Cellular Mechanisms in Epileptogenesis

癫痫发生的细胞机制

基本信息

批准号：
8500465
负责人：
John R Huguenard
金额：
$ 33.23万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1978
资助国家：
美国
起止时间：
1978-01-01 至 2014-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8500465
关键词：
Absence Epilepsy Action Potentials Address Affect Agonist Antiepileptic Agents Axon Benzodiazepines Bilateral Binding Biosensor Brain Brain region Cell Nucleus Cells Chronic Data Dependence Diazepam Binding Inhibitor Dorsal Electroencephalography Ensure Epilepsy Epileptogenesis Event Excitatory Synapse Fiber Flumazenil Focal Seizure Frequencies GABA Receptor Generalized Epilepsy Generations Glial Fibrillary Acidic Protein Goals Grant Image In Vitro Individual Infarction Infusion procedures Injury Kinetics Knockout Mice Knowledge Ligands Measures Mediating Memory Modeling Mouse Strains Mus Neuraxis Neurobiology Neuroglia Neurons Neuropeptides Partial Epilepsies Pathway interactions Pharmacology Physiologic pulse Play Predisposition Presynaptic Terminals Probability Process Property Protocols documentation Rattus Recovery Regulation Regulatory Pathway Relative (related person)Research Role Seizures Sensory Process Siblings Signal Transduction Site Sleep Slice Source Status Epilepticus Stimulus Structure Structure of nucleus infundibularis hypothalami Substantia nigra structure Synapses Testing Tetrodotoxin Thalamic structure Thrombospondin 1 Time Training Translating density design fluorocitrate gabapentin immunoreactivity in vivo induced pluripotent stem cell inhibitory neuron injured neglect neural circuit neurofilament neurosteroids nucleus reticularis overexpression pars compacta pituitary adenylate cyclase activating polypeptide public health relevance receptor receptor function research study response somatosensory synaptic inhibition synaptogenesis thrombospondin 2 ward

项目摘要

DESCRIPTION (provided by applicant): The thalamus is a subcortical structure that is widely interconnected with cortical circuits and plays a critical role in such vital and diverse brain functions as processing of sensory information, sleep and memory. Disruptions in thalamic structure and function are implicated in both generalized and focal epilepsies, yet certain aspects of thalamic function may serve to constrain epileptiform activity. Our preliminary results suggest mechanisms through which thalamic circuits provide activity-dependent adaptive and maladaptive changes that suppress or enhance epileptogenesis, respectively. In particular, cortical infarction or generation of focal cortical epileptiform activity leads to maladaptive increases in thalamic network connectivity and function that would enhance epileptogenesis. By contrast, multiple lines of evidence suggest that endogenous ligands for the benzodiazepine site of inhibitory GABA receptors, endozepines, are constitutively expressed in the thalamus to augment synaptic inhibition specifically in the thalamic reticular nucleus, a site proposed to underlie a key seizure regulatory pathway. In addition, the endozepine effects appear to be increased by experimental absence seizures, and act to blunt seizure intensity and duration. The proposed experiments will employ anatomical and electrophysiological approaches to analyze each mechanism individually in addition to their interactions, with the long term goal of providing an integrated view of adaptive and maladaptive processes important in the roles of this key brain structure in normal brain function and epilepsy.

描述（由申请人提供）：丘脑是一种皮层结构，与皮质回路广泛互连，并且在处理感官信息，睡眠和记忆等重要和多样化的大脑功能中起着至关重要的作用。丘脑结构和功能的破坏都与广义和局灶性癫痫发作有关，但是丘脑功能的某些方面可能有助于抑制癫痫样活性。我们的初步结果表明，丘脑回路通过这些机制提供了活性依赖性的适应性和适应不良的变化，可分别抑制或增强癫痫发生。特别是，皮质梗塞或局灶性皮质癫痫活性的产生会导致丘脑网络连通性和功能的适应不良，从而增强癫痫生成。相比之下，多种证据表明，抑制性GABA受体的苯二氮卓位点的内源配体在丘脑中的组成型表达，以在丘脑网状核中特异性增强突触抑制作用，该位点提出了一个孔子的隔离率，该站点提出了一个钥匙扣除率。此外，渗透率似乎通过癫痫发作而增加，并起到钝性癫痫发作强度和持续时间的作用。提出的实验将采用解剖学和电生理方法除了它们的相互作用外分析每个机制，其长期目标是提供适应性和适应不良过程的综合视图，这在这种关键大脑在正常大脑功能和癫痫中的关键作用中很重要。

项目成果

期刊论文数量（13）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Differential ontogenesis of presynaptic and postsynaptic GABAB inhibition in rat somatosensory cortex.

大鼠体感皮层突触前和突触后 GABAB 抑制的差异个体发生。

DOI：
10.1152/jn.1993.70.1.448
发表时间：
1993
期刊：
Journal of neurophysiology
影响因子：
2.5
作者：
Fukuda,A;Mody,I;Prince,DA
通讯作者：
Prince,DA

Afterpotential generation in hippocampal pyramidal cells.

DOI：
10.1152/jn.1981.45.1.86
发表时间：
1981
期刊：
Journal of neurophysiology
影响因子：
2.5
作者：
R. Wong;D. Prince
通讯作者：
R. Wong;D. Prince

Carbon dioxide sensitivity of dye coupling among glia and neurons of the neocortex.

新皮质神经胶质细胞和神经元之间染料耦合的二氧化碳敏感性。

DOI：
10.1523/jneurosci.04-05-01324.1984
发表时间：
1984
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
0
作者：
Connors,BW;Benardo,LS;Prince,DA
通讯作者：
Prince,DA

Heterogeneous axonal arborizations of rat thalamic reticular neurons in the ventrobasal nucleus.

腹基底核中大鼠丘脑网状神经元的异质轴突树枝化。