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TitleOptogenetic stimulation of GABA neurons can decrease local neuronal activity while increasing cortical blood flow.
Publication TypeJournal Article
Year of Publication2015
AuthorsAnenberg, Eitan, Allen W. Chan, Yicheng Xie, Jeffrey M. LeDue, and Timothy H. Murphy
JournalJ Cereb Blood Flow Metab
Volume35
Issue10
Pagination1579-86
Date Published2015 Oct
ISSN1559-7016
KeywordsAnimals, Cerebrovascular Circulation, Dizocilpine Maleate, Electroencephalography, Excitatory Amino Acid Antagonists, Female, GABA Antagonists, GABAergic Neurons, gamma-Aminobutyric Acid, Interneurons, Lasers, Male, Mice, Optogenetics, Photic Stimulation, Quinoxalines, Rhodopsin
Abstract

We investigated the link between direct activation of inhibitory neurons, local neuronal activity, and hemodynamics. Direct optogenetic cortical stimulation in the sensorimotor cortex of transgenic mice expressing Channelrhodopsin-2 in GABAergic neurons (VGAT-ChR2) greatly attenuated spontaneous cortical spikes, but was sufficient to increase blood flow as measured with laser speckle contrast imaging. To determine whether the observed optogenetically evoked gamma aminobutyric acid (GABA)-neuron hemodynamic responses were dependent on ionotropic glutamatergic or GABAergic synaptic mechanisms, we paired optogenetic stimulation with application of antagonists to the cortex. Incubation of glutamatergic antagonists directly on the cortex (NBQX and MK-801) blocked cortical sensory evoked responses (as measured with electroencephalography and intrinsic optical signal imaging), but did not significantly attenuate optogenetically evoked hemodynamic responses. Significant light-evoked hemodynamic responses were still present after the addition of picrotoxin (GABA-A receptor antagonist) in the presence of the glutamatergic synaptic blockade. This activation of cortical inhibitory interneurons can mediate large changes in blood flow in a manner that is by and large not dependent on ionotropic glutamatergic or GABAergic synaptic transmission. This supports the hypothesis that activation of inhibitory neurons can increase local cerebral blood flow in a manner that is not entirely dependent on levels of net ongoing neuronal activity.

DOI10.1038/jcbfm.2015.140
Alternate JournalJ. Cereb. Blood Flow Metab.
PubMed ID26082013
PubMed Central IDPMC4640302
Grant ListMOP-12675 / / Canadian Institutes of Health Research / Canada