A cyclic AMP-dependent form of associative synaptic plasticity induced by coactivation of beta-adrenergic receptors and metabotropic glutamate receptors in rat hippocampus.
Recent studies suggest that increases in intracellular cAMP increase evoked synaptic responses in area CA1 of the hippocampus. We recently reported that activation of metabotropic glutamate receptors (mGluRs) in hippocampal slices potentiates cAMP responses to activation of other receptors that are positively coupled to adenylyl cyclase through Gs. It is possible that by enhancing cAMP responses, mGluRs could markedly potentiate the ability of agonists of Gs-coupled receptors to potentiate synaptic responses in area CA1. Such synergistic activation of a second messenger system could be involved in an associative form of neuronal plasticity in which simultaneous activation of two independent inputs to a cell is required for induction of a given change in synaptic transmission or neuronal excitability. We therefore tested the hypothesis that coactivation of mGluRs and a Gs-coupled receptor (the beta-adrenergic receptor) could lead to large increases in cAMP accumulation in hippocampus and thereby increase synaptic responses in area CA1. We report that coactivation of mGluRs and beta-adrenergic receptors leads to a lasting (> 30 min) increase in the amplitude of evoked population spikes at the Schaffer collateral-CA1 synapse. This effect is not accompanied by an increase in excitatory postsynaptic currents or by a decrease in synaptic inhibition in area CA1, suggesting that it is not mediated by a lasting change in excitatory or inhibitory synaptic transmission. However, coactivation of these receptors leads to a persistent depolarization of CA1 pyramidal cells with a concomitant increase in input resistance.(ABSTRACT TRUNCATED AT 250 WORDS)
Gereau
R W
RW
Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322.
Conn
P J
PJ
D000818:Animals; D000242:Cyclic AMP / Q000502:physiology*; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D004357:Drug Synergism; D004594:Electrophysiology; D005071:Evoked Potentials; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009473:Neuronal Plasticity / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D013569:Synapses / Q000502:physiology*
D011943:Receptors, Adrenergic, beta; D018094:Receptors, Metabotropic Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D000242:Cyclic AMP; D007545:Isoproterenol