Neuroscience
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Receptors for ATP have been reported on peripheral nerve terminals. It is a widespread assumption that the axonal membrane does not possess this kind of chemosensitivity, although P2X purinoceptors have been found in isolated rat vagus nerve. Therefore, in the present study, effects of ATP and analogues were tested on the excitability of unmyelinated axons in isolated rat sural nerve, mouse dorsal roots, and human sural nerve. ⋯ However, we could not detect P2X receptors in this preparation with our techniques. These data show that the ATP sensitivity of sensory neurones is not restricted to their terminals. Activation of axonal purinergic receptors may contribute to the transduction of sensory, including nociceptive, stimuli.
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We examined the effects of 4-aminopyridine (4-AP) on isolated horizontal (superficial, middle and deep) rat neocortical slices in order to study laminar synchronous network behavior directly. Application of 4-AP induced spontaneous synchronized activity in all of these types of slices. In middle and deep layer slices the activities were similar to those of coronal slices, consisting of periodic short- and long-duration discharges. ⋯ By contrast, conventional coronal slices showed robust spontaneous epileptiform discharges under these circumstances. In intact coronal slices focal 4-AP application in superficial layers induced spontaneous inhibitory GABAergic events, while delivery into deep layers led to epileptiform discharges. From these results we conclude that: (1) 4-AP-induced population discharges are driven by glutamatergic transmission in middle and deep layer horizontal slices, and by GABAergic transmission in superficial layers; (2) only superficial layers are capable of supporting synchronized GABAergic activity independent of excitatory amino acid transmission; (3) superficial layers do not sustain epileptiform activity in the absence of deep layer neurons; and (4) synchronized superficial networks can inhibit deep layer neuronal activity.
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Comparative Study
Decreased inflammatory pain due to reduced carrageenan-induced inflammation in mice lacking adenosine A3 receptors.
Mice with a targeted disruption of adenosine A(3) receptor (A(3)AR) gene were assessed for their nociceptive threshold and for their localized inflammatory response following carrageenan injected into the hindpaw. Under basal conditions no difference was seen between A(3)AR knock-out (A(3)AR(-/-)) and wild-type (A(3)AR(+/+)) mice in nociceptive response to mechanical or heat stimuli. ⋯ Thus, mice lacking A(3)AR had deficits in generating the localized inflammatory response to carrageenan, supporting a pro-inflammatory role of A(3)AR in peripheral tissues. However, no evidence for a role of A(3)AR in nociception and the antinociceptive effect of R-PIA was found.
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Effects of C-fiber activation on type I slowly adapting mechanoreceptor responses were investigated in a rat in vitro nerve-skin preparation using controlled mechanical stimuli. Two changes in behavior were evoked by antidromic C-fiber stimulation: (1). The type I response to mechanical stimuli was modulated in a graded fashion by antidromic C-fiber activation. ⋯ Immunohistochemical staining revealed both substance P- and calcitonin gene-related peptide-like immunoreactivity in small unmyelinated nerve fibers entering the touch dome. These results support the concepts that (1). the type I slowly adapting mechanoreceptor in rat receives input from nociceptive terminals within the touch dome. (2). The function of type I slowly adapting mechanoreceptors is modulated by axon reflex activation of nociceptor terminals, which may play a role in altering the type I response during states of mechanical allodynia and have paracrine and autocrine influences on maintenance of touch dome structure.
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X-linked forms of non-specific mental retardation are complex disorders, for which mutations in several genes have recently been identified. These include OPHN1, GDI1, PAK3, IL1RAPL, TM4SF2, FMR2 and RSK2. ⋯ Furthermore we observed a significant increase in mRNA levels of PAK3 and IL1RAPL following LTP induction. These results suggest a possible role for these four genes in activity-dependent brain plasticity.