Department of Neuroscience, Faculty of Health Sciences, University of Copenhagen, DK-2200, Copenhagen, Denmark.
Laboratory of Pharmaceutical Sciences, Institute of Pharmaceutical Technologies, Faculty of Pharmacy, Medical Academy, Lithuanian University of Health Sciences, LT-50162, Kaunas, Lithuania.
Glia. 2023 Aug;71(8):1830-1846. doi: 10.1002/glia.24370. Epub 2023 Mar 30.
Neurovascular coupling (NVC) modulates cerebral blood flow to match increased metabolic demand during neuronal excitation. Activation of inhibitory interneurons also increase blood flow, but the basis for NVC caused by interneurons is unclear. While astrocyte Ca levels rise with excitatory neural transmission, much less is known with regards to astrocytic sensitivity to inhibitory neurotransmission. We performed two-photon microscopy in awake mice to examine the correlation between astrocytic Ca and NVC, evoked by activation of either all (VGAT ) or only parvalbumin-positive GABAergic interneurons (PV ). Optogenetic stimulation of VGAT and PV in the somatosensory cortex triggered astrocytic Ca increases that were abolished by anesthesia. In awake mice, PV evoked astrocytic Ca responses with a short latency that preceded NVC, whereas VGAT evoked Ca increases that were delayed relative to the NVC response. The early onset of PV evoked astrocytic Ca increases depended on noradrenaline release from locus coeruleus as did the subsequent NVC response. Though the relationship between interneuron activity and astrocytic Ca responses is complex, we suggest that the rapid astrocyte Ca responses to increased PV activity shaped the NVC. Our results underline that interneuron and astrocyte-dependent mechanisms should be studied in awake mice.
神经血管耦合 (NVC) 调节脑血流以匹配神经元兴奋时增加的代谢需求。抑制性中间神经元的激活也会增加血流量,但 NVC 由中间神经元引起的基础尚不清楚。虽然星形胶质细胞 Ca 水平随兴奋性神经传递而升高,但对于星形胶质细胞对抑制性神经递质传递的敏感性知之甚少。我们在清醒小鼠中进行了双光子显微镜检查,以研究由所有(VGAT)或仅表达 Parvalbumin 的 GABA 能中间神经元(PV)的激活引起的星形胶质细胞 Ca 与 NVC 之间的相关性。体感皮层中 VGAT 和 PV 的光遗传学刺激引发了星形胶质细胞 Ca 的增加,而麻醉则消除了这种增加。在清醒的小鼠中,PV 诱发的星形胶质细胞 Ca 反应具有较短的潜伏期,先于 NVC,而 VGAT 诱发的 Ca 增加相对于 NVC 反应延迟。PV 诱发的星形胶质细胞 Ca 增加的早期出现取决于蓝斑核中去甲肾上腺素的释放,随后的 NVC 反应也是如此。尽管中间神经元活动和星形胶质细胞 Ca 反应之间的关系很复杂,但我们认为增加的 PV 活性引起的快速星形胶质细胞 Ca 反应塑造了 NVC。我们的研究结果强调,应该在清醒的小鼠中研究中间神经元和星形胶质细胞依赖的机制。