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MRS-measured glutamate versus GABA reflects excitatory versus inhibitory neural activities in awake mice
Journal of Cerebral Blood Flow & Metabolism ( IF 6.3 ) Pub Date : 2021-09-13 , DOI: 10.1177/0271678x211045449
Yuhei Takado 1 , Hiroyuki Takuwa 1 , Kazuaki Sampei 1 , Takuya Urushihata 1 , Manami Takahashi 1 , Masafumi Shimojo 1 , Shoko Uchida 1 , Nobuhiro Nitta 2 , Sayaka Shibata 2 , Keisuke Nagashima 3 , Yoshihiro Ochi 3 , Maiko Ono 1 , Jun Maeda 1 , Yutaka Tomita 4 , Naruhiko Sahara 1 , Jamie Near 5 , Ichio Aoki 2 , Kazuhisa Shibata 1, 6 , Makoto Higuchi 1
Affiliation  

To assess if magnetic resonance spectroscopy (MRS)-measured Glutamate (Glu) and GABA reflect excitatory and inhibitory neural activities, respectively, we conducted MRS measurements along with two-photon mesoscopic imaging of calcium signals in excitatory and inhibitory neurons of living, unanesthetized mice. For monitoring stimulus-driven activations of a brain region, MRS signals and mesoscopic neural activities were measured during two consecutive sessions of 15-min prolonged sensory stimulations. In the first session, putative excitatory neuronal activities were increased, while inhibitory neuronal activities remained at the baseline level. In the second half, while excitatory neuronal activities remained elevated, inhibitory neuronal activities were significantly enhanced. We assessed regional neurochemical statuses by measuring MRS signals, which were overall in accordance with the neural activities, and neuronal activities and neurochemical statuses in a mouse model of Dravet syndrome under resting condition. Mesoscopic assessments showed that activities of inhibitory neurons in the cortex were diminished relative to wild-type mice in contrast to spared activities of excitatory neurons. Consistent with these observations, the Dravet model exhibited lower concentrations of GABA than wild-type controls. Collectively, the current investigations demonstrate that MRS-measured Glu and GABA can reflect spontaneous and stimulated activities of neurons producing and releasing these neurotransmitters in an awake condition.



中文翻译:

MRS 测量的谷氨酸与 GABA 反映了清醒小鼠的兴奋性与抑制性神经活动

为了评估磁共振波谱 (MRS) 测量的谷氨酸 (Glu) 和 GABA 是否分别反映兴奋性和抑制性神经活动,我们进行了 MRS 测量以及活体未麻醉小鼠兴奋性和抑制性神经元中钙信号的双光子介观成像. 为了监测大脑区域的刺激驱动激活,在连续两次 15 分钟的长时间感觉刺激期间测量 MRS 信号和细观神经活动。在第一次会议中,假定的兴奋性神经元活动增加,而抑制性神经元活动保持在基线水平。下半年,虽然兴奋性神经元活动保持升高,但抑制性神经元活动显着增强。我们通过测量 MRS 信号来评估区域神经化学状态,总体与静息状态下Dravet综合征小鼠模型的神经活动、神经元活动和神经化学状态一致。细观评估表明,与野生型小鼠相比,皮质中抑制性神经元的活动减少了,而兴奋性神经元的活动则没有。与这些观察结果一致,Dravet 模型的 GABA 浓度低于野生型对照。总的来说,目前的研究表明,MRS 测量的 Glu 和 GABA 可以反映神经元在清醒状态下产生和释放这些神经递质的自发和受刺激活动。细观评估表明,与野生型小鼠相比,皮质中抑制性神经元的活动减少了,而兴奋性神经元的活动则没有。与这些观察结果一致,Dravet 模型的 GABA 浓度低于野生型对照。总的来说,目前的研究表明,MRS 测量的 Glu 和 GABA 可以反映神经元在清醒状态下产生和释放这些神经递质的自发和受刺激活动。细观评估表明,与野生型小鼠相比,皮质中抑制性神经元的活动减少了,而兴奋性神经元的活动则没有。与这些观察结果一致,Dravet 模型的 GABA 浓度低于野生型对照。总的来说,目前的研究表明,MRS 测量的 Glu 和 GABA 可以反映神经元在清醒状态下产生和释放这些神经递质的自发和受刺激活动。

更新日期:2021-09-13
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