Opposed hemodynamic responses following increased excitation and parvalbumin-based inhibition

Lee, Joonhyuk; Stile, Chloe L; Bice, Annie R.; Rosenthal, Zachary P.; Yan, Ping; Snyder, Abraham Z.; J, Lee; Bauer, Adam Q.

doi:10.1177/0271678x20930831

Cited by 43 publications

(47 citation statements)

References 89 publications

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“…2011 ), are assumed to have indirect influence through the inhibition of pyramidal cells, resulting in vasoconstriction ( Urban et al. 2012 ; Lee, Stile, et al. 2021 ), although their exact contribution is complicated by the use of different anesthesia in different studies ( Dahlqvist et al.…”

Section: Discussionmentioning

confidence: 99%

Contribution of Excitatory and Inhibitory Neuronal Activity to BOLD fMRI

Moon

Jiang

et al. 2021

Cerebral Cortex

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The BOLD fMRI response in the cortex is often assumed to reflect changes in excitatory neural activity. However, the contribution of inhibitory neurons to BOLD fMRI is unclear. Here, the role of inhibitory and excitatory activity was examined using multimodal approaches: electrophysiological recording, 15.2 T fMRI, optical intrinsic signal imaging, and modeling. Inhibitory and excitatory neuronal activity in the somatosensory cortex were selectively modulated by 20-s optogenetic stimulation of VGAT-ChR2 and CaMKII-ChR2 mice, respectively. Somatosensory stimulation and optogenetic stimulation of excitatory neurons induced positive BOLD responses in the somatosensory network, whereas stimulation of inhibitory neurons produced biphasic responses at the stimulation site, initial positive and later negative BOLD signals, and negative BOLD responses at downstream sites. When the stimulation duration was reduced to 5 s, the hemodynamic response of VGAT-ChR2 mice to optogenetic stimulation was only positive. Lastly, modeling performed from neuronal and hemodynamic data shows that the hemodynamic response function (HRF) of excitatory neurons is similar across different conditions, whereas the HRF of inhibitory neurons is highly sensitive to stimulation frequency and peaks earlier than that of excitatory neurons. Our study provides insights into the neurovascular coupling of excitatory and inhibitory neurons and the interpretation of BOLD fMRI signals.

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Section: Discussionmentioning

confidence: 99%

Contribution of Excitatory and Inhibitory Neuronal Activity to BOLD fMRI

Moon

Jiang

et al. 2021

Cerebral Cortex

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“…For this reason, optogenetics has been used to selectively stimulate inhibitory neurons ( Urban et al, 2012 ; Zhao et al, 2011 ). With this technique, light-sensitive ion channels, like channelrhodopsin-2 (ChR2), were genetically targeted to specific inhibitory neuron populations and their selective contributions to hemodynamic responses were examined ( Anenberg et al, 2015 ; Dahlqvist et al, 2020 ; Krawchuk et al, 2020 ; Lee et al, 2020a , Lee et al, 2020b ; Uhlirova et al, 2016 ; Vazquez et al, 2018 ). These studies showed that light-evoked GABAergic activity can increase or decrease blood flow and blood volume responses.…”

Section: Introductionmentioning

confidence: 99%

Postsynaptic activity of inhibitory neurons evokes hemodynamic fMRI responses

et al. 2021

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Functional MRI responses are localized to the synaptic sites of evoked inhibitory neurons, but it is unknown whether, or by what mechanisms, these neurons initiate functional hyperemia. Here, the neuronal origins of these hemodynamic responses were investigated by fMRI or local field potential and blood flow measurements during topical application of pharmacological agents when GABAergic granule cells in the rat olfactory bulb were synaptically targeted. First, to examine if postsynaptic activation of these inhibitory neurons was required for neurovascular coupling, we applied an NMDA receptor antagonist during cerebral blood volume-weighted fMRI acquisition and found that responses below the drug application site (up to ~1.5 mm) significantly decreased within ~30 min. Similarly, large decreases in granule cell postsynaptic activities and blood flow responses were observed when AMPA or NMDA receptor antagonists were applied. Second, inhibition of nitric oxide synthase preferentially decreased the initial, fast component of the blood flow response, while inhibitors of astrocyte-specific glutamate transporters and vasoactive intestinal peptide receptors did not decrease blood flow responses. Third, inhibition of GABA release with a presynaptic GABA B receptor agonist caused less reduction of neuronal and blood flow responses compared to the postsynaptic glutamate receptor antagonists. In conclusion, local hyperemia by synaptically-evoked inhibitory neurons was primarily driven by their postsynaptic activities, possibly through NMDA receptor-dependent calcium signaling that was not wholly dependent on nitric oxide.

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“…While we did not specifically test if the photostimulation design affected blood flow in the mice used in this study, it did not affect measures of RSFC in controls. Further, previous reports by our lab have shown that similar photostimulus parameters do not affect hemodynamic measures of brain activity in several transgenic mouse strains expressing ChR2 in different neural populations [91,92]. Finally, the limited scope of our RT-PCR analysis provided associations between expression of select neuroplasticity genes and systems level changes across groups post stroke.…”

Section: Limitations and Future Workmentioning

confidence: 72%

Homotopic contralesional excitation suppresses spontaneous circuit repair and global network reconnections following ischemic stroke

Bice

Xiao

Kong

et al. 2021

Preprint

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Understanding circuit-level changes that affect the brain's capacity for plasticity will inform the design of targeted interventions for treating stroke recovery. We combine optogenetic photostimulation with optical neuroimaging to examine how contralesional excitatory activity affects cortical remodeling after stroke in mice. Following photothrombosis of left primary somatosensory forepaw (S1FP) cortex, mice received chronic excitation of right S1FP, a maneuver mimicking the use of the unaffected limb during recovery. Contralesional excitation suppressed perilesional S1FP remapping and was associated with abnormal patterns of evoked activity in the unaffected limb. Contralesional stimulation prevented the restoration of resting-state functional connectivity (RSFC) within the S1FP network, RSFC in several networks functionally-distinct from somatomotor regions, and resulted in persistent limb-use asymmetry. In stimulated mice, perilesional tissue exhibited suppressed transcriptional changes in several genes important for recovery. These results suggest that contralesional excitation impedes local and global circuit reconnection through suppression of several neuroplasticity-related genes after stroke.

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Opposed hemodynamic responses following increased excitation and parvalbumin-based inhibition

Cited by 43 publications

References 89 publications

Contribution of Excitatory and Inhibitory Neuronal Activity to BOLD fMRI

Contribution of Excitatory and Inhibitory Neuronal Activity to BOLD fMRI

Postsynaptic activity of inhibitory neurons evokes hemodynamic fMRI responses

Homotopic contralesional excitation suppresses spontaneous circuit repair and global network reconnections following ischemic stroke

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