[show abstract][hide abstract] ABSTRACT: Stimulation of presynaptic nicotinic acetylcholine receptors (nAChRs) increases the frequency of miniature excitatory synaptic activity (mEPSCs) to a point where they can promote cell firing in hippocampal CA3 neurons. We have evaluated whether nicotine regulation of miniature synaptic activity can be extended to inhibitory transmission onto striatal medium spiny projection neurons (MSNs) in acute brain slices. Bath application of micromolar nicotine typically induced 12-fold increases in the frequency of miniature inhibitory synaptic currents (mIPSCs). Little effect was observed on the amplitude of mIPSCs or mEPSCs under these conditions. Nicotine stimulation of mIPSCs was dependent on entry of extracellular calcium because removal of calcium from perfusate was able to block its action. To assess the potential physiological significance of the nicotine-stimulated increase in mIPSC frequency, we also examined the nicotine effect on evoked IPSCs (eIPSCs). eIPSCs were markedly attenuated by nicotine. This effect could be attributed to two potential mechanisms: transmitter depletion due to extremely high mIPSC rates and/or a reduction in presynaptic excitability associated with nicotinic depolarization. Treatment with low concentrations of K(+) was able to in part mimic nicotine's stimulatory effect on mIPSCs and inhibitory effect on eIPSCs. Current-clamp recordings confirmed a direct depolarizing action of nicotine that could dampen eIPSC activity leading to a switch to striatal inhibitory synaptic transmission mediated by tonic mIPSCs.
Journal of Neurophysiology 09/2007; 98(2):581-93. · 3.30 Impact Factor
[show abstract][hide abstract] ABSTRACT: We examined synaptic plasticity in the dentate gyrus (DG) of the hippocampus in vitro in juvenile C57Bl6 mice (28-40 days of age), housed in control conditions with minimal enrichment (Controls) or with access to an exercise wheel (Runners). LTP expression was significantly greater in slices from Runners than in those from Controls, but could be blocked by APV in both groups. LTP was significantly reduced by NR2B subunit antagonists in both groups. NVP-AAM077, an antagonist with a higher preference for NR2A subunits over NR2B subunits, blocked LTP in slices from Runners and produced a slight depression in Control animals. LTD in the DG was also blocked by APV, but not by either of the NR2B specific antagonists. Strikingly, NVP-AAM077 prevented LTD in Runners, but not in Control animals, suggesting an increased involvement of NR2A subunits in LTD in animals that exercise. NVP-AAM077 did not block LTD in NR2A Knock Out (KO) animals that exercised, as expected. In an attempt to discern whether NMDA receptors located at extrasynaptic sites could play a role in the induction of LTD, DL-TBOA was used to block excitatory amino acid transport and increase extracellular glutamate levels. Under these conditions, LTD was not blocked by the co-application of a specific NR2B subunit antagonist in either group, but NVP-AAM077 again blocked LTD selectively in Runners. These results indicate that NR2A and NR2B subunits play a significant role in LTP in the DG, and that exercise can significantly alter the contribution of NMDA NR2A subunits to LTD.