Hearing loss is a major risk factor for tinnitus, hyperacusis, and central auditory processing disorder. Although recent studies indicate that hearing loss causes neuroinflammation in the auditory ...pathway, the mechanisms underlying hearing loss-related pathologies are still poorly understood. We examined neuroinflammation in the auditory cortex following noise-induced hearing loss (NIHL) and its role in tinnitus in rodent models. Our results indicate that NIHL is associated with elevated expression of proinflammatory cytokines and microglial activation-two defining features of neuroinflammatory responses-in the primary auditory cortex (AI). Genetic knockout of tumor necrosis factor alpha (TNF-α) or pharmacologically blocking TNF-α expression prevented neuroinflammation and ameliorated the behavioral phenotype associated with tinnitus in mice with NIHL. Conversely, infusion of TNF-α into AI resulted in behavioral signs of tinnitus in both wild-type and TNF-α knockout mice with normal hearing. Pharmacological depletion of microglia also prevented tinnitus in mice with NIHL. At the synaptic level, the frequency of miniature excitatory synaptic currents (mEPSCs) increased and that of miniature inhibitory synaptic currents (mIPSCs) decreased in AI pyramidal neurons in animals with NIHL. This excitatory-to-inhibitory synaptic imbalance was completely prevented by pharmacological blockade of TNF-α expression. These results implicate neuroinflammation as a therapeutic target for treating tinnitus and other hearing loss-related disorders.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Scanpaths (the succession of fixations and saccades during spontaneous viewing) contain information about the image but also about the viewer. To determine the viewer-dependent factors in the ...scanpaths of monkeys, we trained three adult males (Macaca mulatta) to look for 3 s at images of conspecific facial expressions with either direct or averted gaze. The subjects showed significant differences on four basic scanpath parameters (number of fixations, fixation duration, saccade length, and total scanpath length) when viewing the same facial expression/gaze direction combinations. Furthermore, we found differences between monkeys in feature preference and in the temporal order in which features were visited on different facial expressions. Overall, the between-subject variability was larger than the within- subject variability, suggesting that scanpaths reflect individual preferences in allocating visual attention to various features in aggressive, neutral, and appeasing facial expressions. Individual scanpath characteristics were brought into register with the genotype for the serotonin transporter regulatory gene (5-HTTLPR) and with behavioral characteristics such as expression of anticipatory anxiety and impulsiveness/hesitation in approaching food in the presence of a potentially dangerous object.
Fragile X syndrome, the most common form of heritable mental retardation, is a developmental disorder with known effects within sensory systems. Altered developmental plasticity has been reported in ...the visual and somatosensory systems in Fmr1 knock-out (KO) mice. Behavioral studies have revealed maladaptive auditory responses in fragile X syndrome patients and Fmr1 KO mice, suggesting that adaptive plasticity may also be impaired in the auditory system. Here we show that, whereas tonotopic frequency representation develops normally in Fmr1 KO mice, developmental plasticity in primary auditory cortex is grossly impaired. This deficit can be rescued by pharmacological blockade of mGluR5 receptors. These results support the mGluR hypothesis of fragile X mental retardation and suggest that deficient developmental plasticity may contribute to maladaptive auditory processing in fragile X syndrome.
Graphical abstract Highlights ► Rat pups were exposed to pulsed tone from postnatal days 9 to 25. ► Exposure did not alter the frequency map in the central nucleus of the inferior colliculus (ICC). ► ...Exposure led to transient narrowing of the tuning bandwidth in the ICC. ► Exposure changed the frequency map in the primary auditory cortex. ► Conclusion: cortical map reorganization is not due to subcortical changes.
Early experience shapes sensory representations in a critical period of heightened plasticity. This adaptive process is thought to involve both Hebbian and homeostatic synaptic plasticity. Although ...Hebbian plasticity has been investigated as a mechanism for cortical map reorganization, less is known about the contribution of homeostatic plasticity. We investigated the role of homeostatic synaptic plasticity in the development and refinement of frequency representations in the primary auditory cortex using the tumor necrosis factor-α (TNF-α) knockout (KO), a mutant mouse with impaired homeostatic but normal Hebbian plasticity. Our results indicate that these mice develop weaker tonal responses and incomplete frequency representations. Rearing in a single-frequency revealed a normal expansion of cortical representations in KO mice. However, TNF-α KOs lacked homeostatic adjustments of cortical responses following exposure to multiple frequencies. Specifically, while this sensory over-stimulation resulted in competitive refinement of frequency tuning in wild-type controls, it broadened frequency tuning in TNF-α KOs. Our results suggest that homeostatic plasticity plays an important role in gain control and competitive interaction in sensory cortical development.
A whole-blood test for total cholesterol has been developed that is performed in a low-cost disposable flow device without user intervention (after sample addition). The device meters the sample, ...separates plasma from erythrocytes, and precisely times plasma flow into various reagent compartments, including a quality-assurance chamber. Test results are displayed as a well-defined and easily readable color bar. A quality-control window attests to the integrity of the test components. Here, we describe the assembly and individual functions of the device and report its performance characteristics. Precision and accuracy studies in four clinical studies at independent locations yielded total imprecision of <5% and an average bias of 1.35% vs the Abell-Kendall method.
PDF
