Effects Of Nicotine On Synaptic Plasticity In Layer â…  Neurons Of Prefrontal Cortex In Rats

Objective:To investigate the effects and mechanisms of nicotine onAMPA-R-mediated current,NMDA-R-mediated current and AMPA/NMDAratio in prefrontal cortical layer I interneurons in rats.Methods:In brain slices of SD rats (2weeks old), whole cell patch-clamptechniques were used to record AMPA-R and NMDAR-mediated currents,AMPAR-mediated inward rectification currents, respectively. And peakvalue of AMPA/NMDA ratio was measured accordingly.Results:1. Bath application of nicotine (5M) significantly increased theamplitude of AMPA-R-mediated current (P<0.05) and AMPA/NMDA ratio(P<0.05), without any effect on NMDA-R-mediated current (P>0.05).2. Bath application of nicotine led to a significant increase inrectification of AMPAR current (P<0.05) in both layer I interneurons andlayer V pyramidal neurons. In layer I neurons, the effect of nicotine on AMPA/NMDA ratio was blocked by the inhibitor of Ca2+-permeableAMPARs (CP-AMPARs) IEM-1460(50M).3. Calcium chelator BAPTA (10mM), but not NMDA receptorantagonist APV (50M), significantly reduced nicotine enhancement ofAMPAR/NMDAR ratio in layer I neurons.4. Nicotine enhancement of AMPA/NMDA ratio was blocked byinhibitors of CaMKII (KN62,15M), PKA (H89,10M), PKC(Ro318220,10M), but not by inhibitors of ERK and calcineurin.Accordingly, intracellular infusion of inhibitory peptides but not scrambledpeptides of CaMKII, PKA and PKC (200M in each) significantly reducednicotine effect on AMPA/NMDA ratios.Conclusions:1. Nicotine selectively increased the AMPA-R-mediated current andthe AMPA/NMDA ratio, but not NMDA-R-mediated current.2. Ca2+-permeable AMPARs(CP-AMPARs) were involved in thenicotine regulation of AMPA/NMDA ratio in layer I neurons.3. The enhancement of nicotine on the AMPA/NMDA ratio was Ca2+-dependent but not NMDA receptor-dependent.4. Cellular signaling CaMKII, PKA and PKC were involved innicotine regulation of AMPAR.