Signaling to and from the Synapse

进出突触的信号

• 批准号: 7692210
• 负责人: Richard L Huganir
• 金额: $ 188.68万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-24 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7692210
• 关键词: AMPA Receptors; Address; Affect; Astrocytes; Attenuated; Axon; Back; Bacterial Artificial Chromosomes; Behavior; Binding; Biochemical; Biological Models; Brain; Breeding; CDK9 Protein Kinase; Calcium; Calcium Signaling; Caring; Cell Death; Cell Nucleus; Cell division; Cells; Collaborations; Complementary DNA; Complex; Core Facility; Coupling; DAP kinase; Daughter; Defect; Dendrites; Development; Disease; Dopamine Receptor; Drug Addiction; Event; Excitatory Synapse; Exhibits; Gene Expression; Genes; Genetic Transcription; Genomic Library; Genomics; Genotype; Glutamate Transporter; Glutamates; Growth; Growth Factor; Human; Immediate-Early Genes; Inositol; Knock-out; Laboratories; Learning; Link; Mediating; Membrane; Memory; Mental disorders; Metabotropic Glutamate Receptors; Molecular; Monitor; Morphology; Movement Disorders; Mus; Mutant Strains Mice; Neuraxis; Neuroglia; Neurologic; Neuronal Plasticity; Neurons; Nucleic Acid Regulatory Sequences; Pathway interactions; Pattern; Phase; Phenotype; Phosphotransferases; Play; Positioning Attribute; Process; Proline; Protein Binding; Protein Biosynthesis; Proteins; Purkinje Cells; Receptor Signaling; Recruitment Activity; Regulation; Relative (related person); Role; Second Messenger Systems; Serum Response Factor; Signal Pathway; Signal Transduction; Signal Transduction Pathway; Site; Small Interfering RNA; Synapses; Synaptic Transmission; Synaptic plasticity; System; Testing; Tilia; Transcription factor genes; base; computerized data processing; cost; depression; experience; extracellular; gain of function; inflammatory pain; insight; interdisciplinary approach; knock-down; loss of function; neuroregulation; neurotransmitter release; novel; postsynaptic; presynaptic; promoter; receptor; reconstitution; relating to nervous system; research study; response; second messenger; small hairpin RNA; success; synaptic function; synaptogenesis; therapy development; transcription factor; transmission process; tripolyphosphate

DESCRIPTION (provided by applicant): The 100 billion neurons in the human brain have an average of 10,000 synapses. By establishing a dynamic network of synaptic connections, the brain is able to attain the level of functional complexity that underlies human behavior. The efficiency of signal transmission at synapses is constantly being adapted in response to experience as encoded by neural activity. This synaptic plasticity is critical for the fine- tuning of brain development as well as higher brain function such as learning and memory. The plasticity of synapses is modulated and maintained by processes that are sensitive to neuronal activity and cell-cell contact. Trans-synaptic protein interactions induce differentiation of the synapse and regulate the morphology and function of synapses. Release of neurotransmitter regulates the activity of the neuron and activates a variety of second messenger pathways including calcium-signaling systems, which have a central role in regulating both rapid synaptic plasticity and long-term changes in synaptic connections through the activation of gene transcription. These activity-regulated genes then modulate the function of the neuron and can directly affect synapse function. The proposed Conte Center will investigate the inter- and intracellular signaling to and from the synapse that induce synapse formation and differentiation and regulate synaptic efficacy. These signal transduction pathways are initiated at sites of neuronal cell contact by extracellular signals and are then relayed to the nucleus and finally cycle back to the synapse to regulate synaptic function. The proposed Center brings together six leading laboratories in the study of synaptic function to take multiple interdisciplinary collaborative approaches to investigate the molecular mechanisms involved in regulating synaptic transmission and plasticity. Richard Huganir will be identifying molecules involved in the formation, differentiation and regulation of excitatory synapses in the brain. Paul Worley and Sol Snyder will be analyzing how macromolecular signaling complexes at excitatory synapses control neuronal calcium signaling and synaptic function. David Linden and David Ginty will be analyzing how calcium regulates neuronal transcription factors and gene expression. Dwight Bergles will be studying the interaction of glutamate transporters and metabotropic glutamate receptors and the role of this interaction in regulating synaptic function. All of these projects center on the synapse and address how extracellular and intracellular signals converge on the synapse to sculpt its morphology and function. Many neurological and psychiatric diseases result from defects in the development and/or function of synapses. Thus, understanding the mechanisms regulating the formation and modulation of synaptic transmission in the brain is critical for the development of treatments for these diseases.

DESCRIPTION (provided by applicant): The 100 billion neurons in the human brain have an average of 10,000 synapses. By establishing a dynamic network of synaptic connections, the brain is able to attain the level of functional complexity that underlies human behavior. The efficiency of signal transmission at synapses is constantly being adapted in response to experience as encoded by neural activity. This synaptic plasticity is critical for the fine- tuning of brain development as well as higher brain function such as learning and memory. The plasticity of synapses is modulated and maintained by processes that are sensitive to neuronal activity and cell-cell contact. Trans-synaptic protein interactions induce differentiation of the synapse and regulate the morphology and function of synapses. Release of neurotransmitter regulates the activity of the neuron and activates a variety of second messenger pathways including calcium-signaling systems, which have a central role in regulating both rapid synaptic plasticity and long-term changes in synaptic connections through the activation of gene transcription. These activity-regulated genes then modulate the function of the neuron and can directly affect synapse function. The proposed Conte Center will investigate the inter- and intracellular signaling to and from the synapse that induce synapse formation and differentiation and regulate synaptic efficacy. These signal transduction pathways are initiated at sites of neuronal cell contact by extracellular signals and are then relayed to the nucleus and finally cycle back to the synapse to regulate synaptic function. The proposed Center brings together six leading laboratories in the study of synaptic function to take multiple interdisciplinary collaborative approaches to investigate the molecular mechanisms involved in regulating synaptic transmission and plasticity. Richard Huganir will be identifying molecules involved in the formation, differentiation and regulation of excitatory synapses in the brain. Paul Worley and Sol Snyder will be analyzing how macromolecular signaling complexes at excitatory synapses control neuronal calcium signaling and synaptic function. David Linden and David Ginty will be analyzing how calcium regulates neuronal transcription factors and gene expression. Dwight Bergles will be studying the interaction of glutamate transporters and metabotropic glutamate receptors and the role of this interaction in regulating synaptic function. All of these projects center on the synapse and address how extracellular and intracellular signals converge on the synapse to sculpt its morphology and function. Many neurological and psychiatric diseases result from defects in the development and/or function of synapses. Thus, understanding the mechanisms regulating the formation and modulation of synaptic transmission in the brain is critical for the development of treatments for these diseases.