Stimulation of phosphoinositide turnover by excitatory amino acids. Pharmacology, development, and role in visual cortical plasticity.
Theoretical analysis suggests that in the visual cortex during early postnatal development, afferent activity can yield either an increase or a decrease in synaptic strength depending on the pattern of EAA receptor activation in cortical neurons. This motivated us to study the mechanism of EAA-stimulated phosphoinositide turnover in visual cortex. Available evidence suggests that PI hydrolysis is stimulated by EAAs primarily at a single receptor site (Q2 receptor), and that this site is distinct from both the traditional quisqualate (Q1) receptor and the NMDA receptor. NMDA does, however, inhibit EAA-stimulated PI turnover in visual cortex, confirming that the Q2 receptor is on visual cortical neurons (as opposed to glia). We find that Q2 receptors in the neocortex are expressed transiently during postnatal development. The developmental time-course of EAA-stimulated PI turnover correlates precisely with the critical period when synaptic modifications are most readily elicited in visual cortex by changes in sensory experience. The compound AP3 can inhibit EAA-stimulated PI turnover, probably by acting as a partial Q2 agonist, and under some circumstances AP3 evidently can interfere with experience-dependent synaptic modifications. Increases in synaptic strength in visual cortex, as elsewhere, have been linked specifically to activation of NMDA receptors. We propose that decreases in synaptic strength may be specifically related to activation of the Q2 receptor. Further tests of this hypothesis will require the development of selective and potent antagonists.
Bear
M F
MF
Center for Neural Science, Brown University, Providence, Rhode Island 02912.
Dudek
S M
SM
D000596:Amino Acids / Q000502:physiology*; D000818:Animals; D007839:Functional Laterality / Q000502:physiology; D009473:Neuronal Plasticity; D009799:Ocular Physiological Phenomena; D010716:Phosphatidylinositols / Q000378:metabolism*; D018091:Receptors, AMPA; D017981:Receptors, Neurotransmitter / Q000378:metabolism / Q000502:physiology; D014793:Visual Cortex / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*
D000596:Amino Acids; D010716:Phosphatidylinositols; D018091:Receptors, AMPA; D017981:Receptors, Neurotransmitter