Neuroscience
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Behavioral flexibility is known to be mediated by corticostriatal systems and to involve several major neurotransmitter signaling pathways. The current study investigated the effects of inactivation of glutamatergic N-methyl-D-aspartate-(NMDA) receptor signaling in the dorsal striatum on behavioral flexibility in mice. NMDA-receptor inactivation was achieved by virus-mediated inactivation of the Grin1 gene, which encodes the essential NR1 subunit of NMDA receptors. ⋯ Inactivation of NMDA-receptors in all neurons of the dorsal striatum did not affect learning of the initial rule or reversal learning, but impaired shifting from one strategy to another. Strategy shifting was also compromised when NMDA-receptors were inactivated only in dynorphin-expressing neurons in the dorsal striatum, which represent the direct pathway. These data suggest that NMDA-receptor-mediated synaptic plasticity in the dorsal striatum contributes to strategy shifting and that striatal projection neurons of the direct pathway are particularly relevant for this process.
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Neuromodulators rapidly alter activity of neural circuits and can therefore shape higher order functions, such as sensorimotor integration. Increasing evidence suggests that brain-derived estrogens, such as 17-β-estradiol, can act rapidly to modulate sensory processing. However, less is known about how rapid estrogen signaling can impact downstream circuits. ⋯ These effects were not due to direct estradiol actions because NIf has little to no capability for local estrogen synthesis or estrogen receptors, and these effects were specific to NIf because other neurons immediately surrounding NIf did not show these changes. Our results demonstrate that transsynaptic, rapid fluctuations in neuroestrogens are transmitted into NIf and subsequently HVC, both regions important for sensorimotor integration. Overall, these findings support the hypothesis that acute neurosteroid actions can propagate within and between neural circuits to modulate their functional connectivity.
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Autism is a severe neurodevelopmental disorder characterized by impairments in social interaction and repetitive behaviors. Diagnosis of autism is currently phenotype based with no reliable laboratory test available to assist clinicians. It has been shown that dysfunction of serotonin (5-HT) and interleukin-6 (IL-6) are involved in autism. ⋯ The whole blood concentration of 5-HT and plasma concentration of IL-6 of individuals with autism were significantly elevated compared with the control group, and the concentration of 5-HT and IL-6 had positive correlations with the severity of autism. The results of receiver operating characteristic (ROC) analysis indicated that the combination of 5-HT and IL-6 produced the best sensitivity and specificity for diagnosis of autism. Therefore, the present study has revealed a simple clinical method with great potential for assisting the diagnosis of autism.
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Human auditory nerve afferents consist of two separate systems; one is represented by the large type I cells innervating the inner hair cells and the other one by the small type II cells innervating the outer hair cells. Type I spiral ganglion neurons (SGNs) constitute 96% of the afferent nerve population and, in contrast to other mammals, their soma and pre- and post-somatic segments are unmyelinated. Type II nerve soma and fibers are unmyelinated. ⋯ Their BMs express laminin-β2/collagen IV and reaches the BM of the sensory epithelium at the habenula perforata. We speculate that the NMSCs protect SGNs from further degeneration following dendrite loss. It may give further explanation why SGNs can persist as electrically excitable monopolar cells even after long-time deafness, a blessing for the deaf treated with cochlear implantation.
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The 70-kDa heat shock protein (HSP70) is known to protect the brain from injury through multiple mechanisms. We investigated the effect of pharmacological HSP70 induction in experimental traumatic brain injury (TBI). 3-month-old male C57/B6 mice were given 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) intraperitoneally (IP, 2 mg/kg) or intracerebroventricularly (ICV, 1 μg/kg) to determine whether HSP70 could be induced in the brain. Mice were subjected to TBI via cortical controlled impact, and were treated with 17-AAG (or vehicle) IP according to one of two treatment regimens: (1) 2 mg/kg at the time of injury, (2) a total of three doses (4 mg/kg) at 2 and 1d prior to TBI and again at the time of injury. ⋯ Immunohistochemistry showed that both IP and ICV administration of 17-AAG increased HSP70 expression primarily in microglia and in a few neurons by 24 h but not in astrocytes. 17-AAG induced HSP70 in injured brain tissue as early as 6 h, peaking at 48 h and largely subsiding by 72 h after IP injection. Both treatment groups showed decreased hemorrhage volume relative to untreated mice as well as improved neurobehavioral outcomes. These observations indicate that pharmacologic HSP70 induction may prove to be a promising treatment for TBI.