Neuroscience
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The perirhinal (PER) - lateral entorhinal (LEC) network plays a pivotal role in the information transfer between the neocortex and the hippocampus. Anatomical studies have shown that the connectivity is organized bi-directionally: the superficial layers consist of projections running from the neocortex via the PER-LEC network to the hippocampus while the deep layers form the output pathway back to the neocortex. Although these pathways are characterized anatomically, the functional organization of the superficial and deep connections in the PER-LEC network remains to be revealed. ⋯ We performed paired recordings in superficial layer principal neurons and parvalbumin (PV) expressing interneurons to address how this window of opportunity for spiking is affected in superficial principal neurons. The PV interneuron population initiated inhibition at a very consistent timing with increasing stimulus intensity, whereas the excitation temporally shifted to ensure action potential firing. These data indicate that superficial principal neurons can transmit cortical synaptic input through the PER-LEC network because these neurons have a favorable window of opportunity for spiking in contrast to deep neurons.
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The sphenopalatine ganglion (SPG) is a gathering of the cell bodies of parasympathetic fibers that dominate the nasal gland, lacrimal gland and cerebral blood vessels. The SPG controls nasal secretions, tears, and the dilation of cerebral blood vessels. However, it is unclear how serotonin regulates SPG functions. ⋯ The 5-HT3A receptor, 5-HT3B receptor, and AADC were expressed in 96.5% ± 1.0%, 29.7% ± 10.7%, and 57.4% ± 2.9% of neuronal cell bodies in the SPG, respectively, indicating that the 5-HT3A receptor was virtually expressed in all SPG neurons. Our results on the expression of these critical serotonin system genes in the parasympathetic SPG provide insight into the pathogenetics of rhinitis, conjunctivitis and headache. Furthermore, our findings suggest that targeting the 5-HT3A receptor might have therapeutic potential in the treatment of these ailments.
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Elevated blood serotonin in perinatal development is the most consistent neurochemical finding reported in Autism Spectrum Disorder (ASD), and has been implicated in the pathogenesis of the disorder. Accordingly, pre- and postnatal administration of the non-selective serotonin agonist, 5-methoxytryptamine (5-MT), is hypothesized as a model of developmental hyperserotonemia (DHS) to investigate the behavioral and morphological implications in ASD. Our previous study, examining the effects of DHS, found significant neuroanatomical changes in the dendritic architecture and connectivity of neurons in the dentate nucleus of the cerebellum. ⋯ While results did not show a change in the overall volume of the thalamus, when grouped by estimated total brain volume, the mean thalamic volume was significantly reduced in the DHS group relative to controls. Additionally, significant reductions in cell numbers, density and distribution were observed in subdivisions of the principle nuclei including the ventral anterior, ventral lateral, ventral posterolateral, and ventral posteromedial nuclei. Alterations in these areas and their reciprocal connections throughout the brain may effect neuronal organization and be implicated in the neuropathological and behavioral changes observed in ASD.
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Spastin is a microtubule-severing enzyme encoded by SPAST, which is broadly expressed in various cell types originated from multiple organs. Even though SPAST is well known as a regulator of the axon growth and arborization in neurons and a genetic factor of hereditary spastic paraplegia, it also takes part in a wide range of other cellular functions including the regulation of cell division and proliferation. In this study, we investigated a novel biological role of spastin in developing brain using Spast deficient mouse embryonic neural stem cells (NSCs) and perinatal mouse brain. ⋯ Using Spast shRNA treated NSCs and mouse brain, we showed that Spast deficiency leads to decrease of NSC proliferation and neuronal lineage differentiation. Finally, we found that spastin controls NSC proliferation by regulating microtubule dynamics in primary cilia. Collectively, these data demonstrate that spastin controls brain development by the regulation of NSC functions at early developmental stages.