Neuroscience
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The whole-cell patch-clamp technique was used to record current responses to AMPA, N-methyl-d-aspartate (NMDA), muscimol and dibenzoyl-ATP (Bz-ATP) in superficial (reactive/gliotic) substantia gelatinosa (SG) astrocytes and neurons of spinal cord slices kept for different periods of time in organotypic culture. Currents induced by AMPA, NMDA and muscimol confirmed the existence of their specific receptors in 2-week-old neurons; astrocytes cultured for the same period of time responded to AMPA and muscimol, but not to NMDA. AMPA had a larger effect on 2-week-old astrocytes than on the 1-week-old ones, in spite of a similar sensitivity of the age-matched neurons to this amino acid. ⋯ Neurons located in deep layers exhibited after 1week of culturing much larger Bz-ATP currents than the superficial ones of the same age. In conclusion, whereas resting astrocytes had culture period-independent P2X7 receptor-sensitivity, reactive/gliotic astrocytes exhibited P2X7 receptor-sensitivity increasing in parallel with the prolongation of the time spent in culture. The results with Bz-ATP agree with the facilitation of AMPA-induced currents in reactive astrocytes during development, and with the hypothesis that extracellular ATP is an ontogenetically early transmitter/signaling molecule in the CNS.
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Dense reciprocal connections link the rat anterior thalamic nuclei with the prelimbic, anterior cingulate and retrosplenial cortices, as well as with the subiculum and postsubiculum. The present study compared the ipsilateral thalamic-cortical connections with the corresponding crossed, contralateral connections between these same sets of regions. All efferents from the anteromedial thalamic nucleus to the cortex, as well as those to the subiculum, remained ipsilateral. ⋯ Likewise, within the hippocampus, the postsubiculum seemingly had only ipsilateral efferent and afferent connections with the anterior thalamic and laterodorsal nuclei. While the bilateral cortical projections to the anterior thalamic nuclei originated predominantly from layer VI, the accompanying sparse projections from layer V largely gave rise to ipsilateral thalamic inputs. In testing a potentially unifying principle of anterior thalamic - cortical interactions, a slightly more individual pattern emerged that reinforces other evidence of functional differences within the anterior thalamic and also helps to explain the consequences of unilateral interventions involving these nuclei.
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Several phosphorylation signaling pathways have been implicated in the pathogenesis of epilepsy arising from both genetic causes and acquired insults to the brain. Identification of dysfunctional signaling pathways in epilepsy may provide novel targets for antiepileptic therapies. We previously described a deficit in phosphorylation signaling mediated by p38 mitogen-activated protein kinase (p38 MAPK) that occurs in an animal model of temporal lobe epilepsy, and that produces neuronal hyperexcitability measured in vitro. ⋯ Administration of JNK inhibitor SP600125 significantly decreased seizure frequency in a dose-dependent manner without causing overt behavioral abnormalities. Biochemical analysis showed increased JNK expression and activity in untreated epileptic animals. These results show for the first time that JNK is hyperactivated in an animal model of epilepsy, and that phosphorylation signaling mediated by JNK may represent a novel antiepileptic target.
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Pain is processed in a large neural network that partially overlaps structures involved in emotion processing. Despite the fact that pain and emotion are known to share neural regions and interact in numerous clinical conditions, relatively little is known about the interaction of pain and emotion at the neural level. This study on healthy adults aimed to investigate the interaction between negative and positive emotional stimuli and experimental pain in an essential pain processing network. ⋯ The interaction of positive emotion and pain stimuli led to bilateral activation of the SII and left insula. These findings reveal interaction in parts of the pain processing network during simultaneous emotion and physical pain. We demonstrated a valence-independent interaction of emotion and pain in SII.