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Figure 2 | Behavioral and Brain Functions

Figure 2

From: Response variability in Attention-Deficit/Hyperactivity Disorder: a neuronal and glial energetics hypothesis

Figure 2

A scheme illustrating a glutamatergic neuron (left) a glial cell (astrocyte) and a small blood vessel (right) and the major components contributing to hypotheses 1 and 2 (H1 and H2). Neural activity triggers release of the neurotransmitter glutamate that is taken up into the astrocyte (via GLAST and GLT-1 transporters), and stimulates the breakdown of glycogen, the uptake of glucose, and glycolysis, to produce lactate. Rapid neuronal firing is sustained by the energy provided by the astrocyte-neuron lactate shuttle. Energy demands are high during rapid (burst) and maintained rates of neuronal firing. H1: At times of increased neuronal demand, deficient lactate results in decreased neuronal conversion of lactate to acetyl CoA, decreased ATP formation, deficient ATPase function, delayed restoration of ion gradients, elevated extracellular K+, deficient Na+-dependent transport of glutamate into astrocytes that is required to drive glycolysis and lactate release by the astrocytes. The result is that situationally appropriate firing rates are achieved only episodically. Methylphenidate treatment results in an increase of the extracellular levels of the catecholamines, NA (and DA) that stimulate glycolysis and release of lactate from the astrocytes. This is followed by glycogen replenishment, thereby correcting the energy deficiency, and restoring appropriate firing rates. H2: A deficient supply of lactate for oligodendrocytes in the developing nervous system slows and reduces the synthesis of fatty acids required for the synthesis of myelin. Poorly myelinated axons would transmit action potentials more slowly, accounting for inefficient integration (coherence) between brain regions and for slow reaction times. A number of neurotransmitter receptors present on astrocytes are not illustrated (e.g. muscarinic, α2, DA D3, D4, D5 and receptors for several neuropeptides).

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