Neuroscience
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Since 1967, spinal cord stimulation (SCS) has been used to manage chronic intractable pain of the trunk and limbs. Compared to traditional high-intensity, low-frequency (<100 Hz) SCS that is thought to produce paresthesia and pain relief by stimulating large myelinated fibers in the dorsal column (DC), low-intensity, high-frequency (10 kHz) SCS has demonstrated long-term pain relief without generation of paresthesia. ⋯ By using in vivo and ex vivo electrophysiological approaches, we found that low-intensity (sub-sensory threshold) 10 kHz SCS, but not 1 kHz or 5 kHz SCS, selectively activates inhibitory interneurons in the spinal DH. This study suggests that low-intensity 10 kHz SCS may inhibit pain sensory processing in the spinal DH by activating inhibitory interneurons without activating DC fibers, resulting in paresthesia-free pain relief.
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Visceral pain originating from chronic inflammation of the pancreas is often intractable and difficult to manage clinically. However, the pathogenesis of the central nervous system underlying visceral pain is still poorly understood. The aim of the present study was to investigate the role of the midbrain ventrolateral periaqueductal gray (vlPAG) in a rat model of chronic visceral pain induced by pancreatitis. ⋯ Furthermore, intra-vlPAG microinjection of AMPA alleviated DBTC-induced abdominal hypersensitivity. Taken together, our findings suggest that diminished glutamatergic synaptic strength via both presynaptic and postsynaptic mechanisms in the midbrain vlPAG is associated with DBTC-induced abdominal hypersensitivity. In addition, activation of AMPA receptors in the vlPAG alleviates DBTC-induced abdominal hypersensitivity.
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Mechanisms of Impulsive Responding to Temporally Predictable Events as Revealed by Electromyography.
Temporal predictability optimises behaviour when a simple response is required, as demonstrated by faster reaction times (RTs) and higher accuracy. However, its beneficial effects come at a cost under situations of response conflict. Here, we investigated the motor underpinnings of behaviour to temporally predictable events in the Simon conflict task. ⋯ There was, however, no effect of temporal predictability on subsequent suppression of partial errors. Our results provide direct evidence that temporal predictability acts by increasing the urge to initiate a fast, yet potentially erroneous, response. This mechanism parsimoniously explains both beneficial effects of temporal predictability when no conflict in the environment is present, as well as its costs when more complex motor behaviour is required.
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Kainate receptors (KARs) are glutamate receptors with ionotropic and metabotropic activity composed of the GluK1-GluK5 subunits. We previously reported that KARs modulate excitatory and inhibitory transmission in the olfactory bulb (OB). Zinc, which is highly concentrated in the OB, also appears to modulate OB synaptic transmission via actions at other ionotropic glutamate receptors (i.e., AMPA, NMDA). ⋯ It is also of potential importance given our previously reported molecular data suggesting that OB neurons express relatively high levels of GluK1 and GluK2. Our present findings suggest that a physiologically relevant concentration of zinc modulates KARs expressed by M/T cells. As M/T cells are targets of zinc-containing olfactory sensory neurons, synaptically released zinc may influence odor information-encoding synaptic circuits in the OB via actions at KARs.
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Circular RNAs are an increasingly important topic in non-coding RNA biology, drawing considerable attention in recent years. Accumulating evidence suggests a critical role for circular RNAs in both early and latent stages of disease pathogenesis. ⋯ Disruption of these processes, including those seen in response to brain injury, can have serious consequences such as hemiplegia, aphasia, coma, and death. In this review, we describe the role of circular RNAs in the context of brain injury and explore the potential connection between circular RNAs, brain hypoxic ischemic injury, ischemia-reperfusion injury, and traumatic injury.