MRS-measured glutamate versus GABA reflects excitatory versus inhibitory neural activities in awake mice

MRS-measured glutamate versus GABA reflects excitatory versus inhibitory neural activities in awake mice
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DOI:
10.1177/0271678x211045449
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发表时间:
2020-10
影响因子:
6.3
通讯作者:
Y. Takado;H. Takuwa;Kazuaki Sampei;Takuya Urushihata;Manami Takahashi;Masafumi Shimojo;S. Uchida;Nobuhiro Nitta;S. Shibata;K. Nagashima;Yoshihiro Ochi;M. Ono;J. Maeda;Y. Tomita;N. Sahara;J. Near;I. Aoki;Kazuhisa Shibata;M. Higuchi
Y. Takado;H. Takuwa;Kazuaki Sampei;Takuya Urushihata;Manami Takahashi;Masafumi Shimojo;S. Uchida;Nobuhiro Nitta;S. Shibata;K. Nagashima;Yoshihiro Ochi;M. Ono;J. Maeda;Y. Tomita;N. Sahara;J. Near;I. Aoki;Kazuhisa Shibata;M. Higuchi
中科院分区:
医学1区
文献类型:
--
作者:
Y. Takado;H. Takuwa;Kazuaki Sampei;Takuya Urushihata;Manami Takahashi;Masafumi Shimojo;S. Uchida;Nobuhiro Nitta;S. Shibata;K. Nagashima;Yoshihiro Ochi;M. Ono;J. Maeda;Y. Tomita;N. Sahara;J. Near;I. Aoki;Kazuhisa Shibata;M. Higuchi

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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测量沿着双光子介观成像的钙信号在兴奋性和抑制性神经元的活的,未麻醉的小鼠。为了监测大脑区域的刺激驱动的激活,在连续两个15分钟的长时间感觉刺激期间测量MRS信号和介观神经活动。在第一阶段,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。在下半年,而兴奋性神经元的活动仍然升高,抑制性神经元的活动显着增强。我们通过测量MRS信号来评估区域神经化学状态,MRS信号与静息状态下Dravet综合征小鼠模型的神经活动和神经化学状态总体一致。介观评估表明,相对于野生型小鼠,皮层中抑制性神经元的活动减少,而兴奋性神经元的活动则减少。与这些观察结果一致,Dravet模型表现出比野生型对照更低的GABA浓度。总的来说,目前的研究表明,MRS测量的Glu和GABA可以反映在清醒状态下产生和释放这些神经递质的神经元的自发和刺激活动。
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.