Rapid homeostatic plasticity of excitation-inhibition balance in thalamocortical microcircuits

大脑中神经元之间的兴奋性和抑制性连接通过以下方式不断完善： 体验.为了避免过度或过低的兴奋性，稳态过程确保神经元的放电率是正常的。 在扰动之后返回适当的设定点。一个重要的方法是保存适当的神经元 放电率是通过回路内兴奋-抑制平衡（E/I平衡）的稳态调节。 在体内，只有缓慢的细胞自主稳态过程被确定，但研究表明，更快， 补偿机制是必要的，以维持稳定的放电，面对快速变化，从赫布 可塑性理论和实验证据表明，E/I的动态平衡是必要的， 网络，以保持稳定性，但这一过程从来没有在体内得到证明。 丘脑皮层（TC）轴突将视觉感觉信息发送到初级视皮层，初级视皮层主要 终止于新皮质层4（L4）。TC轴突直接兴奋星星锥体（SP）神经元和PV+快速发放 (FS)中间神经元FS中间神经元然后提供对SP神经元的双突触前馈抑制。 Turrigiano实验室的初步数据表明，丘脑皮层前馈E/I比SP neurons神经元is dynamically动态maintained维持.有趣的是，L4 SP神经元的平均放电率（分钟至小时）， 视觉皮层在不同的环境或昼夜节律状态下并不不同。我假设SP神经元放电 通过调整激励强度以匹配前馈的强度 在不同层次的感觉驱动中产生抑制。我将使用两种范例在体内对此进行测试：i） 单眼视觉剥夺（MD）和ii）使用DREADD调制PV+ FS放电率。中的每 在这些范例中，我将使用慢性电极植入物在体内记录L4中FS和SP神经元的放电速率， 并准备皮层切片以探测每种突触类型的突触特性变化。 我希望这些实验能够阐明神经元放电率的基本原理， 在体内调节。如果成功的话，这将使我们对神经元稳态的理解超越缓慢的 细胞自主过程，并揭示快速，潜在的网络水平的机制，稳定神经元 在较短的时间尺度上的发射率。

The excitatory and inhibitory connections between neurons in the brain are continually refined through experience. To avoid hyper- or hypo excitability, homeostatic processes ensure that neuronal firing rates are returned an appropriate set-point after perturbation. One important way to preserve appropriate neuronal firing rates is through homeostatic regulation of the excitation-inhibition balance (E/I balance) within a circuit. Only slow cell-autonomous homeostatic processes been identified in vivo, but studies suggest that more rapid compensatory mechanisms are necessary to maintain stable firing in the face of rapid changes from Hebbian plasticity. Theoretical and experimental evidence suggests that dynamic balancing of E/I is necessary for networks to maintain stability, but this process has never been demonstrated in vivo. Thalamocortical (TC) axons send visual sensory information to the primary visual cortex, which mainly terminate in neocortical layer 4 (L4). TC axons directly excite star pyramidal (SP) neurons and PV+ fast-spiking (FS) interneurons. FS interneurons then provide disynaptic feedforward inhibition onto SP neurons. Preliminary data from the Turrigiano lab indicates that the thalamocortical feedforward E/I ratio to SP neurons is dynamically maintained. Interestingly, average firing rates (minutes to hours) of L4 SP neurons in visual cortex are not different across environmental or circadian states. I hypothesize that SP neuron firing rates are dynamically stabilized by scaling the strength of excitation to match the strength of feedforward inhibition across vastly different levels of sensory drive. I will test this in vivo using two paradigms: i) monocular visual deprivation (MD) and ii) modulation of PV+ FS firing rates using DREADDs. For each of these paradigms, I will record firing rates of FS and SP neurons in L4 in vivo using chronic electrode implants, and prepare cortical slices to probe for changes in synaptic properties at each synapse type. I expect that these experiments will elucidate basic principles about how neuronal firing rates are regulated in vivo. If successful, this would extend our understanding of neuronal homeostasis beyond slow cell-autonomous processes and reveal rapid, potentially network-level mechanisms that stabilize neuronal firing rates on shorter timescales.