Dynamic Balancing of Excitation and Inhiition During Gamma Oscillations

描述（由申请人提供）：目的：本提案解决了伽马振荡期间皮层回路中如何维持兴奋和抑制之间的平衡。具体来说，我将确定在快速调制伽马振荡期间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中进行的，使用细胞内和细胞外的电生理记录。背景：伽马振荡，即神经元在20-80Hz频率上的同步峰值，被认为在感觉信息的处理中起着至关重要的作用。来自皮层区域的体内记录显示，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力的轨迹调节的。这些放电频率和参与振荡的神经元数量的持续变化产生了快速变化的突触活动模式。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，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中，神经元皮层网络如何维持兴奋和抑制之间的平衡尚不清楚。目的1：确定伽马振荡振幅调制过程中兴奋电流和抑制电流之间的关系。在体内和体外，我将使用海马体同时场和全细胞膜片钳记录，验证假设(1)：动态抑制电流

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.