The Journal of neuroscience : the official journal of the Society for Neuroscience
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Animal and human studies of sleep and learning have demonstrated that training on various tasks increases subsequent rapid eye movement (REM) sleep and phasic pontine-wave (P-wave) activity, followed by improvement in performance on the learned task. It is well documented that REM sleep deprivation after learning trials blocks the expected improvement in performance on subsequent retesting. Our aim was to test whether experimentally induced P-wave generator activation could eliminate the learning impairment produced by post-training REM sleep deprivation. ⋯ In contrast, the rats that received the carbachol microinjection and REM sleep deprivation demonstrated normal learning. These results demonstrate, for the first time, that carbachol-induced activation of the P-wave generator prevents the memory-impairing effects of post-training REM sleep deprivation. This evidence supports our hypothesis that the activation of the P-wave generator during REM sleep deprivation enhances a physiological process of memory, which occurs naturally during post-training REM sleep.
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Spinal cord neurons release glycine and GABA and accumulate glycine receptors (GlyRs) and GABA(A) receptors in the same postsynaptic densities. In contrast, supramedullar neurons prefer GABA as a neurotransmitter and exclude GlyRs from postsynaptic anchoring. The general aim of the present study was to elucidate the mechanisms underlying transmitter-appropriate receptor accumulation at inhibitory synapses. ⋯ Accordingly in SCNs, GFP-tagged C5-gephyrin displayed a preferential postsynaptic accumulation opposite GABAergic synapses. Comparison of glycinergic, mixed, and GABAergic synapses in SCNs showed that the degree of GlyR accumulation was inversely related to the amount of postsynaptic C5-gephyrin. These results identify the C5 splice variant of gephyrin as a factor regulating the transmitter-appropriate degree of GlyR accumulation at inhibitory synapses.
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Previous work from our laboratory indicated that female Wistar rats will self-administer ethanol (EtOH) directly into the posterior ventral tegmental area (VTA). These results suggested that VTA dopamine (DA) neurons might be involved in mediating the reinforcing actions of EtOH within this region. The objectives of this study were to determine (1) the dose-response effects for the self-administration of EtOH into the VTA of male Wistar rats, and (2) the involvement of VTA DA neurons in the reinforcing actions of EtOH within the VTA. ⋯ Male Wistar rats self-infused 100-300 mg% EtOH directly into the posterior, but not anterior, VTA. Coadministration of quinpirole prevented the acquisition and extinguished the maintenance of EtOH self-infusion into the posterior VTA, and addition of sulpiride reinstated EtOH self-administration. The results of this study indicate that EtOH is reinforcing within the posterior VTA of male Wistar rats and suggest that activation of VTA DA neurons is involved in this process.
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Binding of the transcription factor nuclear factor E2-related factor 2 (Nrf2) to the antioxidant response element (ARE) in neural cells results in the induction of a battery of genes that can coordinate a protective response against a variety of oxidative stressors. In this study, tert-butylhydroquinone (tBHQ) and sulforaphane were used as activators of this pathway. Consistent with previous studies, treatment of primary cortical cultures from ARE reporter mice revealed selective promoter activity in astrocytes. ⋯ Microarray analysis was used to evaluate potential glial versus neuron-specific contributions to the neuroprotective effects of ARE activation and Nrf2 dependence. Strikingly, the change in neuronal gene expression after tBHQ treatment was dependent on Nrf2 activity in the astrocytes. This suggests that Nrf2-dependent genetic changes alter neuron-glia interactions resulting in neuroprotection.