDA receptor mediated current. When the neurons were voltage clamped at different potential(-70 mV,-40 mV,-20 mV,+20mV), nicotine can enhanced evoked-EPSC, while when voltage was clamped at +40mV and +60mV, respectively, the enhancement of evoked-EPSC became inconspicuous. Moreover, the augmentation of AMPAR current by nicotine was inhibited by a selective α7-nAChR antagonist methyllycaconitine, MLA(10nM) other than a selective α4β2-nAChR antagonist dihydro-β-erythroidine DhβE(1μM). Nicotine increased the frequency but not amplitude of mEPSC, MLA can block the increasement of mEPSC frequency by nicotine. Nicotine decreased the PPR, but PPR inhibition by nicotine is blocked by α7-nAChR antagonist MLA other than DhβE.Conclusion: Nicotine selectively enhance the amplitude of AMPAR mediated current and AMPA/NMDA ratio, while without effects on NMDA receptor mediated current in Layer I neurons of prefrontal cortex. And the augmentation of AMPA receptor mediated current is nicotine concentration-dependent. α7-nAChR was involved in the enhancement of AMPA receptor mediated current and AMPA/NMDA. Presynaptic α7-nAChR mediates nicotinic augmentation of glutamate release may be involved in the increasement of AMPA receptor mediated current.