Synchronization in Noisy, Heterogeneous Excitatory/Inhibitory Networks

伽马波段（30-90 Hz）振荡被假设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。伽马同步在许多细胞中被异常调节， 疾病，如癫痫、精神分裂症和痴呆如阿尔茨海默病。不同的机制 可能是不同大脑区域伽马振荡的基础，并且机制也可能在同一区域内有所不同。 大脑在不同的条件下。这些不同机制的模型通常假设中间神经元 作为积分器的功能，可以以任意低的速率发射（1型兴奋性）。相反，共振神经元 在非零的最小激发频率下具有突变阈值（2型兴奋性）。我们先前已经 结果显示，内侧内嗅神经中的快速尖峰（FS）、小清蛋白阳性（PV+）篮状细胞中间神经元 皮层（MEC）是2型，并表现出强烈的共振和抑制后反弹（PIR）。此外，我们的Theo- 理论工作表明，这些功能增强了异构、稀疏连接网络中的同步能力。 噪声网络目的1探讨小鼠FS细胞PIR和2型兴奋性的生物物理基础 MEC和海马CA 3区。Aim 2将使用Aim 1中的CA 3和MEC FS细胞模型， 在兴奋性/抑制性网络发展新的理论，以确定和最佳地操纵各种 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- 理论方法来解释尖峰时间抖动的影响。这一理论可能会导致更好的设计潜力- 认知缺陷的临床治疗目标3将测试最佳门控跃迁到 在体外MEC中使用外部输入的光遗传学控制的θ-嵌套γ。我们会测试皮下组织- 认为兴奋性和抑制性θ锁定信号都可以在光周期中引起嵌套的γ振荡， 通过对齐FS中间神经元的相位，在MEC中遗传诱导θ。一个一致的重置 在许多编码方案中需要伽马振荡的θ相位;我们期望多个复位机制， nisms可以在MEC中起作用。我们的中心假设是，抑制性神经元的兴奋性类型- RON控制在兴奋/抑制网络中表现出的振荡的类型和鲁棒性。

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.