The Journal of neuroscience : the official journal of the Society for Neuroscience
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Within neurons, mitochondria are nonuniformly distributed and are retained at sites of high activity and metabolic demand. Glutamate transport and the concomitant activation of the Na(+)/K(+)-ATPase represent a substantial energetic demand on astrocytes. We hypothesized that mitochondrial mobility within astrocytic processes might be regulated by neuronal activity and glutamate transport. ⋯ Inhibition of reversed Na(+)/Ca(2+) exchange also increased the percentage of mitochondria that were mobile. Last, we demonstrated that neuronal activity increases the probability that mitochondria appose GLT-1 particles within astrocyte processes, without changing the proximity of GLT-1 particles to VGLUT1. These results imply that neuronal activity and the resulting clearance of glutamate by astrocytes regulate the movement of astrocytic mitochondria and suggest a mechanism by which glutamate transporters might retain mitochondria at sites of glutamate uptake.
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In the current study we sought to dissociate the component processes of working memory (WM) (vigilance, encoding and maintenance) that may be differentially impaired in attention-deficit/ hyperactivity disorder (ADHD). We collected electroencephalographic (EEG) data from 52 children with ADHD and 47 typically developing (TD) children, ages 7-14 years, while they performed a spatial Sternberg working memory task. We used independent component analysis and time-frequency analysis to identify midoccipital alpha (8-12 Hz) to evaluate encoding processes and frontal midline theta (4-7 Hz) to evaluate maintenance processes. ⋯ Last, subjects with ADHD showed age-independent attenuation of evoked responses to warning cues, suggesting low vigilance. Combined, these three EEG measures predicted diagnosis with 70% accuracy. We conclude that the interplay of impaired vigilance and encoding in ADHD may compromise maintenance and lead to impaired WM performance in this group.
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Can monkeys learn simple auditory sequences and detect when a new sequence deviates from the stored pattern? Here we tested the predictive-coding hypothesis, which postulates that cortical areas encode internal models of sensory sequences at multiple hierarchical levels, and use these predictive models to detect deviant stimuli. In humans, hierarchical predictive coding has been supported by studies of auditory sequence processing, but it is unclear whether internal hierarchical models of auditory sequences are also available to nonhuman animals. ⋯ We observed distinct fMRI responses to first-order violations in auditory cortex and to second-order violations in a frontoparietal network, a distinction only demonstrated in conscious humans so far. The results indicate that the capacity to represent and predict the structure of auditory sequences is shared by humans and nonhuman primates.
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The electrogenic sodium bicarbonate cotransporter NBCe1 (SLC4A4) is a robust regulator of intracellular H(+) and a significant base carrier in many cell types. Using wild-type (WT) and NBCe1-deficient (NBC-KO) mice, we have studied the role of NBCe1 in cortical astrocytes in culture and in situ by monitoring intracellular H(+) using the H(+)-sensitive dye BCECF [2',7'-bis-(carboxyethyl)-5-(and-6)-carboxyfluorescein] in wide-field and confocal microscopy. ⋯ Human NBCe1 heterologously expressed in Xenopus oocytes could be activated by adding 1-3 mm HCO3(-), and even by residual HCO3(-) in a nominally CO2/HCO3(-)-free saline solution. Our results demonstrate a surprisingly high apparent bicarbonate sensitivity mediated by NBCe1 in cortical astrocytes, suggesting that NBCe1 may operate over a wide bicarbonate concentration in these cells.
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Ongoing/spontaneous pain behavior is associated with ongoing/spontaneous firing (SF) in adult DRG C-fiber nociceptors (Djouhri et al., 2006). Causes of this SF are not understood. We show here that conducting (sometimes called uninjured) C-nociceptors in neuropathic pain models with more hyperpolarized resting membrane potentials (Ems) have lower SF rates. ⋯ After CFA-induced inflammation, spontaneous foot lifting (a measure of spontaneous pain) was (1) greater in rats with naturally lower TREK2 in ipsilateral small DRG neurons and (2) increased by siRNA-induced TREK2 knockdown in vivo. We conclude that TREK2 hyperpolarizes IB4 binding C-nociceptors and limits pathological spontaneous pain. Similar TREK2 distributions in small DRG neurons of several species suggest that these role(s) of TREK2 may be widespread.