School of Psychology and Neuroscience@Nottingham, University of Nottingham, Nottingham, UK.
Hippocampus. 2020 Oct;30(10):1021-1043. doi: 10.1002/hipo.23212. Epub 2020 May 12.
Reduced inhibitory GABA function, so-called neural disinhibition, has been implicated in cognitive disorders, including schizophrenia and age-related cognitive decline. We previously showed in rats that hippocampal disinhibition by local microinfusion of the GABA-A receptor antagonist picrotoxin disrupted memory and attention and enhanced hippocampal multi-unit burst firing recorded around the infusion site under isoflurane anesthesia. Here, we analyzed the hippocampal local field potential (LFP) recorded alongside the multi-unit data. We predicted frequency-specific LFP changes, based on previous studies implicating GABA in hippocampal oscillations, with the weight of evidence suggesting that disinhibition would facilitate theta and disrupt gamma oscillations. Using a new semi-automated method based on the kurtosis of the LFP peak-amplitude distribution as well as on amplitude envelope thresholding, we separated three distinct hippocampal LFP states under isoflurane anesthesia: "burst" and "suppression" states-high-amplitude LFP spike bursts and the interspersed low-amplitudeperiods-and a medium-amplitude "continuous" state. The burst state showed greater overall power than suppression and continuous states and higher relative delta/theta power, but lower relative beta/gamma power. The burst state also showed reduced functional connectivity across the hippocampal recording area, especially around theta and beta frequencies. Overall neuronal firing was higher in the burst than the other two states, whereas the proportion of burst firing was higher in burst and continuous states than the suppression state. Disinhibition caused state- and frequency-dependent LFP changes, tending to increase power at lower frequencies (<20 Hz), but to decrease power and connectivity at higher frequencies (>20 Hz) in burst and suppression states. The disinhibition-induced enhancement of multi-unit bursting was also state-dependent, tending to be more pronounced in burst and suppression states than the continuous state. Overall, we characterized three distinct hippocampal LFP states in isoflurane-anesthetized rats. Disinhibition changed hippocampal LFP oscillations in a state- and frequency-dependent way. Moreover, the disinhibition-induced enhancement of multi-unit bursting was also LFP state-dependent.
抑制性 GABA 功能减弱，即所谓的神经去抑制，与认知障碍有关，包括精神分裂症和与年龄相关的认知能力下降。我们之前在大鼠中表明，通过局部微量输注 GABA-A 受体拮抗剂荷包牡丹碱引起的海马去抑制，会破坏记忆和注意力，并在异氟烷麻醉下增强记录到的输注部位周围的海马多单位爆发放电。在这里，我们分析了与多单位数据一起记录的海马局部场电位 (LFP)。我们根据先前的研究表明 GABA 参与了海马振荡，预测了 LFP 的频率特异性变化，有证据表明去抑制会促进θ波并破坏γ波振荡。使用一种基于 LFP 峰幅度分布峰度以及幅度包络阈值的新半自动方法，我们在异氟烷麻醉下将海马 LFP 分为三种不同的状态：“爆发”和“抑制”状态——高幅度 LFP 尖峰爆发和穿插的低幅度周期——以及中幅度“连续”状态。爆发状态的总体功率大于抑制和连续状态，相对 delta/theta 功率更高，但相对 beta/gamma 功率更低。爆发状态还显示出跨海马记录区域的功能连接减少，尤其是在 theta 和 beta 频率周围。爆发状态的整体神经元放电高于其他两种状态，而爆发和连续状态的爆发放电比例高于抑制状态。去抑制引起状态和频率依赖性的 LFP 变化，倾向于增加较低频率（<20 Hz）的功率，但在爆发和抑制状态下降低较高频率（>20 Hz）的功率和连接性。多单位爆发的去抑制诱导增强也依赖于状态，在爆发和抑制状态下比连续状态下更为明显。总的来说，我们在异氟烷麻醉的大鼠中描述了三种不同的海马 LFP 状态。去抑制以状态和频率依赖性的方式改变海马 LFP 振荡。此外，多单位爆发的去抑制诱导增强也依赖于 LFP 状态。
