View source for Neurovascular coupling

==Physiological consequences of neural activation==
Brain activation is accompanied by a complex sequence of cellular, metabolic, and vascular processes.  Although the mechanisms linking these events are still under investigation, the basic sequence can be summarized as follows ( <figref>PasleyNV1.jpg</figref>).  Various cellular processes of neurons, such as the restoration of ionic gradients and neurotransmitter recycling, require energy in the form of adenosine triphosphate (ATP).  ATP is synthesized first by glycolysis, which is anaerobic and produces a small amount of ATP, and then by oxidative glucose metabolism, which requires oxygen and produces a large amount of ATP.  In the brain, about 90% of glucose is metabolized by the latter mechanism, i.e., aerobically.  Cerebral metabolism thus depends on a constant supply of both glucose and oxygen.  A continuous supply of these two energy substrates is maintained by CBF, which delivers glucose and oxygen to neural tissue through the complex web of blood vessels in the brain’s vascular system ( <figref>PasleyCVS.jpg</figref>).  Accordingly, during neural activity, increases in oxygen and glucose consumption are followed by an increase in CBF.  Whereas the fractional increases in CBF and glucose consumption are similar in magnitude, oxygen consumption increases much ''less'' than CBF, leading to a net increase in the amount of oxygen present in the blood and tissue.  This oversupply of oxygen due to the mismatch between CBF and oxygen consumption is the basis of blood-oxygenation level dependent (BOLD) fMRI, which detects alterations in levels of deoxygenated hemoglobin and cerebral blood volume.
[[Image:pasleyCVS.jpg|thumb|400px|right|F2|
The cerebral vascular system. A plastic emulsion was injected into the brain vessels, and brain parenchymal tissue was dissolved (Zlokovic & Apuzzo, 1998; provided by permission from Lippincott Williams & Wilkins)]]

While it is clear that alterations in neural activity and metabolism are correlated with changes in CBF, the mechanisms linking these processes are a matter of debate.  One possibility is that blood flow is controlled directly by energy demand. In fact, this idea was originally proposed over a century ago by Roy and Sherrington (1890): “…''the brain possesses an intrinsic mechanism by which its vascular supply can be varied locally in correspondence with local variations of functional activity.''” In this view, regional blood flow is controlled by feedback mechanisms that are sensitive to variations in the concentrations of ionic and molecular metabolic by-products. These by-products, such as K+, nitric oxide (NO), adenosine, carbon dioxide (CO<sub>2</sub>) and arachidonic acid metabolites, may directly or indirectly alter blood flow by depolarizing (or hyperpolarizing) the vascular smooth muscle cells which trigger vasodilation (or vasoconstriction). Although intuitive, the idea that energy supply (i.e., local blood flow) is controlled directly by energy demand (i.e., metabolic activity) appears to be oversimplified. An alternative possibility is that local blood flow is controlled directly by a feedforward mechanism involving neuronal signaling via neurotransmitters (Attwell and Iadecola, 2002; Lauritzen, 2005). Evidence for this mechanism suggests that astrocytes may play an important role in linking neurotransmitter activity to vascular responses (Harder et al., 1998; Pellerin and Magistretti, 2004). Astrocytes are a critical component for glutamate recycling. A cascade of chemical events within the astrocyte may then link the rate of glutamate cycling to the production of vasoactive chemical agents (Raichle and Mintun, 2006). In this view, neurovascular coupling is mediated by neuronal signaling mechanisms via glial pathways, rather than by mechanisms that sense energy consumption.  In addition, neurovascular coupling might be mediated by diffusion of products of neuronal activity ''without'' the involvement of glial cells (Attwell and Iadecola, 2002).  Finally, there is evidence that direct neuronal innervation of smooth muscle cells can also control blood flow (Hamel, 2004; Iadecola, 2004).  Ultimately, it is likely that multiple mechanisms, both feedforward and feedback, function to mediate neurovascular coupling (Attwell and Iadecola, 2002; Lauritzen, 2005; Uludag et al., 2004). It is important to note that neurovascular coupling must provide for continuous brain function which requires metabolic nutrients and the elimination of waste products such as CO<sub>2</sub> and excessive heat.  The fact that this process occurs on a fine spatio-temporal scale provides the basis for many powerful neuroimaging techniques.