Linking Synaptic Properties to Neural Network Operation

将突触属性与神经网络操作联系起来

• 批准号: 7255516
• 负责人: Kevin J. Staley
• 金额: $ 38.37万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-09-30 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7255516
• 关键词: Adenosine; Adenosine A1 Receptor; Affect; Area; Behavior; Biological Assay; Biological Neural Networks; Calcium; Chromosome Pairing; Condition; Data; Electroencephalography; Epilepsy; Epileptogenesis; Future; Goals; Grant; Hippocampus (Brain); In Vitro; Individual; Investigation; Length; Link; Long-Term Depression; Long-Term Potentiation; Measures; Mediating; Membrane; Mental Depression; N-Methyl-D-Aspartate Receptors; N-Methylaspartate; NMDA receptor antagonist; Neurons; Operative Surgical Procedures; Pattern; Potassium Channel; Preparation; Probability; Property; Pyramidal Cells; Rate; Recovery; Recurrence; Seizures; Signal Transduction; Slice; Synapses; Synaptic plasticity; Test Result; Testing; Time; Whole-Cell Recordings; Withdrawal; Work; base; improved; postsynaptic; presynaptic; programs; receptor; recurrent depression; response; synaptic depression

DESCRIPTION (provided by applicant): The goal of this proposal is to understand the interactions between the activity of a neural network and the properties of the synapses that link the individual neurons. The rationale for the proposed studies is based on several discoveries made during the last grant cycle. In area CA3 of the disinhibited hippocampal slice preparation, bursts of network activity are possible when there is sufficient strength of the recurrent collateral synapses that link the pyramidal cell in this area. Thus short-term, activity-dependent depression of the strength of these synapases terminates bursts, and recovery from this short-term depression determines when the next burst is possible. Further, long-term determinants of the strength of these synapses also affect burst probability, so that both long-term potentiation (LTP) and long-term depression (LTD) produce corresponding long-term changes in burst timing. Under the appropriate conditions, burst activity can induce either LTP or LTD. In the case of LTD, the changes in strength are stabilized by an associated change in the threshold for further LTP or LTD induction. In the next cycle we propose to test two hypotheses related to these findings. First, one component of short-term synaptic depression in CA3 appears to be mediated by dendritic calcium influx. We will test the hypothesis that adenosine acting at presynaptic A1 receptors mediates this unusual mechanism of short-term depression. Second, we will investigate the mechanism by which the threshold for long-term synaptic plasticity is altered in CA3. We will test the hypothesis that a reduction in the maximum NMDA receptor-mediated postsynaptic calcium influx is associated with LTD. Finally, we will test how these relationships between synaptic properties and network behavior may affect epileptogenesis and the treatment of seizures. These investigations will help us understand what determines the timing of interictal epileptic activity, which is needed in order to use the temporal pattern of interictal activity to predict the probability of future seizures. In addition, these investigations will help us understand how to produce stable, long-term decreases in the probability of seizures by selective induction of LTD at the most active synapses in epileptic foci.

描述（由申请人提供）：本提案的目标是了解神经网络活动与连接单个神经元的突触特性之间的相互作用。拟议研究的基本原理是基于在上一个拨款周期中取得的几项发现。在去抑制海马切片准备的CA3区，当连接该区域锥体细胞的循环侧突触有足够的强度时，网络活动的爆发是可能的。因此，这些突触强度的短期、活动依赖性抑制终止了爆发，而这种短期抑制的恢复决定了下一次爆发的可能。此外，这些突触强度的长期决定因素也会影响突发概率，因此长期增强（LTP）和长期抑制（LTD）都会产生相应的突发时间的长期变化。在适当的条件下，突发活动可以诱发LTP或LTD。在LTD的情况下，强度的变化通过进一步LTP或LTD诱导的阈值的相关变化来稳定。