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Relationship between oxygen consumption and neuronal activity in a defined neural circuit.
BMC Biology ( IF 5.4 ) Pub Date : 2020-07-03 , DOI: 10.1186/s12915-020-00811-6
Suzan Özugur 1, 2 , Lars Kunz 1 , Hans Straka 1
Affiliation  

Neuronal computations related to sensory and motor activity along with the maintenance of spike discharge, synaptic transmission, and associated housekeeping are energetically demanding. The most efficient metabolic process to provide large amounts of energy equivalents is oxidative phosphorylation and thus dependent on O2 consumption. Therefore, O2 levels in the brain are a critical parameter that influences neuronal function. Measurements of O2 consumption have been used to estimate the cost of neuronal activity; however, exploring these metabolic relationships in vivo and under defined experimental conditions has been limited by technical challenges. We used isolated preparations of Xenopus laevis tadpoles to perform a quantitative analysis of O2 levels in the brain under in vivo-like conditions. We measured O2 concentrations in the hindbrain in relation to the spike discharge of the superior oblique eye muscle-innervating trochlear nerve as proxy for central nervous activity. In air-saturated bath Ringer solution, O2 levels in the fourth ventricle and adjacent, functionally intact hindbrain were close to zero. Inhibition of mitochondrial activity with potassium cyanide or fixation of the tissue with ethanol raised the ventricular O2 concentration to bath levels, indicating that the brain tissue consumed the available O2. Gradually increasing oxygenation of the Ringer solution caused a concurrent increase of ventricular O2 concentrations. Blocking spike discharge with the local anesthetics tricaine methanesulfonate diminished the O2 consumption by ~ 50%, illustrating the substantial O2 amount related to neuronal activity. In contrast, episodes of spontaneous trochlear nerve spike bursts were accompanied by transient increases of the O2 consumption with parameters that correlated with burst magnitude and duration. Controlled experimental manipulations of both the O2 level as well as the neuronal activity under in vivo-like conditions allowed to quantitatively relate spike discharge magnitudes in a particular neuronal circuitry with the O2 consumption in this area. Moreover, the possibility to distinctly manipulate various functional parameters will yield more insight in the coupling between metabolic and neuronal activity. Thus, apart from providing quantitative empiric evidence for the link between physiologically relevant spontaneous spike discharge in the brain and O2-dependent metabolism, isolated amphibian preparations are promising model systems to further dissociate the O2 dynamics in relation to neuronal computations.

中文翻译:

特定神经回路中耗氧量与神经元活动之间的关系。

与感觉和运动活动相关的神经元计算以及尖峰放电的维持、突触传递和相关的内务处理都需要大量的能量。提供大量能量当量的最有效的代谢过程是氧化磷酸化,因此依赖于氧气消耗。因此,大脑中的氧气水平是影响神经元功能的关键参数。氧气消耗量的测量已被用来估计神经元活动的成本;然而,在体内和特定实验条件下探索这些代谢关系受到技术挑战的限制。我们使用非洲爪蟾蝌蚪的分离制剂在体内类似条件下对大脑中的 O2 水平进行定量分析。我们测量了后脑中的 O2 浓度与支配上斜眼肌的滑车神经的尖峰放电的关系,作为中枢神经活动的代表。在空气饱和的林格溶液中,第四脑室和邻近的、功能完整的后脑中的氧气水平接近于零。用氰化钾抑制线粒体活性或用乙醇固定组织可将心室 O2 浓度升高至水浴水平,表明脑组织消耗了可用的 O2。逐渐增加林格溶液的氧合导致心室 O2 浓度同时增加。用局部麻醉剂甲磺酸三卡因阻断尖峰放电可使 O2 消耗量减少约 50%,说明大量 O2 量与神经元活动相关。相反,自发滑车神经尖峰爆发的发作伴随着氧气消耗的短暂增加,其参数与爆发强度和持续时间相关。在类体内条件下对 O2 水平和神经元活动进行受控实验操作,可以定量地将特定神经元回路中的尖峰放电幅度与该区域的 O2 消耗量联系起来。此外,明确操纵各种功能参数的可能性将使我们对代谢和神经元活动之间的耦合产生更多的了解。因此,除了为大脑中生理相关的自发尖峰放电与 O2 依赖性代谢之间的联系提供定量经验证据外,分离的两栖动物制剂也是有前途的模型系统,可以进一步分离与神经元计算相关的 O2 动力学。
更新日期:2020-07-03
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