Brain research
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The P300 in event-related potentials (ERPs) has been implicated in outcome evaluation and reward processing, but it is controversial as to what aspects of reward processing it is sensitive. This study manipulated orthogonally reward valence, reward magnitude, and expectancy towards reward magnitude in a monetary gambling task and observed both the valence and the magnitude effects on the P300, but only when the amount of reward was expected on the basis of a previous cue. The FRN (feedback-related negativity), defined as the mean amplitudes of ERP responses to the loss or the gain outcome in the 250-350 ms time window post-onset of feedback, was found to be sensitive not only to reward valence, but also to expectancy towards reward magnitude and reward magnitude, with the violation of expectancy and the small magnitude eliciting more negative-going FRN. These findings demonstrate that while the FRN may function as a general mechanism that evaluates whether the outcome is consistent or inconsistent with expectation, the P300 is sensitive to a later, top-down controlled process of outcome evaluation, into which factors related to the allocation of attentional resources, including reward valence, reward magnitude, and magnitude expectancy, come to play.
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General anesthetics variably enhance inhibitory synaptic transmission that relies on (-aminobutyric acid (GABA) and GABAA receptor function with distinct differences across brain regions. Activation of "extra-synaptic" GABAA receptors produces a tonic current considered the most sensitive target for general anesthetics, particularly in forebrain neurons. To evaluate the contribution of poor drug access to neurons in slices, we tested the intravenous anesthetic propofol in mechanically isolated neurons from the solitary tract nucleus (NTS). ⋯ We conclude that presynaptic actions of propofol depend on a depolarizing chloride gradient across presynaptic inhibitory terminals. Our results in isolated neurons indicate that propofol pharmacokinetics intrinsically trigger the tonic currents slowly and the time course is not related to slow permeation or delivery. Unlike forebrain, phasic NTS GABAA receptors are more sensitive to propofol than tonic receptors but that presynaptic GABAA receptor mechanisms regulate GABA release.
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Translocator protein 18 kDa (TSPO), previously known as the peripheral benzodiazepine receptor (PBR), is predominantly located in the mitochondrial outer membrane and plays an important role in steroidogenesis, immunomodulation, cell survival and proliferation. Previous studies have shown an increased expression of TSPO centrally in neuropathology, as well as in injured nerves. TSPO has also been implicated in modulation of nociception. ⋯ The TSPO agonist Ro5-4864, given intrathecally, dose-dependently retarded or prevented the development of mechanical allodynia and thermal hyperalgesia in rats with CFA-induced monoarthritis. These findings provide evidence that spinal TSPO is involved in the development and maintenance of inflammatory pain behaviors in rats. Thus, spinal TSPO may present a central target as a complementary therapy to reduce inflammatory pain.
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Angiotensin II (Ang II) receptor blockade is beneficial in stroke, possibly due to attenuation of vascular oxidative stress. Mice genetically targeted for the superoxide-forming vascular NADPH oxidase subunit, NOX1, have a blunted hypertensive response to Ang II. We therefore hypothesised that NOX1 is mechanistically involved in Ang II-induced superoxide production by cerebral arteries, and potentially in stroke outcome. ⋯ However, cortical infarct volume (which was very modest in WT) was approximately 4-fold greater in brains of NOX1-KO versus WT. Thus, NOX1 is essential for superoxide production in large cerebral arteries in response to Ang II but not under basal conditions. Furthermore, NOX1 does not appear to contribute to stroke size, and it may limit cortical infarct development following cerebral ischemia.
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The left parietal cortex contributes to goal-directed hand movement. In this study, we targeted this region with transcranial magnetic stimulation (TMS) to assess the effects on a wider distributed circuitry related to motor control. Ten healthy subjects underwent 3 Tesla functional magnetic resonance imaging (fMRI) with interleaved TMS. ⋯ Movement imagery after TMS showed significantly increased activation in the left medial prefrontal cortex, right lateral prefrontal cortex, left supramarginal gyrus and right occipital cortex, while a decrease was present in bilateral anterior parietal cortex (P<0.01 voxel-level; P<0.05 volume corrected). Activation changes after TMS of left superior parietal cortex thus appears to increase prefrontal and posterior parietal cortex activation, associated with a reduced function of the anterior parietal cortex, including S2. These changes are thought to reflect an impaired ability to estimate the proprioceptive consequences of movement during its preparation, which is compensated by the increased contribution of more remote parietal and prefrontal cortical regions.