Neuron
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Paroxysmal extreme pain disorder (PEPD), previously known as familial rectal pain (FRP, or OMIM 167400), is an inherited condition characterized by paroxysms of rectal, ocular, or submandibular pain with flushing. A genome-wide linkage search followed by mutational analysis of the candidate gene SCN9A, which encodes hNa(v)1.7, identified eight missense mutations in 11 families and 2 sporadic cases. ⋯ Carbamazepine, a drug that is effective in PEPD, but not PE, showed selective block of persistent current associated with PEPD mutants, but did not affect the negative activation threshold of a PE mutant. PEPD and PE are allelic variants with distinct underlying biophysical mechanisms and represent a separate class of peripheral neuronal sodium channelopathy.
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Paroxysmal extreme pain disorder (PEPD), previously known as familial rectal pain (FRP, OMIM 167400), is an inherited disease causing intense burning rectal, ocular, and submandibular pain and flushing. Fertleman et al. (this issue of Neuron) show that mutations in SCN9A, the gene encoding the sodium channel Na(V)1.7 channels, are responsible for this syndrome. Together with earlier work implicating a distinct class of functional mutations in SCN9A in a distinct inherited pain syndrome, these results point to Na(V)1.7 channels as key players in signaling nociceptive information and as a potential target for drug therapy of chronic pain.
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Experience-dependent plasticity is a prominent feature of the mammalian visual cortex. Although such neural changes are most evident during development, adult cortical circuits can be modified by a variety of manipulations, such as perceptual learning and visual deprivation. ⋯ These range from shifts in the molecular profiles of cortical neurons to changes in the spatiotemporal dynamics of network activity. In this review, we will discuss recent progress and remaining challenges in understanding adult visual plasticity, focusing on the primary visual cortex.
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Dopaminergic dysregulation can cause motor dysfunction, but the mechanisms underlying dopamine-related motor disorders remain under debate. We used an inducible and reversible pharmacogenetic approach in dopamine transporter knockout mice to investigate the simultaneous activity of neuronal ensembles in the dorsolateral striatum and primary motor cortex during hyperdopaminergia ( approximately 500% of controls) with hyperkinesia, and after rapid and profound dopamine depletion (<0.2%) with akinesia in the same animal. ⋯ During hyperkinesia, corticostriatal activity became largely asynchronous, while during dopamine-depletion the synchronicity increased. Thus, dopamine-related disorders like Parkinson's disease may not stem from changes in the overall levels of cortical activity, but from dysfunctional activity coordination in corticostriatal circuits.
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Review
Neural synchrony in brain disorders: relevance for cognitive dysfunctions and pathophysiology.
Following the discovery of context-dependent synchronization of oscillatory neuronal responses in the visual system, novel methods of time series analysis have been developed for the examination of task- and performance-related oscillatory activity and its synchronization. Studies employing these advanced techniques revealed that synchronization of oscillatory responses in the beta- and gamma-band is involved in a variety of cognitive functions, such as perceptual grouping, attention-dependent stimulus selection, routing of signals across distributed cortical networks, sensory-motor integration, working memory, and perceptual awareness. ⋯ The data suggest close correlations between abnormalities in neuronal synchronization and cognitive dysfunctions, emphasizing the importance of temporal coordination. Thus, focused search for abnormalities in temporal patterning may be of considerable clinical relevance.