The Journal of neuroscience : the official journal of the Society for Neuroscience
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Specific missense mutations in the CACNA1A gene, which encodes a subunit of voltage-gated CaV2.1 channels, are associated with familial hemiplegic migraine type 1 (FHM1), a rare monogenic subtype of common migraine with aura. We used transgenic knock-in (KI) mice harboring the human pathogenic FHM1 mutation S218L to study presynaptic Ca(2+) currents, EPSCs, and in vivo activity at the calyx of Held synapse. ⋯ The gain-of-function of transmitter release of the S218L mutant was reproduced in vivo, including evidence for an increased release probability, demonstrating its relevance for glutamatergic transmission. This synaptic phenotype may explain the misbalance between excitation and inhibition in neuronal circuits resulting in a persistent hyperexcitability state and other migraine-relevant mechanisms such as an increased susceptibility to cortical spreading depression.
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Randomized Controlled Trial
Midline frontal cortex low-frequency activity drives subthalamic nucleus oscillations during conflict.
Making the right decision from conflicting information takes time. Recent computational, electrophysiological, and clinical studies have implicated two brain areas as being crucial in assuring sufficient time is taken for decision-making under conditions of conflict: the medial prefrontal cortex and the subthalamic nucleus (STN). Both structures exhibit an elevation of activity at low frequencies (<10 Hz) during conflict that correlates with the amount of time taken to respond. ⋯ Crucially, simultaneous midline frontal electroencephalographic recordings revealed an increase in the theta-delta band coherence between the two structures that was specific to high-conflict trials. Activity over the midline frontal cortex was Granger causal to that in STN. These results establish the cortico-subcortical circuit enabling successful choices to be made under conditions of conflict and provide support for the hypothesis that the brain uses frequency-specific channels of communication to convey behaviorally relevant information.
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γ-Hydroxybutyrate (GHB) is an approved therapeutic for the excessive sleepiness and sudden loss of muscle tone (cataplexy) characteristic of narcolepsy. The mechanism of action for these therapeutic effects is hypothesized to be GABAB receptor dependent. We evaluated the effects of chronic administration of GHB and the GABAB agonist R-baclofen (R-BAC) on arousal state and cataplexy in two models of narcolepsy: orexin/ataxin-3 (Atax) and orexin/tTA; TetO diphtheria toxin mice (DTA). ⋯ Cataplexy decreased from baseline in 57 and 86% of mice after GHB and R-BAC, respectively, whereas cataplexy increased in 79% of the mice after VEH. At the doses tested, R-BAC suppressed cataplexy to a greater extent than GHB. These results suggest utility of R-BAC-based therapeutics for narcolepsy.
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Musicians have been used extensively to study neural correlates of long-term practice, but no studies have investigated the specific effects of training musical creativity. Here, we used human functional MRI to measure brain activity during improvisation in a sample of 39 professional pianists with varying backgrounds in classical and jazz piano playing. We found total hours of improvisation experience to be negatively associated with activity in frontoparietal executive cortical areas. ⋯ These results indicate that even neural mechanisms involved in creative behaviors, which require a flexible online generation of novel and meaningful output, can be automated by training. Second, improvisational musical training can influence functional brain properties at a network level. We show that the greater functional connectivity seen in experienced improvisers may reflect a more efficient exchange of information within associative networks of importance for musical creativity.
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Locus ceruleus (LC) noradrenergic neurons are critical in generating alertness. In addition to inducing cortical arousal, the LC also orchestrates changes in accompanying autonomic system function that compliments increased attention, such as during stress, excitation, and/or exposure to averse or novel stimuli. Although the association between arousal and increased heart rate is well accepted, the neurobiological link between the LC and parasympathetic neurons that control heart rate has not been identified. ⋯ This study demonstrates LC noradrenergic neurons inhibit the brainstem CVNs that generate parasympathetic activity to the heart. This inhibition of CVNs would increase heart rate and risks associated with tachycardia. The receptors activated within this pathway, α1 and/or β1 receptors, are targets for clinically prescribed antagonists that promote slower, cardioprotective heart rates during heightened vigilant states.