Oxidative and nonoxidative metabolism of excited neurons and astrocytes.
There is evidence that the metabolic responses to afferent and efferent nervous activity are dissociated at sites of neuronal excitation in brain. Whether efferent activity follows afferent activity depends on the responsiveness of postsynaptic neurons, which in turn depends on the summation of excitatory and inhibitory postsynaptic potentials. The afferent activity excites the presynaptic terminals and astrocytes, whereas the efferent activity arises from excitation of the dendrites of projection neurons. Measurements in vivo indicate that primary stimulation, elicited by simple stimuli, gives rise to limited increases of energy metabolism associated with afferent activity. Reports show that a major consequence of afferent activity, in addition to the release of excitatory neurotransmitters from presynaptic terminals and the import of glutamate by astrocytes, is the establishment of rates of blood flow commensurate with increased rates of oxidative energy metabolism associated with efferent activity projecting from the site of activation. Increased flow rates overcome the inherent diffusion limitation of oxygen delivery, while increased rates of glycolysis elevate tissue pyruvate contents, to which oxygen consumption rates are matched. In vivo, neurons in the baseline condition sustain no net import of pyruvate or lactate, and the reported changes of metabolism subserving afferent and efferent activity are additive rather than linked by significant additional transfer of pyruvate or lactate from astrocytes. The dissociation of blood flow changes from efferent activity weakens the identification of functional states by changes of blood flow alone. It raises the possibility that uncoupling of flow from oxidative metabolism occurs at sites of low efferent activity, such that dissociations of flow and glycolysis from oxygen consumption signify imbalances of afferent and efferent activity.
Gjedde
Albert
A
Pathophysiology and Experimental Tomography Center, Aarhus University Hospital, Aarhus University, Denmark 8000.
Marrett
Sean
S
Vafaee
Manouchehr
M
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001921:Brain / Q000098:blood supply / Q000378:metabolism*; D002560:Cerebrovascular Circulation; D004734:Energy Metabolism; D005947:Glucose / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006019:Glycolysis / Q000502:physiology; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D019289:Pyruvic Acid / Q000378:metabolism; D051381:Rats; D009435:Synaptic Transmission / Q000502:physiology*
D019344:Lactic Acid; D018698:Glutamic Acid; D019289:Pyruvic Acid; D000255:Adenosine Triphosphate; D005947:Glucose