Neurovascular coupling during optogenetic functional activation: Local and remote stimulus-response characteristics, and uncoupling by spreading depression

Maximilian Böhm, David Y. Chung, Carlos A. Gómez, Tao Qin, Tsubasa Takizawa, Homa Sadeghian, Kazutaka Sugimoto, Sava Sakadžić, Mohammad A. Yaseen, Cenk Ayata

研究成果: Article査読

4 被引用数 (Scopus)

抄録

Neurovascular coupling is a fundamental response that links activity to perfusion. Traditional paradigms of neurovascular coupling utilize somatosensory stimulation to activate the primary sensory cortex through subcortical relays. Therefore, examination of neurovascular coupling in disease models can be confounded if the disease process affects these multisynaptic pathways. Optogenetic stimulation is an alternative to directly activate neurons, bypassing the subcortical relays. We employed minimally invasive optogenetic cortical activation through intact skull in Thy1-channelrhodopsin-2 transgenic mice, examined the blood flow changes using laser speckle imaging, and related these to evoked electrophysiological activity. Our data show that optogenetic activation of barrel cortex triggers intensity- and frequency-dependent hyperemia both locally within the barrel cortex (>50% CBF increase), and remotely within the ipsilateral motor cortex (>30% CBF increase). Intriguingly, activation of the barrel cortex causes a small (∼10%) but reproducible hypoperfusion within the contralateral barrel cortex, electrophysiologically linked to transhemispheric inhibition. Cortical spreading depression, known to cause neurovascular uncoupling, diminishes optogenetic hyperemia by more than 50% for up to an hour despite rapid recovery of evoked electrophysiological activity, recapitulating a unique feature of physiological neurovascular coupling. Altogether, these data establish a minimally invasive paradigm to investigate neurovascular coupling for longitudinal characterization of cerebrovascular pathologies.

本文言語English
ページ(範囲)808-822
ページ数15
ジャーナルJournal of Cerebral Blood Flow and Metabolism
40
4
DOI
出版ステータスPublished - 2020 4 1

ASJC Scopus subject areas

  • 神経学
  • 臨床神経学
  • 循環器および心血管医学

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