Dynamic Balancing of Excitation and Inhiition During Gamma Oscillations

描述(由申请人提供)：目的：这项建议解决了在伽马振荡期间如何在皮质回路中维持兴奋和抑制之间的平衡。具体地说，我将确定在快速调制的伽马振荡中兴奋性和抑制性突触电流之间的关系。这项研究是在体内和体外的海马区进行的，使用细胞内和细胞外的电生理记录。背景：伽玛振荡，即神经元在20-80赫兹频率上的同步尖峰，被认为在感觉信息的处理中起着至关重要的作用。来自大脑皮层区域的活体记录显示，伽马振荡是由感觉刺激引起的。事实上，这些振荡的频率和幅度是由刺激的性质和注意轨迹来调节的。这些参与振荡的神经元的放电频率和数量的持续变化导致突触活动模式的快速变化。兴奋性和抑制性突触活动的平衡变化决定了皮层神经元执行的计算，并且是皮层网络稳定性的关键特征。然而，在这种快速调制的伽马振荡过程中，神经元的皮质网络如何在兴奋和抑制之间保持平衡尚不清楚。目的1：确定伽玛振荡幅度调制过程中兴奋电流与抑制电流的关系。利用在体内和体外的海马场和全细胞膜片钳同步记录，我将检验假设(I)：动态抑制电流 在调制伽马振荡幅度期间平衡励磁电流。目的2：确定伽玛振荡频率调制的潜在机制。利用在体内和体外的海马场和全细胞膜片钳同步记录，我将检验假设(II)：抑制性突触电流幅度的波动通过调节各个振荡周期之间的间隔来调制振荡频率。公共卫生相关性：通过建立抑制电路如何快速平衡兴奋变化，本研究将阐明使大脑皮层在广泛的兴奋刺激下稳健运行的机制。对调节皮质兴奋性的因素的深入了解可能有助于开发旨在预防皮质区域癫痫发生的治疗方法。

DESCRIPTION (provided by applicant): PURPOSE: This proposal addresses how a balance between excitation and inhibition is maintained in cortical circuits during gamma oscillations. Specifically, I will determine the relationship between excitatory and inhibitory synaptic currents during rapidly modulated gamma oscillations. This study is performed in the hippocampus both in vivo and in vitro, using intracellular and extracellular electrophysiological recordings. BACKGROUND: Gamma oscillations, the synchronous spiking of neurons at frequencies of 20-80Hz, are believed to play a crucial role in the processing of sensory information. In vivo recordings from cortical areas have shown that gamma oscillations are evoked by sensory stimuli. In fact, the frequency and amplitude of these oscillations are modulated by the nature of the stimulus and the locus of attention. These ongoing changes in the firing frequency and number of neurons participating in oscillations produce rapidly changing patterns of synaptic activity. Balanced changes in excitatory and inhibitory synaptic activity determine the computations performed by cortical neurons and are a critical characteristic of cortical network stability. It is not known, however, how cortical networks of neurons maintain a balance between excitation and inhibition during this rapidly modulated gamma oscillations. Aim 1: Determine the relationship between excitatory and inhibitory currents during the modulation of gamma oscillation amplitude. Using simultaneous field and whole cell patch-clamp recordings in the hippocampus both in vivo and in vitro, I will test the hypothesis (I) that: inhibitory currents dynamically balance excitatory currents during modulated gamma oscillation amplitude. Aim 2: Determine the mechanisms underlying the modulation of gamma oscillation frequency. Using simultaneous field and whole cell patch-clamp recordings in the hippocampus both in vivo and in vitro, I will test the hypothesis (II) that: fluctuations in the amplitude of inhibitory synaptic currents modulate oscillation frequency by regulating the interval between individual oscillation cycles. PUBLIC HEALTH RELAVANCE: By establishing how inhibitory circuits rapidly balance changes in excitation, this study will elucidate the mechanisms that enable the cortex to robustly operate over a broad range of excitatory stimuli. A deeper understanding of the factors that regulate cortical excitability may contribute to the development of therapies aimed at preventing epileptogensis in cortical areas.