Neuroscience
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Afferent connections to the sensory inner (IHCs) and outer hair cells (OHCs) in the cochlea refine and functionally mature during the thyroid hormone (TH)-critical period of inner ear development that occurs perinatally in rodents. In this study, we investigated the effects of hypothyroidism on afferent type II innervation to outer hair cells using the Snell dwarf mouse (Pit1(dw)). Using a transgenic approach to specifically label type II spiral ganglion neurons (SGNs), we found that lack of TH causes persistence of excess type II SGN connections to the OHCs, as well as continued expression of the hair cell functional marker, otoferlin (OTOF), in the OHCs beyond the maturation period. ⋯ Supplementing with TH during the early postnatal period from postnatal day (P) 3 to P4 reversed the defect in type II SGN pruning but did not alter OTOF expression. Our results show that hypothyroidism causes a defect in the large-scale pruning of afferent type II SGNs in the cochlea, and a delay in efferent attachment and the maturation of OTOF expression. Our data suggest that the state of maturation of hair cells, as determined by OTOF expression, may not regulate the pruning of their afferent innervation.
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Delivering effective commands in the nervous systems require a temporal integration of neural activities such as synchronous firing. Although sympathetic nerve discharges are characterized by synchronous firing, its temporal structures and how it is modulated are largely unknown. This study used a collagenase-dissociated splanchnic sympathetic nerve-thoracic spinal cord preparation of neonatal rats in vitro as an experimental model. ⋯ Antagonist-induced enhancement and attenuation of correlated firing were demonstrated by a respective increase and decrease of the peak probability of the cross-correlograms. Heterogeneity in antagonistic responses suggests that the inhibitory neurotransmission mediated by GABA(A) and glycine receptors is not essential for but can serve as a neural substrate to modulate synchronous firing behaviors. Plausible neural mechanisms were proposed to explain the temporal structures of correlated firing between sympathetic fibers.
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Creatine supplementation has been shown to protect neurons from oxidative damage due to its antioxidant and ergogenic functions. These features have led to the hypothesis of creatine supplementation use during pregnancy as prophylactic treatment to prevent CNS damage, such as hypoxic-ischemic encephalopathy. Unfortunately, very little is known on the effects of creatine supplementation during neuron differentiation, while in vitro studies revealed an influence on neuron excitability, leaving the possibility of creatine supplementation during the CNS development an open question. ⋯ Consistently, CA1 neurons of creatine exposed pups exhibited a higher maximum firing frequency than controls. In summary, we found that creatine supplementation during pregnancy positively affects morphological and electrophysiological development of CA1 neurons in offspring rats, increasing neuronal excitability. Altogether, these findings emphasize the need to evaluate the benefits and the safety of maternal intake of creatine in humans.
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Chronic exposure to low-dose 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in marmoset monkeys was used to model the prodromal stage of Parkinson's disease (PD), and to investigate mechanisms underlying disease progression and recovery. Marmosets were subcutaneously injected with MPTP for a period of 12weeks, 0.5mg/kg once per week, and clinical signs of Parkinsonism, motor- and non-motor behaviors were recorded before, during and after exposure. In addition, postmortem immunohistochemistry and proteomics analysis were performed. ⋯ Also levels of TH in putamen and caudate nucleus were unaltered, no differences were observed in DA, serotonin or nor-adrenalin levels in the caudate nucleus, and proteomics analysis revealed no global changes in protein expression in these brain areas between treatment groups. Our findings indicate that parkinsonian symptoms can occur without detectable damage at the cellular or molecular level. Moreover, we show that parkinsonian symptoms may be reversible when diagnosed and treated early.
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To investigate the feedback effect from area 7 to areas 17 and 18, intrinsic signal optical imaging combined with pharmacological, morphological methods and functional magnetic resonance imaging (fMRI) was employed. A spatial frequency-dependent decrease in response amplitude of orientation maps was observed in areas 17 and 18 when area 7 was inactivated by a local injection of GABA, or by a lesion induced by liquid nitrogen freezing. ⋯ Employing fMRI it was found that area 7 feedbacks mainly to areas 17 and 18 on ipsilateral hemisphere. Therefore, our conclusions are: (1) feedback from area 7 to areas 17 and 18 is spatial frequency modulated; (2) feedback from area 7 to areas 17 and 18 occurs mainly ipsilaterally; (3) histological feedback pattern from area 7 to area 17 is weblike.