Plasticity of auditory electrical synapses
听觉电突触的可塑性
基本信息
- 批准号:9310995
- 负责人:
- 金额:$ 60.3万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2010
- 资助国家:美国
- 起止时间:2010-07-01 至 2022-01-31
- 项目状态:已结题
- 来源:
- 关键词:AdultAnatomyAuditoryAuditory systemBehaviorCellsChemical SynapseChemicalsChemosensitizationCommunicationComplementComplexConnexinsDNA Sequence AlterationDataDopamineElectrical SynapseElectron MicroscopyElectrophysiology (science)ExcisionFishesFreezingFunctional disorderGap JunctionsGoldfishImageLarvaLifeM cellMediatingMethodsMicroscopyModelingModificationMolecularMonitorMovementNeuromodulatorNeurotransmitter ReceptorOpticsPharmacologyPlasticizersPropertyProteinsProtocols documentationRegulationReportingResearchScaffolding ProteinStructureSynapsesSynaptic TransmissionTestingTimeTransgenic OrganismsWorkZebrafishauditory pathwayauditory processingbasedorsal cochlear nucleuselectrical propertygap junction channelgenetic manipulationgenetic regulatory proteinin vivoin vivo imaginginformation processingmembrane fluxneural circuitneuronal circuitrynew therapeutic targetnoveloptogeneticsrelating to nervous systemtraffickingtransmission process
项目摘要
Abstract
Gap junction (GJ)-mediated electrical synapses were recently reported to underlie important network
properties in the dorsal cochlear nucleus and anatomical evidence suggests they are widespread along the
auditory pathway. However, the properties of auditory electrical synapses remain poorly understood. As their
chemical counterparts, electrical synapses are ‘plastic’, that is, they modify their strength with activity. Changes
in the strength of electrical synapses dynamically reconfigure neuronal circuits in various neural structures.
Thus, the presence and plastic properties of electrical synapses could fundamentally change the way we
understand the organization of auditory circuits and, ultimately, the processing of auditory information. This
proposal aims to contribute to our understanding of electrical transmission in the auditory system by
investigating the molecular mechanisms causing plastic changes in GJ communication at mixed, electrical and
chemical, contacts that couple primary auditory afferents to the Mauthner (M-) cells in fish. Our work in goldfish
shows that electrical (and chemical) transmission at these mixed synapses undergo activity-dependent
potentiation. Because these dynamic properties were later found to occur at mammalian electrical synapses.
M-cell mixed synapses are considered a valuable model to study plasticity of vertebrate electrical transmission.
In contrast to chemical synapses, little is known about the molecular mechanisms that underlie changes in the
strength of electrical synapses. It is currently thought that plastic changes in GJ conductance are due to direct
modification of the properties of already existing channels. However, our progress suggests that regulated
insertion and removal of GJ channels may also contribute to plasticity. We propose to investigate the
contribution of regulated trafficking of GJ channels to plastic changes of electrical transmission and its
molecular underpinnings. To directly examine this possibility, we will take these unique model mixed synapses
to a new level of analysis by investigating their properties in larval zebrafish. The amenability of zebrafish
larvae to image the movement of fluorescently-tagged GJ channels in-vivo should allow monitoring of active
synapses undergoing plasticity. This approach will provide an unprecedented window for the analysis of
electrical transmission at which detailed molecular mechanisms will be investigated by combining in-vivo
imaging, electrophysiology and time-resolved ultrastructural analysis with powerful genetic manipulations. Aim
1 is to investigate the conditions under which electrical synapses in larval zebrafish undergo potentiation. By
combining electrophysiology and pharmacology with electrical and optogenetic stimulation, this aim will identify
the conditions under which larval mixed synapses undergo potentiation of electrical (and chemical)
transmission. Aim 2 is to test whether insertion and removal of GJ channels are required for plastic changes.
This aim will explore the notion that electrical synapses are complex synaptic structures at which channels
turnover and that their proper function and regulation results from interactions between multiple proteins. The
description of novel molecular mechanisms involved in their regulation will contribute to a better understanding
of the dynamics of circuits relevant to auditory dysfunction and the potential identification of novel therapeutic
targets.
摘要
项目成果
期刊论文数量(0)
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Alberto E Pereda其他文献
Alberto E Pereda的其他文献
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{{ truncateString('Alberto E Pereda', 18)}}的其他基金
Generation of transgenic zebrafish to study electrical synaptic transmission
产生转基因斑马鱼以研究电突触传递
- 批准号:
9197389 - 财政年份:2013
- 资助金额:
$ 60.3万 - 项目类别:
Generation of transgenic zebrafish to study electrical synaptic transmission
产生转基因斑马鱼以研究电突触传递
- 批准号:
8623965 - 财政年份:2013
- 资助金额:
$ 60.3万 - 项目类别:
Generation of transgenic zebrafish to study electrical synaptic transmission
产生转基因斑马鱼以研究电突触传递
- 批准号:
8735205 - 财政年份:2013
- 资助金额:
$ 60.3万 - 项目类别:
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