Activation -flow coupling in the rat somatosensory cortex

A fundamental aspect of brain physiology is the coupling between neuronal activation and changes in cerebral blood flow (CBF), herein referred to as activation-flow coupling (AFC). Since the phenomenon of AFC was originally proposed in 1890, the exact mediators and mechanisms involved remain unknown. This thesis studies the physiology of AFC in a rat model using forepaw stimulation. Our results suggest a complex sequence of events during stimulation. The onset of functional stimulation leads to an increase in neuronal activity and a resulting rise in tissue metabolism. Vasoactive diffusible agents are in turn released and cause ‘local’ vascular changes near the site of increased neuronal activity. These ‘local’ vascular changes can be assessed by the magnitude of the CBF response. In addition to ‘local’ vascular changes a significant transformation occurs in larger upstream arterioles whose branches supply the activated area. The mechanism for this ‘remote’ vasodilatation remains unknown, but a functional measure of the changes in the more proximal vasculature can be obtained from the temporal dynamics of the CBF response. Results from this thesis also demonstrate complex coupling exists between CBF and tissue metabolism during functional activation. Immediately after the onset of stimulation an initial peak in CBF occurs regardless of stimulus length. These CBF changes are accompanied by an overshoot in tissue pO 2; suggesting a mismatch between CBF changes and tissue metabolism for the first few seconds of stimulation. During protracted stimulation CBF and tissue metabolism are tightly coupled with CBF maintained at a reduced plateau level while tissue pO2 only slightly above baseline. Depending on the stimulus duration an uncoupling between CBF and tissue metabolism can occur during the post-stimulus period. For longer stimulus lengths CBF quickly returns to baseline while a prominent undershoot is present in tissue pO 2. This undershoot presumably reflects an increase in tissue metabolism that may be required to compensate for the metabolic debt incurred with protracted stimulation. It is hoped from this animal model that a greater understanding of AFC will provide further insight into the basis of functional neuroimaging techniques that use regional CBF changes as surrogate marker for neuronal activity