title: Optogenetic stimulation of GABA neurons can decrease local neuronal activity while increasing cortical blood flow.
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.
authors.affiliation: Department of Psychiatry, Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, British Columbia, Canada.|Brain Research Center, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Eitan
authors.initials: E
authors.lastname: Anenberg
authors.affiliation: Department of Psychiatry, Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, British Columbia, Canada.|Brain Research Center, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Allen W
authors.initials: AW
authors.lastname: Chan
authors.affiliation: Department of Psychiatry, Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, British Columbia, Canada.|Brain Research Center, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Yicheng
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Psychiatry, Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, British Columbia, Canada.|Brain Research Center, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: LeDue
authors.affiliation: Department of Psychiatry, Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, British Columbia, Canada.|Brain Research Center, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Timothy H
authors.initials: TH
authors.lastname: Murphy
mesh_terms: D000818:Animals; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D000075402:Channelrhodopsins; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004569:Electroencephalography; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D059330:GABAergic Neurons / Q000187:drug effects / Q000502:physiology*; D007395:Interneurons / Q000187:drug effects; D007834:Lasers; D008297:Male; D051379:Mice; D062308:Optogenetics / Q000379:methods*; D010775:Photic Stimulation; D011810:Quinoxalines / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D000075402:Channelrhodopsins; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D011810:Quinoxalines; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D005680:gamma-Aminobutyric Acid; D016291:Dizocilpine Maleate