Excitatory and Inhibitory Synaptic Connectivity in Posttraumatic Epileptogenesis

创伤后癫痫发生中的兴奋性和抑制性突触连接

• 批准号: 7835543
• 负责人: XIAOMING JIN
• 金额: $ 24.9万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-15 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7835543
• 关键词: Address; Antiepileptic Agents; Axon; Brain; Brain Injuries; Chronic; Confocal Microscopy; Coupling; Development; Epilepsy; Epileptogenesis; Exhibits; Frequencies; Genes; Image; In Vitro; Injury; Knockout Mice; Lasers; Lesion; Measures; Modeling; Mus; Neocortex; Neurons; Play; Prevention therapy; Proteins; Pyramidal Cells; Research Proposals; Role; Scanning; Slice; Synapses; Synaptic Transmission; Techniques; Time; Transfection; Transgenic Mice; Traumatic Brain Injury; Whole-Cell Recordings; axonal sprouting; base; gene gun; hippocampal pyramidal neuron; improved; in vitro Model; in vivo; insight; neocortical; neural circuit; novel; presynaptic; prevent; research study; somatosensory

Trauniatic brain injury often results in epilepsy that is poorly controlled by antiepileptic drugs. Although there is evitjence that axonal sproutingvenhanced excitatory synaptic connectivity and reduced inhibitory synaptic tranismisision are associated with posttraurriatic epileptogenesis, further information on how these changes occur and contribute to epileptogenesis is inconriplete. This information is crut^ial in providing a rational basis for the development of new therapies aimed to disrupt posttraumatic epileptogenesis. in the jai-pposed;study, I will use the partial cortical isolation ("undercut") niodel and,a novel prganotypic slice culture model of posttraumatic epileptogenesis to investigate alterations in excitatory and inhibitory synaptic connectivity, Three specific questions will be addressed: (1) Does axonal sprouting play a critical role in posttraumatic epileptogienesis? (2) is there an incfeaise in excitatory synaptic coupling; between layer V pyramidal neurons after a chronic partial cortical isolation? I will use a combination of single and paired vvhole ceil recording, laser scanning photostimulation (LSP), transgenic mice, organotypic brain slice culture, gene gun transfectibn, and time-lapse confocal microscopy techniques. An LSP-guided dual whole cell recording tiechiiit^ue will be developed to improve efficiency of paired recordings. The resiilts of these experiments will identify and characterize alterations in excitatory synaptic transmission in the epileptogenic neocortex, document morphological dynamics during axonal sprouting after traumatic brain injury, and establish a novel in vitro model of posttraumatic epileptogenesis. Results from the pi'bposed study will contribute to a further understanding of normal synaptic circuitry and pathological ciianges involved in posttraumatic epilepsy and provide insights for- development of noveltherapies for preventing epileptogenesis after brain trauma.

创伤性脑损伤常导致癫痫，抗癫痫药物控制不佳。虽然