Regional differences in neurovascular coupling in rat brain as determined by fMRI and electrophysiology

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 ~ 18% vs. striatum ~ 66%), and also between primary and secondary cortical areas (~ 18% vs. ~ 55%). Similarly, greater decreases in response amplitude were seen in the contralateral secondary cortex (~ 91%) and ipsilateral striatum (~ 70%), compared to the primary cortex (~ 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.

Research highlights
► Neurovascular uncoupling by mGluR5 blockade is regionally heterogenous.
► BOLD–LFP relationship varies across different brain regions.
► Different mechanisms mediate vasodilatory and vasoconstrictory responses.