Neuroscience
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Chemokine signaling has been implicated in the pathogenesis of diabetic neuropathy; however, the role of chemokine CC motif receptor 4 (CCR4) remains unknown. The goal was to examine the function of CCR4 in hypersensitivity development and opioid effectiveness in diabetic neuropathy. Streptozotocin (STZ; 200 mg/kg, intraperitoneally administered)-induced mouse model of diabetic neuropathy were used. ⋯ Importantly, our results provide the first evidence that in a mouse model of diabetic neuropathy, single intrathecal and intraperitoneal injections of C021 diminished neuropathic pain-related behavior in a dose-dependent manner and improved motor functions. Moreover, both single intrathecal and intraperitoneal injections of C021 enhanced morphine and buprenorphine effectiveness. These results reveal that pharmacological modulation of CCR4 may be a good potential therapeutic target for the treatment of diabetic neuropathy and may enhance the effectiveness of opioids.
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The allocation of attention to specific target stimuli is key to pursue a task successfully and attain a goal in an environment that is full of distractions and competing stimuli. Area 8A in the caudal dorsolateral prefrontal cortex is considered a central area for the top-down control of attention and lesion studies in both human and non-human primates have demonstrated that this area is critical for the successful selection of targets according to internal rules. ⋯ Both parts of area 8A share connections with the parietal multimodal higher order spatial processing region. The present functional neuroimaging study demonstrates that (a) frontal area 8A is critical for the rule-based attentional selection between alternative stimuli that face the individual and (b) that there is a functional dissociation between dorsal area 8A involved in the attentional selection of auditory stimuli and ventral area 8A in the selection of visual stimuli.
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Schizophrenia in humans typically develops during and after adolescence; however, the biological underpinning for the specificity of this onset time window remains to be determined. In the present study, we investigated this knowledge gap using our own animal model for schizophrenia. Rodents and monkeys challenged with a cytokine, epidermal growth factor (EGF), as neonates are known to exhibit various behavioral and cognitive abnormalities at the post-pubertal stage. ⋯ The increase in burst firing was accompanied by a decline in Ca2+-activated K+ (ISK) currents, which influence the firing pattern of dopamine neurons. In vivo local application of the SK channel blocker apamin (80 μM) to the substantia nigra was less effective at increasing burst firing in the EGF model than in control mice, suggesting the pathologic role of the ISK decrease in this model. Thus, these results suggest that the aberrant post-pubertal hyperactivity of midbrain dopaminergic neurons is associated with the temporal specificity of the behavioral deficit of this model, and support the hypothesis that this dopaminergic aberration could be implicated in the adolescent onset of schizophrenia.
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The transition of neuronal burst firing from the interictal to ictal state contributes to seizure initiation in human temporal lobe epilepsy. The low-Mg2+ model of seizure is characterized by initial spontaneous interictal bursting events, which later developed into ictaform discharges. Both experimental and clinical studies point to a complex link between spreading depolarization (SD) and epileptiform field potentials (EFP), including SD-induced epileptic seizures. ⋯ In addition, SD significantly accelerated the transition from interictal to ictal state compared to the control tissues. Ictal activities after induction of SD exhibited a significantly longer duration. This study revealed that SD accelerates interictal-to-ictal transitions and facilitates development of ictaform discharges, possibly via the enhancement of neural synchronization, and points to the potential role of SD in seizure initiation.
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In contrast to other rhythmic tasks such as running, the preferred movement rate in cycling does not minimize energy consumption. It is possible that neurophysiological mechanisms contribute to the choice of cadence, however this phenomenon is not well understood. Eleven participants cycled at a fixed workload of 125 W and different cadences including a freely chosen cadence (FCC, ∼72), and fixed cadences of 70, 80, 90 and 100 revolutions per minute (rpm) during which transcranial magnetic stimulation (TMS) was used to measure short interval intracortical inhibition (SICI) and intracortical facilitation (ICF). ⋯ Inhibition-excitation ratio (SICI divided by ICF) declined (P = 0.014) with an increase in cadence. The results demonstrate that SICI is attenuated during FCC compared to fixed cadences. The outcomes suggest that the attenuation of intracortical inhibition and augmentation of ICF may be a contributing factor for FCC.