Neuroscience
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Very slow fluctuations of spontaneous activities significantly influence not only behavioral performance in a conscious state, but also neural activities in an unconscious state. Covariation of pupil and cortical activities may lend important insights into the state-dependent modulation of stimulus encoding, yet this phenomenon has received little attention, especially with regard to non-visual cortices. In the present study, we investigated co-fluctuation of pupil size and neural activity in the auditory cortex of rats under isoflurane anesthesia. ⋯ Furthermore, light exposure induced the pupil reflex through the autonomic system, but did not modify cortical activity, indicating that autonomic activity was not causing the cortical modulation. These results together suggest that cortical activities spontaneously covary with pupillary activity through central cholinergic modulation that triggers sympathetic nerve activation. Such a state-dependent property may be a confounding factor in cortical electrophysiology studies.
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Our previous study has proved that glucagon-like peptide-1 (GLP-1), which is developed to treat type 2 diabetes, has a significant effect on neuroprotection against advanced glycation end product (AGE)-induced neuronal insult in vitro models of diabetes-related Alzheimer's disease (AD). However, the molecular mechanisms remain to be elucidated and it is not clear whether GLP-1 receptor mediates the down-regulation effects on AGE-induced AD-like changes in vivo. This study aims to explore the effect and mechanisms of GLP-1 receptor agonists (GLP-1RA) against the AGE-dependent signaling pathway both in vitro and in vivo. ⋯ Importantly, we first observed AGEs in the circulatory system could induce tau hyperphosphorylation after we injected AGEs (1μg/kg bodyweight) into the mice tail vein. We found GLP-1RA could promote mitochondrial biogenesis and antioxidant system via regulating peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) signaling pathway in vivo besides down-regulating the activity of glycogen synthase kinase 3β (GSK-3β) to reverse tau hyperphosphorylation directly. Collectively, our results suggest that GLP-1RA protects neurons against AGE-induced tau hyperphosphorylation via regulating GSK-3β and PGC-1α two cooperative signaling pathways.
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The bed nucleus of the stria terminalis (BST) is part of the limbic system located in the rostral forebrain. BST is involved in behavioral, neuroendocrine and autonomic functions, including cardiovascular regulation. The angiotensin II (Ang II) receptor, AT1, was found in the BST, however its effects on the cardiovascular system and on single-unit responses have not been studied yet. ⋯ It also produced two types of single-unit responses in the BST, short excitatory and long inhibitory. Blockade of AT1 receptors abolished both the cardiovascular and single-unit responses, indicating that the responses were mediated through AT1 receptors. These findings imply that Ang II may be utilized as a neurotransmitter and may play a role in returning blood pressure toward normal during hypotension.
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Proliferation and differentiation of retinal progenitor cells (RPCs) are tightly controlled by extrinsic cues and distinct combinations of transcription factors leading to the generation of retinal cell type diversity. In this context, we investigated the role of the protein tyrosine phosphatase interacting protein 51 (PTPIP51) in the differentiation of RPCs. The expression pattern of PTPIP51 was analyzed by immunostaining during post-natal retinal development in the rat. ⋯ By contrast, misexpression of PTPIP51 in early or late RPCs failed to modify the differentiation of the RPCs. Our data demonstrate that PTPIP51 is implicated in the differentiation process of immature photoreceptors. Because PTPIP51 is specifically localized in the inner segment, PTPIP51 may contribute to the complex stage of maturation of the apical segment of these cells.
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Updating the position of an earth-fixed target during whole-body rotation seems to rely on cognitive processes such as the utilization of external feedback. According to perceptual learning models, improvement in performance can also occur without external feedback. The aim of this study was to assess spatial updating improvement in the absence and in the presence of external feedback. ⋯ However, no group difference was observed for the untrained direction (p=0.22). We demonstrated that spatial updating improved without external feedback but less than when external feedback was given. These observations are explained by a mixture of calibration processes and supervised vestibular learning.