Cerebral blood flow increases evoked by electrical stimulation of rat cerebellar cortex: relation to excitatory synaptic activity and nitric oxide synthesis

Abstract

The purpose of this study was to examine mechanisms involved in the coupling of neuronal activity to cerebral blood flow (CBF). CBF was measured in rat cerebellum using laser-Doppler flowmetry during stimulus-evoked neuronal activity and related to the distribution of the extracellular field potential. Local electrical stimulation of the cerebellar cortex activated a narrow beam of parallel fibers (PFs) 100 microns across and evoked increases of CBF along (On-B) and perpendicular (Off-B) to the beam. Increases of CBF and field potentials were recorded for a distance of up to 1500 microns along the activated beam, and perpendicular to the beam, in a zone approximately 1000 microns wide, i.e. about 10 times wider than the zone in which synaptic excitation took place. CBF increased as a function of stimulus frequency up to 75 Hz, the response being larger On-B than Off-B. TTX abolished both the field potentials and the CBF responses at all frequencies, suggesting that action potentials were mechanistically related to the evoked CBF increases. CBF changes were unchanged by picrotoxin, a blocker of GABA(A) receptors, consistent with the idea that inhibitory synaptic activity does not contribute to CBF increases. The latency to the CBF rise was much shorter On-B than Off-B for the same distance from the stimulating electrode. This may suggest that the CBF response Off-B is dependent on diffusion of vasoactive substances from neuronal structures activated by the parallel fibers On-B. Nitric oxide (NO) synthase inhibition with NG-nitro-L-Arginine increased the time latency to onset of CBF rise by 2-4 times and attenuated the evoked CBF increase by approximately 50%. Sodium nitroprusside, a NO donor, increased baseline CBF, but did not reverse the effects of L-NNA. Thus the initial part of the evoked CBF rise is probably mediated by NO, which also contributes to the later part of the response. This study provides insight into the distribution and mechanism of neurally evoked increases of CBF, of putative importance for the interpretation of activation studies in animals and humans.