title: Pyramidal neurons are "neurogenic hubs" in the neurovascular coupling response to whisker stimulation.
abstract: The whisker-to-barrel cortex is widely used to study neurovascular coupling, but the cellular basis that underlies the perfusion changes is still largely unknown. Here, we identified neurons recruited by whisker stimulation in the rat somatosensory cortex using double immunohistochemistry for c-Fos and markers of glutamatergic and GABAergic neurons, and investigated in vivo their contribution along with that of astrocytes in the evoked perfusion response. Whisker stimulation elicited cerebral blood flow (CBF) increases concomitantly with c-Fos upregulation in pyramidal cells that coexpressed cyclooxygenase-2 (COX-2) and GABA interneurons that coexpressed vasoactive intestinal polypeptide and/or choline acetyltransferase, but not somatostatin or parvalbumin. The evoked CBF response was decreased by blockade of NMDA (MK-801, -37%), group I metabotropic glutamate (MPEP+LY367385, -40%), and GABA-A (picrotoxin, -31%) receptors, but not by GABA-B, VIP, or muscarinic receptor antagonism. Picrotoxin decreased stimulus-induced somatosensory evoked potentials and CBF responses. Combined blockade of GABA-A and NMDA receptors yielded an additive decreasing effect (-61%) of the evoked CBF compared with each antagonist alone, demonstrating cooperation of both excitatory and inhibitory systems in the hyperemic response. Blockade of prostanoid synthesis by inhibiting COX-2 (indomethacin, NS-398), expressed by ∼40% of pyramidal cells but not by astrocytes, impaired the CBF response (-50%). The hyperemic response was also reduced (-40%) after inhibition of astroglial oxidative metabolism or epoxyeicosatrienoic acids synthesis. These results demonstrate that changes in pyramidal cell activity, sculpted by specific types of inhibitory GABA interneurons, drive the CBF response to whisker stimulation and, further, that metabolically active astrocytes are also required.
authors: Laboratory of Cerebrovascular Research, McGill University, Montréal, Québec H3A 2B4, Canada.
authors: Clotilde
authors: C
authors: Lecrux
authors: Xavier
authors: X
authors: Toussay
authors: Ara
authors: A
authors: Kocharyan
authors: Priscilla
authors: P
authors: Fernandes
authors: Sujay
authors: S
authors: Neupane
authors: Maxime
authors: M
authors: Lévesque
authors: Fabrice
authors: F
authors: Plaisier
authors: Amir
authors: A
authors: Shmuel
authors: Bruno
authors: B
authors: Cauli
authors: Edith
authors: E
authors: Hamel
mesh_terms: D000344:Afferent Pathways / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D018680:Cholinergic Antagonists / Q000494:pharmacology; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004347:Drug Interactions; D004569:Electroencephalography; D004791:Enzyme Inhibitors; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007839:Functional Laterality; D018756:GABA Antagonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D017078:Laser-Doppler Flowmetry / Q000379:methods; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology*; D009943:Organophosphorus Compounds / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D010812:Physical Stimulation / Q000379:methods; D010852:Picrotoxin / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D017966:Pyramidal Cells / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012601:Scopolamine / Q000494:pharmacology; D013003:Somatosensory Cortex / Q000166:cytology*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D014738:Vibrissae / Q000294:innervation*
chemical_list: D018680:Cholinergic Antagonists; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; D009943:Organophosphorus Compounds; D010852:Picrotoxin; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D012601:Scopolamine; C066430:CGP 35348