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.

假设伽马带（30-90 Hz）振荡在正常认知中发挥重要作用，包括 记忆编码和检索、注意力和感知。伽马同步在许多方面受到异常调节 疾病，例如癫痫、精神分裂症和痴呆症（例如阿尔茨海默病）。独特的机制 可能是不同大脑区域的伽马振荡的基础，并且同一区域内的机制也可能有所不同 不同条件下的大脑区域。这些不同机制的模型通常假设中间神经元 充当积分器，可以以任意低的速率激发（1 型兴奋性）。相反，谐振神经元 在非零最小放电频率处有一个突然的阈值（2 类兴奋性）。我们之前有过 研究表明，内侧内嗅神经元中的快速尖峰（FS）、小清蛋白阳性（PV+）篮状细胞中间神经元 皮层 (MEC) 属于 2 型，表现出强烈的共振和抑制后反弹 (PIR)。此外，我们的理论—— 实际工作表明这些功能增强了异构、稀疏连接中的同步能力 嘈杂的网络。目标 1 将重点关注小鼠 FS 细胞 PIR 和 2 型兴奋性的生物物理基础 MEC 和海马区 CA3 体外。目标 2 将使用目标 1 嵌入的 CA3 和 MEC FS 细胞模型 致力于兴奋/抑制网络开发新理论来识别和最佳地操纵各种 伽马同步的机制。我们将分析参数空间的不同部分来找到或- 不同伽马机制的组织原理以及如何区分它们。我们将开发- 解释尖峰时间抖动影响的理论方法。该理论可能会导致更好的潜在设计 认知缺陷的初步治疗。目标 3 将测试最优门控转换的理论预测 使用外部输入的光遗传学控制，在体外 MEC 中进行 theta 嵌套伽玛。我们将测试假设 认为兴奋性和抑制性 θ 锁定信号都可以在光电过程中引起嵌套伽马振荡 通过调整 FS 中间神经元的相位，在 MEC 中遗传诱导 theta。一致的重置 许多编码方案都需要伽马振荡的 theta 相位；我们期望多次重置机械 主义可能在 MEC 中发挥作用。我们的中心假设是抑制性间质的兴奋性类型 rons 控制兴奋/抑制网络中振荡的类型和鲁棒性。