Neuroscience
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Despite the long history of investigations of adrenergic compounds and their biological effects, specific mechanisms of their action in distinct compartments of the motor unit remain obscure. Recent results have suggested that not only skeletal muscles but also the neuromuscular junctions represent important targets for the action of catecholamines. In this paper, we describe the effects of adrenaline and noradrenaline on the frequency of miniature endplate potentials, the quantal content of the evoked endplate potentials and the kinetics of acetylcholine quantal release in the motor nerve endings of the mouse diaphragm. ⋯ Quantal release became more asynchronous under noradrenaline, as evidenced by a greater dispersion of real synaptic delays; in contrast, adrenaline synchronized the release process. Our data suggest an involvement of α and β adrenoreceptors in the diverse modulation of the frequency of miniature endplate potentials, the quantal content of the evoked endplate potentials and the kinetics of acetylcholine quantal secretion in the mouse neuromuscular junction. Moreover, the adrenoblockers affected both the evoked and spontaneous quantal release of acetylcholine, suggesting the presence of endogenous catecholamines in the vicinity of cholinergic synapses.
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The vestibular system of the inner ear contains Type I and Type II hair cells (HCs) generated from sensory progenitor cells; however, little is known about how the HC subtypes are formed. Sox2 (encoding SRY-box 2) is expressed in Type II, but not in Type I, HCs. The present study aimed to investigate the role of SOX2 in cell fate determination in Type I vs. ⋯ These results demonstrate that SOX2 plays a critical role in the determination of Type II vs. Type I HC fate. The results suggested that Sox2 is a potential target for generating Type I HCs, which may be important for regenerative strategies for balance disorders.
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Noise-induced hearing loss generally induces loudness recruitment, but sometimes gives rise to hyperacusis, a debilitating condition in which moderate intensity sounds are perceived abnormally loud. In an attempt to develop an animal model of loudness hyperacusis, we exposed rats to a 16-20 kHz noise at 104 dB SPL for 12 weeks. Behavioral reaction time-intensity functions were used to assess loudness growth functions before, during and 2-months post-exposure. ⋯ Consistent with central gain models, the gross neural responses from the auditory cortex and amygdala were proportionately much larger than those from the cochlea. However, despite central amplification, the population responses in the auditory cortex and amygdala were still below the level needed to fully account for hyperacusis and/or recruitment. Having developed procedures that can consistently induce hyperacusis in rats, our results set the stage for future studies that seek to identify the neurobiological events that give rise to hyperacusis and to develop new therapies to treat this debilitating condition.
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Low frequency phase synchronization is an essential mechanism of information communication among brain regions. In the infra-slow frequency range (<0.1 Hz), inter-regional phase lag is of importance for brain function (e.g., anti-phase between the default mode network and task positive network). However, the role of phase lag in cognitive processing remains unclear. ⋯ Inter-regional phase lag was modulated by the task at ascending and descending phases of the fMRI signal, suggesting a phase-dependent inter-regional relationship. Furthermore, phase lags between visual cortex and amygdala and between visual cortex and motor area were positively related to reaction time, indicating better task performance depends on both rapid emotional detection pathway and visual-motor pathway. Overall, inter-regional phase synchronization in the infra-slow frequency range is of important for effective information communication and cognitive performance.
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Growing evidence indicates that early-life inflammation has adverse effects on adult hippocampal neurogenesis and GABA system. Based the report that hippocampal GABA system is a key modulator in adult hippocampal neurogenesis, the aim of this study was to investigate whether and how early inflammation affects GABAergic system resulting in the alterations of adult hippocampal neurogenesis and related behaviors. Neonatal mice received a daily subcutaneous injection of lipopolysaccharide (LPS, 50 μg/kg) or saline on postnatal days (PND) 3-5. ⋯ Additionally, postnatal LPS treatment resulted in the activation of astrocytes and the increase expression of toll-like receptor 4 (TLR4) in the second postnatal week and the downregulation of BDNF-TrkB pathway in adulthood. The treatment with TLR4 inhibitor TAK-242 restored the decrease of BrdU+/NeuN+ cells and depression-like behaviors in LPS mice via improving GABAAR. The results indicate that postnatal LPS exposure impairs adult hippocampal neurogenesis and causes depression-like behaviors through early astrocytes activation triggering the later GABAAR downregulation.