Neuroscience
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Focal malformations of cortical development (FMCD) are highly associated with several neurological disorders including intractable epilepsy and neurocognitive disabilities. Over the past decade, several FMCD subtypes have been linked to hyperactivation of the mammalian target of rapamycin (mTOR) signaling cascade. ⋯ These mechanisms have been directly linked to mTOR activation. Perhaps most compelling, pharmacological inhibition of mTOR has been implemented successfully in clinical trials for select FMCD and provides a new vista for treatment.
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Alpha7 nicotinic acetylcholine receptors (α7nAChRs) mediate nicotine-induced burst-firing of dopamine neurons in the ventral tegmental area (VTA), a limbic brain region critically involved in reward and in dopamine D2 receptor (D2R)-related cortical dysfunctions associated with psychosis. The known presence of α7nAChRs and Gi-coupled D2Rs in dopamine neurons of the VTA suggests that these receptors are targeted to at least some of the same neurons in this brain region. To test this hypothesis, we used electron microscopic immunolabeling of antisera against peptide sequences of α7nACh and D2 receptors in the mouse VTA. ⋯ Of 160 D2R-labeled terminals, 81.2% were presynaptic to dendrites that expressed α7nAChR alone or together with the D2R. Numerous glial processes inclusive of those enveloping either excitatory- or inhibitory-type synapses also contained single labeling for D2R (n=152) and α7nAChR (n=561). These results suggest that classic antipsychotic drugs, all of which block the D2R, may facilitate α7nAChR-mediated burst-firing by elimination of D2R-dependent inhibition in neurons expressing both receptors as well as by indirect pre-synaptic and glial mechanisms.
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Early blindness results in occipital cortex neurons responding to a wide range of auditory and tactile stimuli. These changes in tuning properties are accompanied by an extensive reorganization of the occipital cortex that includes alterations in anatomical structure, neurochemical and metabolic pathways. ⋯ Here, using (1)H magnetic resonance spectroscopy in nine early blind and normally sighted subjects, we find that early blindness is associated with higher levels of creatine, choline and myo-Inositol and indications of lower levels of GABA within the occipital cortex. These results suggest that the cross-modal responses associated with early blindness may, at least in part, be driven by changes within occipital biochemical pathways.
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The voluntary control of respiration is used as a common means to regulate pain and emotions and is fundamental to various relaxation and meditation techniques. The aim of the present study was to examine how breathing frequency and phase affect pain perception, spinal nociceptive activity (RIII-reflex) and brain activity (scalp somatosensory-evoked potentials - SEP's). In 20 healthy volunteers, painful electric shocks individually adjusted to 120% of the RIII-reflex threshold were delivered to the sural nerve near the end of inspiration or expiration phases, during three cued-breathing conditions: (1) slow breathing (0.1 Hz) with slow (4s) inspiration (0.1Hz-SlowIns), (2) slow breathing (0.1 Hz) with fast (2s) inspiration (0.1 Hz-FastIns), and (3) normal breathing (0.2 Hz) with fast (2s) inspiration (0.2 Hz). ⋯ Slow breathing also increased the amplitude of respiratory sinus arrhythmia (RSA), although these changes were not significantly associated with changes in pain responses. In conclusion, this study shows that pain and pain-related brain activity may be reduced during inspiration but these changes are dissociated from spinal nociceptive transmission. The small amplitude of these effects suggests that factors other than respiration contribute to the analgesic effects of relaxation and meditation techniques.
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Striatal dopaminergic denervation leads to a change in afferent activity within the basal ganglia. Coupled with the effect of local dopaminergic denervation in the subthalamic nucleus, this is likely to affect the responsiveness of subthalamic neurons to their hyperdirect inputs in Parkinson's disease. Therefore, in this report, we investigated subthalamic nucleus responses to visual stimuli relayed by one such input - the superior colliculus - in 6-hydroxydopamine (6-OHDA)-lesioned rats. ⋯ A classic hypothesis in Parkinson's disease suggests that following dopaminergic denervation, the discharge of cells in the substantia nigra pars reticulata increases, thereby intensifying the inhibitory influence that this structure exerts on its targets in the thalamus and brainstem. Our results suggest that neuroadaptations may have taken place within the superior colliculus in order to maintain normal function in the face of increased inhibitory tone coming from the substantia nigra pars reticulata, which once reduced, gave rise to facilitated responding. This facilitated responding in the superior colliculus then appears to lead to facilitated responding in the subthalamic nucleus.