Neural and Hemodynamic Responses to Optogenetic and Sensory Stimulation in the Rat Somatosensory Cortex

Abstract

Introducing optogenetics into neurovascular research can provide novel insights into the cell-specific control of the hemodynamic response. To generalize findings from molecular approaches, it is crucial to determine whether light-activated circuits have the same effect on the vasculature as sensory-activated ones. For that purpose, rats expressing channelrhodopsin (ChR2) specific to excitatory glutamatergic neurons were used to measure neural activity, blood flow, hemoglobin-based optical intrinsic signal, and blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) during optogenetic and sensory stimulation. The magnitude of the evoked hemodynamic responses was monotonically correlated with optogenetic stimulus strength. The BOLD hemodynamic response function was consistent for optogenetic and sensory stimuli. The relationship between electrical activities and hemodynamic responses was comparable for optogenetic and sensory stimuli, and better explained by the local field potential (LFP) than the firing rate. The LFP was well correlated with cerebral blood flow, moderately with cerebral blood volume, and less with deoxyhemoglobin (dHb) level. The presynaptic firing rate had little impact on evoking vascular response. Contribution of the postsynaptic LFP to the blood flow response induced by optogenetic stimulus was further confirmed by the application of glutamate receptor antagonists. Overall, neurovascular coupling during optogenetic control of glutamatergic neurons largely conforms to that of a sensory stimulus.

Optogenetic fMRI in the mouse hippocampus: Hemodynamic response to brief glutamatergic stimuli

“…15 Interestingly, the timing of the BOLD response seen in this and our own work is in accordance with a more foundational study of vascular diameter changes in response to sensory stimuli: 32 arteriole diameter increased with a peak at around 2-3 s after stimulation onset, and the response lasted around 5-6 s in total.…”

Neuronal networks and mediators of cortical neurovascular coupling responses in normal and altered brain states

“…While technically possible, such investigations have been more rarely performed [52,67,73,75,76], and the acquisition, synchronization and interpretation of these signals in time and space still remain a challenge.…”

Optogenetic Functional MRI

“…Optogenetic functional magnetic resonance imaging (ofMRI) is a novel technique that combines the spatial resolution of high-field fMRI with the precision of optogenetic stimulation [1][2][3][4][5][6][7][8][9][10][11]38 , enabling cell type-specific mapping of functional neural circuits and their dynamics across the whole brain. Optogenetics allows for specific cell types to be targeted for stimulation by the introduction of light-sensitive trans-membrane conductance channels, called opsins.…”

“…Optogenetics allows for specific cell types to be targeted for stimulation by the introduction of light-sensitive trans-membrane conductance channels, called opsins. Specific elements of neural circuits are genetically modified to express these channels, enabling millisecond-timescale modulation of activity in the intact brain [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] . fMRI provides a non-invasive method of determining the brain's global dynamic response to optogenetic stimulation of specific neural circuits through measurement of the blood-oxygen-level-dependent (BOLD) signal [16][17][18] , which provides an indirect measurement of neuronal activity.…”

“…This enables the detection of neuronal activity in response to targeted stimulation at great distances from the site of stimulation without the need for implantation of invasive recording electrodes [1][2][3][4][5][6][7][8][9][10][11] . ofMRI is advantageous over the more traditional method of performing electrical stimulation during fMRI, which can recruit different cell types near the electrode and thus confound the causal influence of each population 19 .…”