Nonlinear neurovascular coupling in rat sensory cortex by activation of transcallosal fibers

Functional neuroimaging and normal brain function rely on the robust coupling between neural activity and cerebral blood flow (CBF), that is neurovascular coupling. We examined neurovascular coupling in rat sensory cortex in response to direct stimulation of transcallosal pathways, which allows examination of brain regions inaccessible to peripheral stimulation techniques. Using laser-Doppler flowmetry to record CBF and electrophysiologic recordings of local field potentials (LFPs), we show an exponential relation between CBF responses and summed LFP amplitudes. Hemodynamic responses were dependent on glutamate receptor activation. CNQX, an AMPA receptor blocker, strongly attenuated evoked CBF responses and LFP amplitudes at all stimulation frequencies. In comparison, N-methyl D-aspartate (NMDA) receptor blockade by MK801 attenuated CBF responses at high (>7 Hz) but not low (<7 Hz) stimulation frequencies, without affecting evoked LFP amplitudes. This shows the limitation of using LFP amplitudes as indicators of synaptic activity. 7-Nitroindazole, a neuronal nitric oxide synthase inhibitor, and indomethacin, a nonspecific cyclooxygenase inhibitor, attenuated the hemodynamic responses by 50%+/-1% and 48%+/-1%, respectively, without affecting LFP amplitudes. The data suggest that preserved activity of both AMPA and NMDA receptors is necessary for the full CBF response evoked by stimulation of rodent interhemispheric connections. AMPA receptor activation gives rise to a measurable LFP, but NMDA receptor activation does not. The lack of a measurable LFP from neural processes that contribute importantly to CBF may explain some of the difficulties in transforming extracellular current or voltage measurements to a hemodynamic response.