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一种研究海马脑切片中相干γ 波段振荡的新方法。

A Novel Approach to Study Coherent γ-Band Oscillations in Hippocampal Brain Sections.

机构信息

Neuroscience Graduate Program, University of Michigan Medical School, Ann Arbor, 48109 MI.

Department of Pharmacology, University of Michigan Medical School, Ann Arbor, 48109 MI.

出版信息

eNeuro. 2023 Jul 24;10(7). doi: 10.1523/ENEURO.0167-23.2023. Print 2023 Jul.

Abstract

γ-Band oscillations (GBOs) are generated by fast-spiking interneurons (FSIs) and are critical for cognitive functions. Abnormalities in GBOs are frequently observed in schizophrenia and bipolar disorder and are strongly correlated with cognitive impairment. However, the underlying mechanisms are poorly understood. Studying GBOs in preparations is challenging because of high energy demands and the need for continuous oxygen delivery to the tissue. As a result, GBOs are typically studied in brain tissue from very young animals or in experimental setups that maximize oxygen supply but compromise spatial resolution. Thus, there is a limited understanding of how GBOs interact within and between different brain structures and in brain tissue from mature animals. To address these limitations, we have developed a novel approach for studying GBOs in hippocampal slices from mature animals, using 60-channel, perforated microelectrode arrays (pMEAs). pMEAs enhance oxygen delivery and increase spatial resolution in electrophysiological recordings, enabling comprehensive analyses of GBO synchronization within discrete brain structures. We found that transecting the Schaffer collaterals, a neural pathway within the hippocampus, impairs GBO coherence between CA1 and CA3 subfields. Furthermore, we validated our approach by studying GBO coherence in an mutant mouse model exhibiting inhibitory synaptic dysfunction. We discovered that GBO coherence remains intact in the CA3 subfield of these mutant mice but is impaired within and between the CA1 subfield. Overall, our approach offers significant potential to characterize GBOs in brain sections of animal models, enhancing our understanding of network dysfunction in psychiatric disorders.

摘要

γ-波段振荡(GBOs)由快速放电中间神经元(FSIs)产生,对认知功能至关重要。精神分裂症和双相情感障碍中经常观察到 GBO 异常,并且与认知障碍密切相关。然而,其潜在机制尚不清楚。由于能量需求高,并且需要持续向组织供氧,因此在 制剂中研究 GBO 具有挑战性。结果,GBOs 通常在非常年幼的动物的脑组织中或在最大限度地供应氧气但损害空间分辨率的实验设置中进行研究。因此,对于 GBO 如何在不同脑结构内和之间以及在成熟动物的脑组织中相互作用,我们的理解有限。为了解决这些限制,我们开发了一种从成熟动物的海马切片中研究 GBO 的新方法,使用 60 通道穿孔微电极阵列(pMEA)。pMEA 增强了氧气输送并提高了电生理记录的空间分辨率,从而能够全面分析离散脑结构内的 GBO 同步。我们发现,横切海马内的神经通路 Schaffer 侧支会损害 CA1 和 CA3 亚区之间的 GBO 相干性。此外,我们通过研究在表现出抑制性突触功能障碍的 突变体小鼠模型中 GBO 相干性来验证我们的方法。我们发现,这些突变体小鼠的 CA3 亚区中的 GBO 相干性保持完整,但 CA1 亚区中的 GBO 相干性受损。总体而言,我们的方法为在动物模型的 脑切片中表征 GBO 提供了重要潜力,增强了我们对精神疾病中网络功能障碍的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f654/10368148/57fa1120efd0/ENEURO.0167-23.2023_f001.jpg

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