Synchronization in Noisy, Heterogeneous Excitatory/Inhibitory Networks

伽马频段(30-90赫兹)振荡被认为在正常认知中发挥重要作用，包括 记忆编码和提取、注意力和知觉。伽马同步在许多情况下都是异常调节的 疾病，如癫痫、精神分裂症和痴呆症，如阿尔茨海默病。不同的机制 可能是不同脑区伽马振荡的基础，机制也可能在相同的区域内有所不同 不同条件下的脑区。这些不同机制的模型通常假设中间神经元 起积分器的作用，可以以任意低的频率(类型1兴奋性)触发。相比之下，共振器神经元 在非零的最小激发频率下有一个突然的阈值(第二类兴奋性)。我们之前已经 结果显示，内侧内嗅区的快峰(FS)、小白蛋白阳性(PV)篮状细胞间神经元 大脑皮层(MEC)为2型，表现出强烈的共振和抑制后反弹(PIR)。此外，我们的理论- 理论工作表明，这些功能增强了在异类、稀疏连接中进行同步的能力 嘈杂的网络。目标1将重点介绍小鼠FS细胞PIR和2型兴奋性的生物物理基础 MEC和体外培养的海马区CA3。AIM 2将使用AIM 1中嵌入的CA3和MEC FS细胞模型- DED在兴奋/抑制网络中开发新的理论来识别和优化操纵各种 伽马同步的潜在机制。我们将分析参数空间的不同切片以找到或- 不同伽马机制的组织原则以及如何区分它们。我们会发展- 解释尖峰时间抖动影响的理论方法。这一理论可能会导致更好的潜水设计- 治疗认知缺陷的军事疗法。目标3将测试最佳选通跃迁到 在体外利用光基因控制外在输入的MEC中的Theta嵌套伽马。我们将测试假说- SES认为，兴奋性和抑制性theta锁定信号都可以在光诱导过程中引起嵌套的伽马振荡。 通过排列FS中间神经元的相位，在MEC中通过基因诱导的theta。一致的重置 在许多编码方案中需要伽马振荡的Theta相；我们预计多个重置机制- NISMS可能在MEC中起作用。我们的中心假设是抑制性中枢神经元的兴奋性类型- RONS控制兴奋/抑制网络中表现出的振荡的类型和稳健性。

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.