The Journal of neuroscience : the official journal of the Society for Neuroscience
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Astrocytes are now distinguished as major regulators of neuronal growth and synaptic development. Recently, they have been identified as key players in the progression of a number of developmental disorders; however, in fragile X syndrome (FXS), the role of astrocytes is not known. ⋯ These experiments are the first to establish a role for astrocytes in the altered neurobiology of FXS. Our results support the notion that astrocytes contribute to abnormal dendrite morphology and the dysregulated synapse development in FXS.
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Opioids remain the mainstay of treatment for severe pain, but the associated hyperalgesia and tolerance are significant impediments to achieving adequate pain relief with opioids. Here we show that in the spinal cord, brief application of the mu-opioid receptor agonist (D-Ala(2),N-Me-Phe(4),Gly-ol(5))-enkephalin (DAMGO) at 1 mum, but not at 1-10 nm, caused an initial decrease followed by a large and long-lasting increase in the amplitude of monosynaptic EPSCs evoked from the dorsal root in approximately 50% of lamina I and II neurons. However, postsynaptic dialysis of the G-protein inhibitor had no effect on DAMGO-induced initial inhibition and long-term potentiation (LTP) in either lamina I or II neurons. ⋯ Strikingly, ablation of TRPV1-expressing primary afferents not only eliminated DAMGO-induced LTP but also prolonged DAMGO-induced inhibition of the miniature and evoked EPSCs (i.e., long-term depression). Thus, our study strongly suggests that TRPV1-expressing primary afferents play a prominent role in opioid-induced presynaptic LTP, which challenges a previous report suggesting the postsynaptic nature of this opioid-induced LTP. This excitatory effect of opioids on primary afferents can counteract the inhibitory effect of opioids on synaptic transmission at the spinal level and is likely involved in opioid-induced hyperalgesia and tolerance.
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Apoptosis of neurons in the maturing neocortex has been recorded in a wide variety of mammals, but very little is known about its effects on cortical differentiation. Recent research has implicated the RhoA GTPase subfamily in the control of apoptosis in the developing nervous system and in other tissue types. Rho GTPases are important components of the signaling pathways linking extracellular signals to the cytoskeleton. ⋯ This was not explained by a change in the migration of neurons during the formation of cortical layers but rather by a large decrease in the amount of neuronal apoptosis at postnatal day 5, the developmental maximum of cortical apoptosis. In addition, overexpression of RhoA in cortical neurons was seen to cause high levels of apoptosis. These results demonstrate that RhoA-subfamily members play a major role in developmental apoptosis in postnatal neocortex of the mouse but that decreased apoptosis does not alter cortical cytoarchitecture and patterning.
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Comparative Study
Autofluorescent flavoprotein imaging of spinal nociceptive activity.
Pain arises from activation of peripheral nociceptors, and strong noxious stimuli may cause an increase in spinal excitability called central sensitization, which is likely involved in many pathological pain states. So far, it has not been achieved to simultaneously visualize in vivo both the temporal and spatial aspects of spinal activity, including central sensitization. Using autofluorescent flavoprotein imaging (AFI), an optical technique suitable for mapping activity in nervous tissue, we demonstrate a close temporal and spatial correlation of electrically evoked nociceptive input with the spinal AFI signal, representing spinal neuronal activity. ⋯ Furthermore, we found that the AFI signal was much larger in intensity and size when the same electrical stimulation was applied after the induction of central sensitization by a subcutaneous capsaicin injection. Finally, innocuous palpation of the hindpaw did not evoke an AFI response in naive animals, but after capsaicin injection a strong response was obtained. This is the first report demonstrating simultaneously the temporal and spatial propagation of spinal nociceptive activity in vivo.
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Comparative Study
Recovery of sensorimotor function after experimental stroke correlates with restoration of resting-state interhemispheric functional connectivity.
Despite the success of functional imaging to map changes in brain activation patterns after stroke, spatiotemporal dynamics of cerebral reorganization in correlation with behavioral recovery remain incompletely characterized. Here, we applied resting-state functional magnetic resonance imaging (rs-fMRI) together with behavioral testing to longitudinally assess functional connectivity within neuronal networks, in relation to changes in associated function after unilateral stroke in rats. Our specific goals were (1) to identify temporal alterations in functional connectivity within the bilateral cortical sensorimotor system and (2) to elucidate the relationship between those alterations and changes in sensorimotor function. ⋯ Intrahemispheric functional connectivity between primary somatosensory and motor cortex areas was preserved in the lesion border zone and moderately enhanced contralesionally. The temporal pattern of changes in functional connectivity between bilateral primary motor and somatosensory cortices correlated significantly with the evolution of sensorimotor function scores. Our study (1) demonstrates that poststroke loss and recovery of sensorimotor function is associated with acute deterioration and subsequent retrieval of interhemispheric functional connectivity within the sensorimotor system and (2) underscores the potential of rs-fMRI to assess spatiotemporal characteristics of functional brain reorganization that may underlie behavioral recovery after brain injury.