Neurons of a limited subthalamic area mediate elevations in cortical cerebral blood flow evoked by hypoxia and excitation of neurons of the rostral ventrolateral medulla

Sympathoexcitatory reticulospinal neurons of the rostral ventrolateral medu lla (RVLM) are oxygen detectors excited by hypoxia to globally elevate regi onal cerebral blood flow (rCBF). The projection, which accounts for >50% of hypoxic cerebral vasodilation, relays through the medullary vasodilator ar ea (MCVA). However, there are no direct cortical projections from the RVLM/ MCVA, suggesting a relay that diffusely innervates cortex and possibly ori ginates in thalamic nuclei. Systematic mapping by electrical microstimulati on of the thalamus and subthalamus revealed that elevations in rCBF were el icited only from a limited area, which encompassed medial pole of zona ince rta, Forel's field, and prerubral zone. Stimulation (10 sec train) at an ac tive site increased rCBF by 25 +/- 6%. Excitation of local neurons with kai nic acid mimicked effects of electrical stimulation by increasing rCBF. Sti mulation of the subthalamic cerebrovasodilator area (SVA) with single pulse s (0.5 msec; 80 muA) triggered cortical EEG burst-CBF wave complexes with l atency 24 +/- 5 msec, which were similar in shape to complexes evoked from the MCVA. Selective bilateral lesioning of the SVA neurons (ibotenic acid, 2 mug, 200 nl) blocked the vasodilation elicited from the MCVA and attenuat ed hypoxic cerebrovasodilation by 52 +/- 12% ( p < 0.05), whereas hypercarb ic vasodilation remained preserved. Lesioning of the vasodilator site in th e basal forebrain failed to modify SVA-evoked rCBF increase. We conclude th at (1) excitation of intrinsic neurons of functionally restricted region of subthalamus elevates rCBF, (2) these neurons relay signals from the MCVA, which elevate rCBF in response to hypoxia, and (3) the SVA is a functionall y important site conveying vasodilator signal from the medulla to the telen cephalon.