Brain research
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Recently we introduced a robust measure, integrated local correlation (ILC), of local connectivity in the brain using fMRI data which reflects the temporal correlation of brain activity in every voxel neighborhood. The current work studies ILC in fMRI data obtained in the absence and presence of sevoflurane anesthesia (0%, 2%, and 1% end-tidal concentration, respectively) administered to healthy volunteers. ILC was determined specifically in regions of the default mode network (DMN) to address local changes in each state. ⋯ By contrast, ILC remained attenuated prefrontally in the 1% condition, which indicates uncoupling of the frontal areas of DMN during light anesthesia. These results confirm widespread anesthetic-induced cortical suppression but also demonstrate that the local connectivity of the prefrontal cortex is rapidly reduced by sevoflurane. It remains to be seen whether these alterations arise locally as a direct consequence of anesthetic action on local neurons or are driven by distant changes in oscillations and activity elsewhere in the brain.
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The periaqueductal gray (PAG), especially in a region between the levels the oculomotor nucleus and the trochlear nucleus, was suggested to be the essential relay center that conveys information of bladder fullness to the pontine micturition center (Barrington's nucleus). The present study examined this hypothesis by transecting the brainstem in anesthetized cats. In eight cases of the midbrain transection, all (n=3) or most (n=5) of the PAG between the levels the oculomotor nucleus and the trochlear nucleus was separated from the intact side of the brain. ⋯ In the one case that received a transection through the rostral part of Barrington's nucleus, the amplitude of the micturition contraction was 43% of that before transection. This study demonstrates that Barrington's nucleus is essential, but the PAG is not essential, for evoking micturition. Our results suggest that the information of bladder fullness in the cat is conveyed to Barrington's nucleus either directly from the lumbosacral neurons or indirectly via relay neurons located below the midbrain.
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Descending noradrenergic inhibition is an important endogenous pain-relief mechanism which can be activated by local glutamate signaling. In the present study, we examined the effect of glutamate transporter activation by riluzole in the regulation of activity of locus coeruleus (LC) neurons, which provide the major inhibitory descending noradrenergic projection to the spinal cord. Local injection of riluzole into the LC dose-dependently reduced hypersensitivity in rats after L5-L6 spinal nerve ligation (SNL). ⋯ This riluzole-induced pCREB activation in LC neurons was also blocked by CNQX and CBX. In the primary astrocyte culture, riluzole enhanced glutamate-induced glutamate release. Contrary to expectations, these results suggest that activation of glutamate transporters in the LC results in increase of extracellular glutamate signaling, possibly via facilitation of glutamate release from astrocytes, and activation of LC neurons to induce descending inhibition, and that this paradoxical action of glutamate transporters in the LC requires gap-junction connections.
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Astrocytes are responsible for the majority of the clearance of extracellular glutamate released during neuronal activity. dl-threo-beta-benzyloxyaspartate (TBOA) is extensively used as inhibitor of glutamate transport activity, but suffers from relatively low affinity for the transporter. Here, we characterized the effects of (2S, 3S)-3-[3-[4-(trifluoromethyl)benzoylamino]benzyloxy]aspartate (TFB-TBOA), a recently developed inhibitor of the glutamate transporter on mouse cortical astrocytes in primary culture. The glial Na(+)-glutamate transport system is very efficient and its activation by glutamate causes rapid intracellular Na(+) concentration (Na(+)(i)) changes that enable real time monitoring of transporter activity. ⋯ TFB-TBOA also efficiently inhibited Na(+)(i) elevations caused by the application of d-aspartate, a transporter substrate that does not activate non-NMDA ionotropic receptors. TFB-TBOA was found not to influence the membrane properties of cultured cortical neurons recorded in whole-cell patch clamp. Thus, TFB-TBOA, with its high potency and its apparent lack of neuronal effects, appears to be one of the most useful pharmacological tools available so far for studying glial glutamate transporters.
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Over the past two decades single cell recordings in primates and neuroimaging experiments in humans have uncovered the key properties of visuo-motor mirror neurons located in monkey premotor cortex and parietal cortices as well as homologous areas in the human inferior frontal and inferior parietal cortices which presumably house neurons with similar response properties. One of the most interesting claims regarding the human mirror neuron system (MNS) is that its activity reflects high-level action understanding. If this was the case, one would expect signal in the MNS to differentiate between meaningful and meaningless actions. ⋯ Consistent with the notion that the MNS represents high-level action understanding, meaningful and meaningless actions elicited BOLD signal differences at bilateral sites in the supramarginal gyrus (SMG) of the inferior parietal lobule (IPL) where we observed a double dissociation between BOLD response and meaningfullness of actions. Comparison of superadditive responses in the inferior frontal gyrus (IFG) and IPL (supramarginal) regions revealed differential contributions to action understanding. These data further specify the role of specific components of the MNS in understanding object-directed actions.