Neuroscience
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Ingestion of monosodium glutamate (MSG) has been shown to cause headaches in healthy individuals and trigger migraine-like headaches in migraine sufferers. We combined immunohistochemistry, in vivo electrophysiology, and laser Doppler recordings of dural vasculature to investigate the effect of systemic administration of MSG on the trigeminovascular pathway. Immunohistochemical analysis confirmed the expression of NMDA receptors on nerve fibers innervating dural blood vessels and excitatory amino acid transporter 2 on dural blood vessels. ⋯ Systemic administration of MSG induced a 24.5% and 20.6% increase in dural flux in male and female rats, respectively. These results suggest that MSG-induced headache is mediated by the activation of peripheral NMDA receptors and subsequent dural vasodilation. Peripheral NMDA receptors are a potential target for the development of new drugs to treat headaches.
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The mammalian brain is specialized to acquire information about environmental predictors of biologically significant events. However, environments contain an array of stimuli from which animals must ascertain which ones are meaningful in the current situation. This kind of uncertainty is inherent in the discriminative fear conditioning to context task (DFCTC) during which rats are trained to associate one context with foot-shock and another distinct context with no event. ⋯ We found that inactivation of the OPFC prior to assessment measures resulted in generalized responses on the appetitive and aversive task, however, these effects may be more prominent during the aversive task. Despite generalization during activity testing, rats were able to discriminate between the two contexts during preference. These results point to a broader role for the OPFC constraining responses to perfect predictors of biologically significant events in uncertain contexts.
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Females are more likely to experience visceral pain than males, yet mechanisms underlying this sex bias are not fully elucidated. Moreover, pain sensitivity can change throughout the menstrual cycle. Alterations in the glutamatergic system have been implicated in several pain-disorders; however, whether these are sex-dependent is unclear. ⋯ Interestingly, EAAT1 mRNA expression was lower in high-estrogen and high-ERα states compared to diestrus in females. We conclude that the Spinal EAAT activity in females is different to that in males, and varies across the estrous cycle. Furthermore, the expression levels of estrogen receptors also showed a cycle-dependent pattern that may affect EAATs function and expression.
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The p21-activated kinases (PAKs) of group I are the main effectors for the small Rho GTPases, critically involved in neurodevelopment, plasticity and maturation of the nervous system. Moreover, the neuronal complexity controlled by PAK1/PAK3 signaling determines the postnatal brain size and synaptic properties. Stress induces alterations at the level of structural and functional synaptic plasticity accompanied by reductions in size and activity of the hippocampus and the prefrontal cortex (PFC). ⋯ No differences were observed for the ubiquitously expressed PAK2. Following analysis of gene coexpression demonstrated disruption of coordinated gene expression in the brain of subjects with depression. Abnormalities in mRNA expression of PAK1 and PAK3 as well as their altered coexpression patterns were detected in the brain of subjects with depression.
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Knowledge of the properties that govern the effectiveness of transcranial magnetic stimulation (TMS) interventions is critical to clinical application. Extrapolation to clinical populations has been limited by high inter-subject variability and a focus on intrinsic muscles of the hand in healthy populations. Therefore, the current study assessed variability of continuous theta burst stimulation (cTBS), a patterned TMS protocol, across an agonist-antagonist pair of extrinsic muscles of the hand. ⋯ Contraction alone had no effect confirming the effect of cTBS-Contract was driven by the interaction between neuromuscular activity and cTBS. Interactions across muscle representations should be taken into account when predicting cTBS outcomes in healthy and clinical populations. Contraction during cTBS may be a useful means of focusing aftereffects when differences in baseline excitability across overlapping agonist-antagonist cortical representations may mitigate the inhibitory effect of cTBS.