4 research outputs found
Ethanol modulation of mammalian BK channels in excitable tissues: molecular targets and their possible contribution to alcohol-induced altered behavior
No full textIn most tissues, the function of calcium- and voltage-gated potassium (BK) channels is modified in response to ethanol concentrations reached in human blood during alcohol intoxication. In general, modification of BK current from ethanol-naïve preparations in response to brief ethanol exposure results from changes in channel open probability without modification of unitary conductance or change in BK protein levels in the membrane. Protracted and/or repeated ethanol exposure, however, may evoke changes in BK expression. The final ethanol effect on BK open probability leading to either BK current potentiation or BK current reduction is determined by an orchestration of molecular factors, including levels of activating ligand (cytosolic calcium), BK subunit composition and posttranslational modifications, and the channel’s lipid microenvironment. These factors seem to allosterically regulate a direct interaction between ethanol and a recognition pocket of discrete dimensions recently mapped to the channel-forming (slo1) subunit. Type of ethanol exposure also plays a role in the final BK response to the drug: in several central nervous system regions (e.g., striatum, primary sensory neurons, and supraoptic nucleus), acute exposure to ethanol reduces neuronal excitability by enhancing BK activity. In contrast, protracted or repetitive ethanol administration may alter BK subunit composition and membrane expression, rendering the BK complex insensitive to further ethanol exposure. In neurohypophysial axon terminals, ethanol potentiation of BK channel activity leads to a reduction in neuropeptide release. In vascular smooth muscle, however, ethanol inhibition of BK current leads to cell contraction and vascular constriction
The amygdala’s response to face and emotional information and potential category-specific modulation of temporal cortex as a function of emotion.
No full textThe amygdala has been implicated in the processing of emotion and animacy information and to be responsivity to novelty. However, the way in which these functions interact is poorly understood. Subjects (N= 30) viewed threatening or neutral images that could be either animate (facial expressions) or inanimate (objects) in the context of a dot probe task. The amygdala showed responses to both emotional and animacy information, but no emotion by stimulus-type interaction; i.e., emotional face and object stimuli, when matched for arousal and valence, generate comparable amygdala activity relative to neutral face and object stimuli. Additionally, a habituation effect was not seen in amygdala; however, increased amygdala activity was observed for incongruent relative to congruent negative trials in second vs. first exposures. Furthermore, medial fusiform gyrus showed increased response to inanimate stimuli, while superior temporal sulcus showed increased response to animate stimuli. Greater functional connectivity between bilateral amygdala and medial fusiform gyrus was observed to negative vs. neutral objects, but to fearful vs. neutral faces. The current data suggest that the amygdala is responsive to animate and emotional stimuli. Additionally, these data suggest that the interaction between the various functions of the amygdala may need to be considered simultaneously to fully understand how they interact. Moreover, they suggest category-specific modulation of medial fusiform cortex as a function of emotion
Age-related Changes In Sleep Spindles Characteristics During Daytime Recovery Following a 25-Hour Sleep Deprivation
No full textObjectives: The mechanisms underlying sleep spindles (~11-15Hz; >0.5s) help to protect sleep. With age, it becomes increasingly difficult to maintain sleep at a challenging time (e.g. daytime), even after sleep loss. This study compared spindle characteristics during daytime recovery and nocturnal sleep in young and middle-aged adults. In addition, we explored whether spindles characteristics in baseline nocturnal sleep were associated with the ability to maintain sleep during daytime recovery periods in both age groups.Methods: Twenty-nine young (15 women and 14 men; 27.3 ± 5.0) and 31 middle-aged (19 women and 13 men; 51.6 y ± 5.1) healthy subjects participated in a baseline nocturnal sleep and a daytime recovery sleep after 25 hours of sleep deprivation. Spindles were detected on artefact-free NREM sleep epochs. Spindle density (nb/min), amplitude (μV), frequency (Hz) and duration (s) were analyzed on parasagittal (linked-ears) derivations. Results: In young subjects, spindle frequency increased during daytime recovery sleep as compared to baseline nocturnal sleep in all derivations, whereas middle-aged subjects showed spindle frequency enhancement only in the prefrontal derivation. No other significant interaction between age group and sleep condition was observed. Spindle density for all derivations and centro-occipital spindle amplitude decreased whereas prefrontal spindle amplitude increased from baseline to daytime recovery sleep in both age groups. Finally, no significant correlation was found between spindle characteristics during baseline nocturnal sleep and the marked reduction in sleep efficiency during daytime recovery sleep in both young and middle-aged subjects.Conclusion: These results suggest that the interaction between homeostatic and circadian pressure module spindle frequency differently in aging. Spindle characteristics do not seem to be linked with the ability to maintain daytime recovery sleep
The perils of global signal regression for group comparisons: A case study of Autism Spectrum Disorders
No full textWe have previously argued from a theoretical basis that the standard practice of regression of the Global Signal from the FMRI time series in functional connectivity studies is ill advised, particularly when comparing groups of participants. Here, we demonstrate in resting-state data from participants with an Autism Spectrum Disorder and matched controls that these concerns are also well founded in real data. Using the prior theoretical work to formulate predictions, we show: 1) rather than simply altering the mean or range of correlation values amongst pairs of brain regions, Global Signal Regression systematically alters the rank ordering of values in addition to introducing negative values, 2) it leads to a reversal in the direction of group correlation differences relative to other preprocessing approaches, with a higher incidence of both long-range and local correlation differences that favor the Autism Spectrum Disorder group, 3) the strongest group differences under other preprocessing approaches are the ones most altered by Global Signal Regression, and 4) locations showing group differences no longer agree with those showing correlations with behavioral symptoms within the Autism Spectrum Disorder group. The correlation matrices of both participant groups under Global Signal Regression were well predicted by our previous mathematical analyses, demonstrating that there is nothing mysterious about these results. Finally, when independent physiological nuisance measures are lacking, we provide a simple alternative approach for assessing and lessening the influence of global correlations on group comparisons that replicates our previous findings. While this alternative performs less well for symptom correlations than our favored preprocessing approach that includes removal of independent physiological measures, it is preferable to the use of Global Signal Regression, which prevents unequivocal conclusions about the direction or location of group differences
