Tetanic stimulation and metabotropic glutamate receptor agonists modify synaptic responses and protein kinase activity in rat auditory cortex

We investigated whether tetanic-stimulation and activation of metabotropic glutamate receptors (mGluRs) can modify field-synaptic-potentials and prote in kinase activity in rat auditory cortex, specifically protein kinase A (P KA) and protein kinase C (PKC). Tetanic stimulation (50 Hz, 1 s) increases PKA and PKC activity only if the CNQX-sensitive field-EPSP (f-EPSP) is also potentiated. If the f-EPSP is unchanged, then PKA and PKC activity remains unchanged. Tetanic stimulation decreases a bicuculline-sensitive field-IPS P (f-TPSP), and this occurs whether the f-EPSP is potentiated or not. Poten tiation of the f-EPSP is blocked by antagonists of mGluRs (MCPG) and PKC (c alphostin-C, tamoxifen), suggesting that the potentiation of the f-EPSP is dependent on mGluRs and PKC. PKC antagonists block the rise in PKC and PKA activity, which suggests that these may be coupled. In contrast, ACPD (agon ist at mGluRs) decreases both the f-EPSP and the f-IPSP, but increases PKC and PKA activity. Quisqualate (group I mGluR agonist), decreases the f-IPSP , and increases PKA activity, suggesting that the increase in PKA activity is a result of activation of group I mGluRs. Additionally, the increase in PKC and PKA activity appears to be independent of the decrease of the f-EPS P and f-IPSP, because PKC antagonists block the increase in PKC and PKA act ivity levels but do not block ACPD's effect on the f-EPSP or f-IPSP. These data suggest that group I mGluRs are involved in potentiating the f-EPSP by a PKC and possibly PKA dependent mechanism which is separate from the mech anism that decreases the f-EPSP and f-IPSP. (C) 2001 Elsevier Science B.V. All rights reserved.