Neuroscience
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There is considerable interest in pre-trauma individual differences that may contribute to increased risk for developing post-traumatic stress disorder (PTSD). Identification of underlying vulnerability factors that predict differential responses to traumatic experiences is important. Recently, the relevance of homeostatic perturbations in shaping long-term behavior has been recognized. ⋯ Persistent neuronal activation marker ΔFosB immunostaining revealed altered regional neuronal activation within the hippocampus, amygdala and medial pre-frontal cortex that correlated with conditioned fear and extinction. Inter-regional co-activation mapping revealed disruptions in the coordinated activity of hippocampal dentate-amygdala-infralimbic regions and infralimbic-prelimbic associations in CO2-H mice that may explain their enhanced fear phenotype. In conclusion, our data support an association of behavioral sensitivity to interoceptive threats such as CO2 with altered fear responding to exteroceptive threats and suggest that "CO2-sensitive" individuals may be susceptible to developing PTSD.
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Repeated induction of a temporary threshold shift (TTS) may result in a permanent threshold shift (PTS) and is thought to be associated with early onset of age-related hearing loss (ARHL). The possibility that a PTS might be induced by administration of repeated TTS-inducing noise exposures (NEs) over a short period during early adulthood has not been formally investigated. We aimed to investigate possible cumulative acoustic overstimulation effects that permanently shift the auditory threshold. ⋯ The pattern of PTS resembled NIHL since the observed impairments tonotopically followed the power spectrum of the noise insult, rather than ARHL, which distributes at higher frequencies. No significant changes were observed in the control group as the mice aged. To conclude, our results demonstrate a cumulative effect of repetitive TTS-inducing NE on hearing function and synaptic plasticity that does not cause premature ARHL, thereby providing insight into the pathophysiological mechanisms underlying NIHL and ARHL.
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The primary cause of harmaline tremor, which is a model of essential tremor (ET) in animals, is excessive activation of olivocerebellar glutamatergic climbing fibers. Our recent study indicated that 5'-chloro-5'-deoxy-(±)-N6-(±)-(endo-norborn-2-yl)adenosine (5'Cl5'd-(±)-ENBA), a potent and selective adenosine A1 receptor (A1) agonist, inhibited harmaline tremor. The present study was aimed to evaluate the role of glutamatergic transmission system in 5'Cl5'd-(±)-ENBA tremorolytic action in the harmaline model in rats, by analyzing glutamate release in the motor nuclei of the thalamus and mRNA expression of glutamatergic neuron markers (vGlut1/2) in reference to the general neuronal activity marker (zif-268) in different brain structures. ⋯ The intensity of tremor was measured automatically using Force Plate Actimeters (FPAs). 5'Cl5'd-(±)-ENBA (0.5 mg/kg) given 30 min before harmaline (30 mg/kg) decreased the harmaline-induced excessive glutamate release in the motor thalamus and reversed harmaline-induced molecular effects, such as elevation of the vGlut1 mRNA expression in the inferior olive (IO) and decrease in the motor cortex, as well as an increase of the zif-268 mRNA expression in the IO, motor thalamus and motor cortex. Moreover, 5'Cl5'd-(±)-ENBA reduced harmaline tremor by lowering its power in 9-15 Hz frequency band. Our findings show that A1 stimulation decreases glutamate release in the motor thalamic nuclei in the harmaline model of ET, suggesting that A1 receptors, especially in this structure, may be a potential therapeutic target in this disorder.
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In this study we used functional MRI (fMRI) to examine whether defining a stimulus as a target affects brain activation associated with a verbal working memory (WM) task. Seventeen healthy right-handed volunteers performed a Sternberg task with three consonants as memory set. We performed a region of interest based fMRI analysis to examine differences in brain activity patterns between targets and non-targets. ⋯ Our results suggest an important hemispheric differentiation in target processing, in which the right frontal cortex is predominantly involved in processes associated with target stimuli. The left frontal cortex does not differentiate between processing target and non-target stimuli, suggesting involvement in WM processes that are independent of stimulus type. Parietal, the lateral anterior part is predominantly involved in target processing, while the medial posterior part does not differentiate between target and non-target processing.
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Itch (pruritus), specifically chronic itch associated with disease conditions, significantly impairs the patient's quality of life. At present, the mechanisms underlying this aversive experience are still unclear, and the effective treatment of itch is largely unmet. Here, we report that intragastrical administration of bulleyaconitine A (BLA), which has been used for treating chronic pain for 30 years in China, inhibited itch-like behaviors induced by intradermal injection of histamine and chloroquine in mice and rats, dose-dependently. ⋯ The behavioral change was accompanied with the potentiation of C-fiber synaptic transmission in the dorsal horn. Both the itch sensitization and synaptic potentiation were substantially attenuated by intragastrical BLA. Together, BLA was effective in inhibiting histamine-dependent and histamine-independent itches, and the mechanisms underlying these effects were involved but not limited to the inhibition of gastrin-releasing peptide (GRP)-GRPR signaling in the spinal dorsal horn.