Roles of Protein Kinase A and Protein Kinase G in Synaptic Plasticity in the Visual Cortex

Abstract

Monocular deprivation leads to clear physiological and anatomical changes in the visual cortex known as ocular dominance plasticity. Protein kinase A (PKA) is necessary for ocular dominance plasticity, while protein kinase G (PKG) is not. We have now tested the role of PKA and PKG in long-term potentiation (LTP) and long-term depression (LTD). We have shown that PKA inhibitors have a major effect on both LTP and LTD in the visual cortical slices, whereas a PKG inhibitor affects LTP but not LTD. The PKA activator, 8-chloroadenosine-3',5'-monophosphorothioate, Sp-isomer (Sp-8-Cl-cAMPS), by itself induces a slowly rising form of LTP, which is occluded by theta-burst stimulation (TBS)-induced LTP. These results support the point that the PKA signaling pathway is crucial for neuronal plasticity in visual cortex, and the dissociation of the role of PKA and PKG in long-term synaptic plasticity in the visual cortex suggests that LTP alone is not sufficient to support ocular dominance plasticity, or LTD plays a more fundamental role than LTP in ocular dominance plasticity.

Bidirectional Trafficking of Prostaglandin E2Receptors Involved in Long-Term Potentiation in Visual Cortex

“…In layer II/III of the visual cortex, however, genetic and pharmacological analyses demonstrated that the inhibition of PKA activity blocks the induction of TBS-induced and pairing-induced LTP, both of which are associated with E-LTP (Hensch et al, 1998;Liu et al, 2003), which is consistent with the current results demonstrating the absence of E-LTP with EP2-knockdown manipulation. The discrepancy in the PKA-involved phase of LTP between the hippocampal CA1 area and visual cortex may be explained by the regional specificity, as mentioned above.…”

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

“…Unfortunately, no such mutants are available; however, retinotopy, receptive field area, response quality, basal synaptic transmission, and LTP were all normal in RII␤Ϫ/Ϫ mice. Furthermore, acute application of PKA inhibitors directly to visual cortex also blocks ODP and LTD (Beaver et al, 2001;Liu et al, 2003). These data strongly suggest that neither wiring errors nor compensation is the cause of impaired plasticity in RII␤Ϫ/Ϫ mice.…”

“…Because PKA is crucial for LTP, LTD, and ODP (Beaver et al, 2001;Liu et al, 2003) but targeted deletion of the RI␤ subunit blocks some forms of LTP and LTD without compromising ODP (Hensch et al, 1998a), we investigated whether these forms of LTP and LTD share a common requirement with ODP for the activation of the RII␤ isoform of PKA (see above results).…”

“…ODP produced by monocular deprivation (MD) during a critical period of development is blocked by inhibition of NMDARs or PKA (Bear et al, 1990;Daw et al, 1999;Beaver et al, 2001). Similarly, NMDA-and PKA-dependent LTP and LTD have been demonstrated, often using the same stimulation protocols, in both visual cortex and hippocampus (Frey et al, 1993;Kirkwood et al, 1993;Huang et al, 1994;Brandon et al, 1997;Nguyen and Kandel, 1997;Hensch et al, 1998a;Otmakhova et al, 2000;Liu et al, 2003). Finally, Ca 2ϩ influx through NMDARs is essential for the induction of LTP or LTD in both regions (Tsumoto, 1992;Malenka, 1994).…”

“…Hensch et al (1998a) showed that knock-out of the RI␤ subunit of PKA [despite compensation by RI␣ subunits (Amieux et al, 1997)] blocks LTP and LTD, but not ODP. In contrast, Rp-8-ClcAMPS (8-chloroadenosine-3Ј,5Ј-cyclic monophosphorothioate, Rp-isomer), which inhibits both RI-and RII-PKA, blocks not only LTP and LTD, but also abolishes ODP (Beaver et al, 2001;Liu et al, 2003). One reason for this difference may be that only RII subunits are localized to glutamate receptor complexes by A-kinase anchoring proteins (AKAPs) (Colledge and Scott, 1999), which enable PKA to regulate glutamate receptor-mediated synaptic activity (Rosenmund et al, 1994;Westphal et al, 1999;Tavalin et al, 2002).…”