74 research outputs found

    Spine neck plasticity regulates compartmentalization of synapses

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    Dendritic spines have been proposed to transform synaptic signals through chemical and electrical compartmentalization. However, the quantitative contribution of spine morphology to synapse compartmentalization and its dynamic regulation are still poorly understood. We used time-lapse super-resolution stimulated emission depletion (STED) imaging in combination with fluorescence recovery after photobleaching (FRAP) measurements, two-photon glutamate uncaging, electrophysiology and simulations to investigate the dynamic link between nanoscale anatomy and compartmentalization in live spines of CA1 neurons in mouse brain slices. We report a diversity of spine morphologies that argues against common categorization schemes and establish a close link between compartmentalization and spine morphology, wherein spine neck width is the most critical morphological parameter. We demonstrate that spine necks are plastic structures that become wider and shorter after long-term potentiation. These morphological changes are predicted to lead to a substantial drop in spine head excitatory postsynaptic potential (EPSP) while preserving overall biochemical compartmentalization

    Subcellular Location of PKA Controls Striatal Plasticity: Stochastic Simulations in Spiny Dendrites

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    Dopamine release in the striatum has been implicated in various forms of reward dependent learning. Dopamine leads to production of cAMP and activation of protein kinase A (PKA), which are involved in striatal synaptic plasticity and learning. PKA and its protein targets are not diffusely located throughout the neuron, but are confined to various subcellular compartments by anchoring molecules such as A-Kinase Anchoring Proteins (AKAPs). Experiments have shown that blocking the interaction of PKA with AKAPs disrupts its subcellular location and prevents LTP in the hippocampus and striatum; however, these experiments have not revealed whether the critical function of anchoring is to locate PKA near the cAMP that activates it or near its targets, such as AMPA receptors located in the post-synaptic density. We have developed a large scale stochastic reaction-diffusion model of signaling pathways in a medium spiny projection neuron dendrite with spines, based on published biochemical measurements, to investigate this question and to evaluate whether dopamine signaling exhibits spatial specificity post-synaptically. The model was stimulated with dopamine pulses mimicking those recorded in response to reward. Simulations show that PKA colocalization with adenylate cyclase, either in the spine head or in the dendrite, leads to greater phosphorylation of DARPP-32 Thr34 and AMPA receptor GluA1 Ser845 than when PKA is anchored away from adenylate cyclase. Simulations further demonstrate that though cAMP exhibits a strong spatial gradient, diffusible DARPP-32 facilitates the spread of PKA activity, suggesting that additional inactivation mechanisms are required to produce spatial specificity of PKA activity

    Interdependence between transportation system and power distribution system: a comprehensive review on models and applications

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    The rapidly increasing penetration of electric vehicles in modern metropolises has been witnessed during the past decade, inspired by financial subsidies as well as public awareness of climate change and environment protection. Integrating charging facilities, especially high-power chargers in fast charging stations, into power distribution systems remarkably alters the traditional load flow pattern, and thus imposes great challenges on the operation of distribution network in which controllable resources are rare. On the other hand, provided with appropriate incentives, the energy storage capability of electric vehicle offers a unique opportunity to facilitate the integration of distributed wind and solar power generation into power distribution system. The above trends call for thorough investigation and research on the interdependence between transportation system and power distribution system. This paper conducts a comprehensive survey on this line of research. The basic models of transportation system and power distribution system are introduced, especially the user equilibrium model, which describes the vehicular flow on each road segment and is not familiar to the readers in power system community. The modelling of interdependence across the two systems is highlighted. Taking into account such interdependence, applications ranging from long-term planning to short-term operation are reviewed with emphasis on comparing the description of traffic-power interdependence. Finally, an outlook of prospective directions and key technologies in future research is summarized.fi=vertaisarvioitu|en=peerReviewed

    Cholecystokinin- and Melatonin-receptors in human and rat salivary glands

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    Recent observations of ours show the rat parotid gland to respond, in vivo, to gastrin, cholecystokinin and melatonin with protein secretion, without any accompanying overt fluid secretion. Moreover, we do also find pieces of human parotid tissue to secrete protein in vitro and to display ultrastructural changes associated with secretory activity. OBJECTIVES: To visualize the receptor-substrate for the action of these hormones in parotid, submandibular and sublingual glands of humans and rats. METHODS: Immunochemistry was applied, using antibodies for cholecystokinin (CCK)-A, CCK-B and melatonin 2-receptors (including negative controls). The sections were examined under light microscopy. The specimens from humans were obtained at benign salivary gland surgery (15 patients), while glands of 8 rats of both sexes were used. RESULTS: The pattern of immunoreactivity was similar in humans and rats. In all types of glands, the acinar serous cells (but not the mucous cells) and the striated duct cells stained for the three receptors under study. The staining for CCK-A receptors of acinar cells was stronger than for duct cells, while the opposite was the case for the two other receptors. CONCLUSION: A hormonal influence on the secretory activity of salivary glands may be a general phenomenon. In response to a meal, the glands are probably not only regulated by the well-known cephalic phase (nerves) but also by a gastric (gastrin) and an intestinal phase (cholecystokinin and melatonin), the three phases overlapping each other
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