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3D optogenetic control of arteriole diameter in vivo.

ABSTRACT: Modulation of brain arteriole diameter is critical for maintaining cerebral blood pressure and controlling regional hyperemia during neural activity. However, studies of hemodynamic function in health and disease have lacked a method to control arteriole diameter independently with high spatiotemporal resolution. Here, we describe an all-optical approach to manipulate and monitor brain arteriole contractility in mice in three dimensions using combined in vivo two-photon optogenetics and imaging. The expression of the red-shifted excitatory opsin, ReaChR, in vascular smooth muscle cells enabled rapid and repeated vasoconstriction controlled by brief light pulses. Two-photon activation of ReaChR using a spatial light modulator produced highly localized constrictions when targeted to individual arterioles within the neocortex. We demonstrate the utility of this method for examining arteriole contractile dynamics and creating transient focal blood flow reductions. Additionally, we show that optogenetic constriction can be used to reshape vasodilatory responses to sensory stimulation, providing a valuable tool to dissociate blood flow changes from neural activity.

SUBMITTER: O'Herron PJ

PROVIDER: S-EPMC9481242 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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3D optogenetic control of arteriole diameter in vivo.

O'Herron Philip J PJ Hartmann David A DA Xie Kun K Kara Prakash P Shih Andy Y AY

eLife 20220915

Modulation of brain arteriole diameter is critical for maintaining cerebral blood pressure and controlling regional hyperemia during neural activity. However, studies of hemodynamic function in health and disease have lacked a method to control arteriole diameter independently with high spatiotemporal resolution. Here, we describe an all-optical approach to manipulate and monitor brain arteriole contractility in mice in three dimensions using combined in vivo two-photon optogenetics and imaging. ...[more]

PMID: 36107146

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Project description:Electrical and pharmacological stimulation methods are commonly used to study neuronal brain circuits in vivo, but are problematic, because electrical stimulation has limited specificity, while pharmacological activation has low temporal resolution. A recently developed alternative to these methods is the use of optogenetic techniques, based on the expression of light sensitive channel proteins in neurons. While optogenetics have been applied in in vitro preparations and in in vivo studies in rodents, their use to study brain function in nonhuman primates has been limited to the cerebral cortex. Here, we characterize the effects of channelrhodopsin-2 (ChR2) transfection in subcortical areas, i.e., the putamen, the external globus pallidus (GPe) and the ventrolateral thalamus (VL) of rhesus monkeys. Lentiviral vectors containing the ChR2 sequence under control of the elongation factor 1? promoter (pLenti-EF1? -hChR2(H134R)-eYFP-WPRE, titer 10? particles/ml) were deposited in GPe, putamen and VL. Four weeks later, a probe combining a conventional electrode and an optic fiber was introduced in the previously injected brain areas. We found light-evoked responses in 31.5% and 32.7% of all recorded neurons in the striatum and thalamus, respectively, but only in 2.5% of recorded GPe neurons. As expected, most responses were time-locked increases in firing, but decreases or mixed responses were also seen, presumably via ChR2-mediated activation of local inhibitory connections. Light and electron microscopic analyses revealed robust expression of ChR2 on the plasma membrane of cell somas, dendrites, spines and terminals in the striatum and VL. This study demonstrates that optogenetic experiments targeting the striatum and basal ganglia-related thalamic nuclei can be successfully achieved in monkeys. Our results indicate important differences of the type and magnitude of responses in each structure. Experimental conditions such as the vector used, the number and rate of injections, or the light stimulation conditions have to be optimized for each structure studied.

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3D optogenetic control of arteriole diameter in vivo.

Publications

3D optogenetic control of arteriole diameter in vivo.

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