cAMP Levels Increased by Activation of Metabotropic Glutamate Receptors Correlate with Visual Plasticity

Abstract

We have investigated the cAMP level increased by stimulation of metabotropic glutamate receptors (mGluRs) in cat visual cortex during development. The cAMP level increases activated by the general mGluR agonist (1S,3R)-1-amino-1,3-cyclopentane-dicarboxylic acid (ACPD) were closely correlated with the critical period for ocular dominance plasticity in both light- and dark-reared animals. Activation of either group I or group II mGluRs increased the cAMP level. Group II mGluR activation also reduced the forskolin-stimulated cAMP increase. The correlation was emulated by a mixture of groups I, II, and III mGluR agonists but not by agonists applied singly; therefore, the correlation is attributable to activation of multiple groups of mGluRs. The cAMP level increased by the mixture was greater than the sum of the increases produced by the agonists applied singly (super-additive effect), suggesting an interaction between the G-proteins and/or second messengers controlled by these mGluRs. The basal cAMP level also correlated closely with the critical period until shortly after the peak of the critical period. Therefore, the major factor that contributes to the correlation between the ACPD-stimulated cAMP increase and the peak of the critical period is the basal level of cAMP: the activation of multiple mGluRs amplifies the basal cAMP. We suggest that both basal activity of cAMP production and activation of mGluRs may be important in plasticity in the visual cortex.

Opposing effects of protein kinase C and protein kinase A on metabotropic glutamate receptor signaling: Selective desensitization of the inositol trisphosphate/Ca 2+ pathway by phosphorylation of the receptor-G protein-coupling domain

“…Activation of the InsP 3 /Ca 2ϩ pathway by group I mGluRs in neurons has been extensively characterized (1). In addition, stimulation of these receptors has been shown to increase cAMP levels during early developmental stages in the hippocampus (37), during the critical period in the visual cortex (38), and in neuronal cultures (39), although the molecular mechanisms underlying this effect are less well understood.…”

Requirement for the RIIβ Isoform of PKA, But Not Calcium-Stimulated Adenylyl Cyclase, in Visual Cortical Plasticity

“…Second, NMDAR signaling may lead to the inhibition of phosphodiesterases that modulate basal levels of cAMP. Third, G-protein-coupled metabotropic glutamate receptors may stimulate AC via release of ␤␥ subunits, or activation of protein kinase C (Reid et al, 1996). Fourth, crosstalk with the extracellular signal-regulated kinase (ERK) pathway, which is also required for visual cortical plasticity (Di Cristo et al, 2001), may lead to PKA activation.…”

Long-Term Depression Induced by Postsynaptic Group II Metabotropic Glutamate Receptors Linked to Phospholipase C and Intracellular Calcium Rises in Rat Prefrontal Cortex

“…and this value is significantly different from DCG IV-induced LTD depicted in Figure 1 A ( p Ͻ 0.05). Reid et al (1996), Schoepp et al (1996), and Sortino et al (1996) suggested that group II mGluRs can increase cAMP levels. Therefore finally, in additional cells, we tested the effect of selective PKA inhibitor KT5720.…”