The Journal of neuroscience : the official journal of the Society for Neuroscience
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The involvement of adenosine on the development of time-dependent reversal of long-term potentiation (LTP) by low-frequency stimulation (LFS) was investigated at Schaffer collateral-CA1 synapses of rat hippocampal slices. A train of LFS (2 Hz, 10 min, 1200 pulses) had no long-term effects on synaptic transmission but produced lasting depression of previously potentiated responses. This reversal of LTP (depotentiation) was observed when the stimulus was delivered
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Microneurography was used in healthy human subjects to record action potentials from unmyelinated nerve fibers (C units) in cutaneous fascicles of the peroneal nerve. Activity-dependent slowing (n = 96) and transcutaneous electrical thresholds (n = 67) were determined. Eight units were sympathetic efferents according to their responses to sympathetic reflex provocations. ⋯ Activity-dependent slowing was much more pronounced in mechano-insensitive than in mechano-responsive units, without overlap. Sympathetic efferent C units showed intermediate slowing, significantly different from CMH, and completely separate from CH and CM(i)H(i) units. The activity-dependent slowing of conduction provides evidence for different membrane attributes of different classes of C fibers in humans.
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Repeated treatment with psychostimulant drugs causes long-lasting behavioral sensitization and associated neuroadaptations. Although sensitization induced by a single psychostimulant exposure has also been reported, information on the behavioral and neurochemical consequences of a single psychostimulant exposure is sparse. Therefore, to evaluate whether behavioral sensitization evoked by single and repeated psychostimulant pretreatment regimens represent the same neurobiological phenomenon, the time-dependent expression of behavioral, neurochemical, and neuroendocrine sensitization after a single exposure to amphetamine was investigated in rats. ⋯ The hyperreactivity of dopaminergic nerve terminals appeared to parallel the development of locomotor sensitization, i.e., whereas hyperreactivity of accumbens dopaminergic terminals increased between 3 d and 3 weeks after treatment, the hyperreactivity of medial prefrontal dopaminergic terminals decreased. Pre-exposure to amphetamine also sensitized the hypothalamus-pituitary-adrenal axis response to amphetamine at 1 and 3 weeks, but not at 3 d after treatment. Because these data closely resemble those reported previously for repeated amphetamine pretreatment, it is concluded that a single exposure to amphetamine is sufficient to induce long-term behavioral, neurochemical, and neuroendocrine sensitization in rats.
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The p75 neurotrophin receptor (p75NTR) binds all known neurotrophins and has been suggested to either function as a coreceptor for the trk receptor tyrosine kinases or be involved in independent signaling leading to cell death. We have analyzed the effects of nerve growth factor (NGF) on the growth of cultured hippocampal pyramidal neurons and examined the possibility that the effects of NGF are mediated via generation of ceramide produced by neutral sphingomyelinase (N-SMase). During the initial hour of culture, the only detectable NGF receptor is p75NTR, which by comparative Western blot is expressed at 50- to 100-fold lower levels than on PC12 cells. ⋯ Finally, scyphostatin, a specific N-SMase inhibitor, blocks the effects of NGF. We propose that a neurotrophin-p75NTR-ceramide signaling pathway influences outgrowth of hippocampal neurons. This signaling role of p75NTR may be distinct from other signaling pathways that lead to apoptosis.
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Activation of the adenylyl cyclase-cAMP-protein kinase A (PKA) intracellular signaling cascade is necessary for long-term memory consolidation in brain regions such as the hippocampus. However, the role of the PKA cascade in the working memory functions of the prefrontal cortex (PFC) is unknown. The present study examined the effects of manipulating PKA activity in the PFC using the cAMP stereoisomers Sp-cAMPS and Rp-cAMPS, which activate and inhibit PKA, respectively. ⋯ These results indicate that activation of the PKA intracellular signaling cascade in the PFC impairs working memory performance. The current findings contrast with studies of long-term memory consolidation, in which inhibition of PKA with agents such as Rp-cAMPS impaired memory consolidation (Bernabeu et al., 1997; Bourtchouladze et al., 1998), whereas enhancement of the PKA pathway improved memory (Bernabeu et al., 1997; Barad et al., 1998). These results demonstrate that discrete cognitive processes subserved by different cortical regions are mediated by distinct intracellular mechanisms.