Critical role of the subthalamic vasodilator area (SVA) in functional increase of cortical blood flow(CBF).

Abstract

Activation of somatosensory (Smt) cortical neurons in response to stimulation of whiskers in rat increases local CBF through the unknown mechanism. Recently we have discovered that activation of limited subthalamic area increases cortical CBF; while lesions of SVA neurons attenuate whisker-evoked CBF increase in Smt cortex. We hypothesized that activation of SVA produces global metabolism-independent cerebrovasodilation and participates in coupling of local CBF to functional cortical activation. In anesthetized (1.5 % isoflurane) rats instrumented for autoradiographic measurement of CBF (C14-IAP) and glucose metabolism (C14-2DG, CGU) we explored; (a) whether SVA-evoked increase in CBF is global and independent of CGU; and (b) whether lesion of SVA reverses whisker-evoked CBF increase without affecting functional CGU increase in Smt cortex. Electrical stimulation of SVA (trains of 0.5 msec pulses at 50 Hz, 0.5 Hz, 100 μA, 45 min) increased CBF globally by 82±5% (p<0.01, n=6), and independently of CGU triggering neurogenic cerebrovasodilation. Whisker pad stimulation (45 min, 20 Hz, 0.5 msec, 60 μA) increased CBF by 9±2 % (compared to contralateral side, p<0.05, n=5,) and CGU by 14±3 % (p<0.05, n=5) in Smt cortex. Excitotoxic lesion (ibotenate, 100 nl, 1%) of SVA site-specifically attenuated whisker-evoked increase in CBF in the Smt cortex by 89% (p<0.01, n=6), while CGU increase remained unaffected (15±3%, p<0.01) as determined 5 days after the lesion. We conclude that SVA is an important element of the intrinsic brain cerebrovasodilator circuitry, which when activated produces metabolism independent, i.e. neurogenic, cerebrovasodilation and participates in coupling between functional neuronal activation and local cerebrovasodilation. Supported by NINDS grant RO1 NS36154-08.