title: Regional differences in neurovascular coupling in rat brain as determined by fMRI and electrophysiology.
abstract: Increases in neuronal activity induce local increases in cerebral perfusion. However, our understanding of the processes underlying this neurovascular coupling remains incomplete and, particularly, how these vary across the brain. Recent work supports an important role for astrocytes in neurovascular coupling, in large part via activation of their metabotropic glutamate receptors (mGluR). Here, using a combination of functional magnetic resonance imaging (fMRI) and electrophysiology we demonstrate regional heterogeneity in the mechanisms underlying neurovascular coupling. Direct electrical stimulation of the rat hindpaw sensorimotor cortex induces blood oxygenation level dependent (BOLD) and cerebral blood volume (CBV) fMRI responses in several anatomically distinct cortical and subcortical structures. Following intraperitoneal administration of the type 5 mGluR antagonist, MPEP, both BOLD and CBV responses to cortical stimulation were significantly reduced, whilst the local field potential (LFP) responses remained largely constant. Spatially, the degree of reduction in fMRI responses varied between cortical and subcortical regions (primary cortex approximately 18% vs. striatum approximately 66%), and also between primary and secondary cortical areas ( approximately 18% vs. approximately 55%). Similarly, greater decreases in response amplitude were seen in the contralateral secondary cortex ( approximately 91%) and ipsilateral striatum (approximately 70%), compared to the primary cortex (approximately 44%). Following MPEP, a negative component of the BOLD and CBV responses became more apparent, suggesting that different mechanisms mediate vasodilatory and vasoconstrictory responses. Interestingly, under baseline conditions the quantitative relationship between fMRI and LFP responses in cortical and subcortical regions was markedly different. Our data indicate that coupling between neuronal and fMRI responses is neither empirically nor mechanistically consistent across the brain.
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, UK.
authors.forename: H L
authors.initials: HL
authors.lastname: Sloan
authors.forename: V C
authors.initials: VC
authors.lastname: Austin
authors.forename: A M
authors.initials: AM
authors.lastname: Blamire
authors.forename: J W H
authors.initials: JW
authors.lastname: Schnupp
authors.forename: A S
authors.initials: AS
authors.lastname: Lowe
authors.forename: K A
authors.initials: KA
authors.lastname: Allers
authors.forename: P M
authors.initials: PM
authors.lastname: Matthews
authors.forename: N R
authors.initials: NR
authors.lastname: Sibson
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000033:anatomy & histology* / Q000187:drug effects; D002540:Cerebral Cortex / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D004558:Electric Stimulation; D004569:Electroencephalography; D005071:Evoked Potentials / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000502:physiology; D008279:Magnetic Resonance Imaging; D009474:Neurons / Q000378:metabolism; D010100:Oxygen / Q000097:blood; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D064529:Receptor, Metabotropic Glutamate 5; D017470:Receptors, Glutamate / Q000502:physiology; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D017470:Receptors, Glutamate; D018094:Receptors, Metabotropic Glutamate; D018698:Glutamic Acid; C121465:6-methyl-2-(phenylethynyl)pyridine; D010100:Oxygen