Synchronization in Noisy, Heterogeneous Excitatory/Inhibitory Networks

嘈杂的异质兴奋/抑制网络中的同步

• 批准号: 9751977
• 负责人: Carmen Castro Canavier
• 金额: $ 42.01万
• 依托单位: LSU HEALTH SCIENCES CENTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-15 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9751977
• 关键词: Alzheimer' s Disease; Area; Attention; Biophysics; Brain; Cells; Closure by clamp; Code; Cognition; Cognitive Therapy; Cognitive deficits; Data; Dementia; Development; Dimensions; Disease; Epilepsy; Evolution; Exhibits; Feedback; Fire - disasters; Frequencies; Heterogeneity; Hippocampal Formation; Hippocampus (Brain); Hodgkin-Huxley model; In Vitro; Interneuron function; Interneurons; Kinetics; Lead; Light; Maps; Measures; Medial; Methods; Modeling; Mus; Myoepithelial cell; Neurons; Noise; Parvalbumins; Perception; Phase; Physiologic pulse; Physiological; Play; Population; Recurrence; Role; Scheme; Schizophrenia; Short Interspersed Nucleotide Elements; Signal Transduction; Slice; Stimulus; Synapses; Testing; Time; Work; base; cell cortex; design; entorhinal cortex; experimental study; improved; in vivo; memory encoding; memory retrieval; network models; novel; optogenetics; postsynaptic; stellate cell; support network; theories; transmission process; voltage; voltage clamp

Gamma band (30-90 Hz) oscillations are hypothesized to play an important role in normal cognition, including memory encoding and retrieval, attention and perception. Gamma synchrony is abnormally regulated in many disorders, such as epilepsy, schizophrenia and dementias such as Alzheimer's disease. Distinct mechanisms likely underlie gamma oscillations in different brain areas, and mechanisms may also vary within the same brain area under different conditions. Models of these diverse mechanisms generally assume that interneurons function as integrators that can fire at arbitrarily low rates (type 1 excitability). In contrast, resonator neurons have an abrupt threshold at a nonzero minimum firing frequency (type 2 excitability). We have previously shown that the fast spiking (FS), parvalbumin-positive (PV+) basket cell interneurons in the medial entorhinal cortex (MEC) are type 2, and exhibit strong resonance and post-inhibitory rebound (PIR). Moreover, our theo- retical work shows these features enhance the ability to synchronize in heterogeneous, sparsely-connected noisy networks. Aim 1 will focus on the biophysical basis for PIR and type 2 excitability in FS cells in mouse MEC and hippocampal area CA3 in vitro. Aim 2 will use models of CA3 and MEC FS cells from Aim 1 embed- ded in excitatory/inhibitory networks to develop new theory to identify and optimally manipulate the various mechanisms underlying gamma synchrony. We will analyze different slices of the parameter space to find or- ganizing principles for distinct gamma mechanisms and how to distinguish between them. We will develop the- oretical methods to account for the effect of jitter in spike times. This theory may lead to better design of poten- tial therapies for cognitive deficits. Aim 3 will test the theoretical predictions of optimally gated transitions into theta-nested gamma in the MEC in vitro using optogenetic control of extrinsic inputs. We will test the hypothe- ses that both excitatory and inhibitory theta-locked signals can evoke nested gamma oscillations during opto- genetically-induced theta in the MEC by aligning the phases of the FS interneurons. A consistent reset of the theta phase of gamma oscillations is required in many coding schemes; we expect that multiple reset mecha- nisms may be operative in the MEC. Our central hypothesis is that the excitability type of inhibitory interneu- rons controls the type and robustness of oscillations exhibited in excitatory/inhibitory networks.

假设伽马频段（30-90 Hz）振荡在正常认知中起着重要作用，包括 记忆编码和检索，注意力和感知。伽马同步在许多人中受到异常调节 疾病，例如癫痫，精神分裂症和痴呆症，例如阿尔茨海默氏病。不同的机制 不同大脑区域的伽马振荡可能是γ的基础，机制也可能在同一机制中有所不同 大脑区域在不同的条件下。这些不同机制的模型通常假定中间神经元 充当可以以任意较低速率（1型兴奋性）发射的集成剂。相反，谐振神经元 在非零的最小点火频率（2型兴奋性）下具有突然的阈值。我们以前有 显示快速峰值（FS），白蛋白阳性（PV+）篮细胞中间内侧的神经元 皮层（MEC）是2型，并且表现出强烈的共振和抑制后反弹（PIR）。而且，我们的theo- 恢复工作表明这些功能增强了在异质，稀疏连接中同步的能力 嘈杂的网络。 AIM 1将重点放在小鼠FS细胞中PIR和2型兴奋性的生物物理基础上 MEC和海马区域CA3体外。 AIM 2将使用AIM 1嵌入的CA3和MEC FS细胞的模型 在兴奋性/抑制网络中进行DED，以开发新理论，以识别和最佳操纵各种 伽马同步的基础机制。我们将分析参数空间的不同切片以查找或 为不同的伽马机制以及如何区分它们的原理。我们将发展 - 在尖峰时期抖动的效果的主题方法。该理论可能会导致更好的Poten-设计 认知缺陷的TIAL疗法。 AIM 3将测试最佳封闭过渡到达的理论预测 通过外在输入的光遗传学控制，在MEC体外，theta-nesta-nest gamma。我们将测试假设 兴奋性和抑制性theta锁定信号的SES在光学期间可以唤起嵌套的γ振荡 通过对齐FS中间神经元的相位，在MEC中遗传诱导的theta。一致的重置 在许多编码方案中，需要γ振荡的theta阶段。我们期望多个重置机制 - NISM在MEC中可能是操作的。我们的核心假设是抑制性间持续性的兴奋性类型 Rons控制兴奋性/抑制网络中表现出的振荡的类型和鲁棒性。