title: Dopamine D1/D5 receptor signaling regulates synaptic cooperation and competition in hippocampal CA1 pyramidal neurons via sustained ERK1/2 activation.
abstract: Synaptic cooperation and competition are important components of synaptic plasticity that tune synapses for the formation of associative long-term plasticity, a cellular correlate of associative long-term memory. We have recently reported that coincidental activation of weak synapses within the vicinity of potentiated synapses will alter the cooperative state of synapses to a competitive state thus leading to the slow decay of long-term plasticity, but the molecular mechanism underlying this is still unknown. Here, using acute hippocampal slices of rats, we have examined how increasing extracellular dopamine concentrations interact and/or affect electrically induced long-term potentiation (LTP) in the neighboring synapses. We demonstrate that D1/D5-receptor-mediated potentiation at the CA1 Schaffer collateral synapses differentially regulates synaptic co-operation and competition. Further investigating the molecular players involved, we reveal an important role for extracellular signal-regulated kinases-1 and 2 (ERK1/2) as signal integrators and dose-sensors. Interestingly, a sustained activation of ERK1/2 pathway seems to be involved in the differential regulation of synaptic associativity. The concentration-dependent effects of the modulatory transmitter, as demonstrated for dopaminergic signaling in the present study, might offer additional computational power by fine tuning synaptic associativity processes for establishing long-term associative memory in neural networks.
authors.affiliation: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.|Neurobiology/Aging Program, Life Sciences Institute (LSI), National University of Singapore, Singapore.
authors.forename: Mahesh
authors.initials: M
authors.lastname: Shivarama Shetty
authors.affiliation: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Suma
authors.initials: S
authors.lastname: Gopinadhan
authors.affiliation: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.|Neurobiology/Aging Program, Life Sciences Institute (LSI), National University of Singapore, Singapore.
authors.forename: Sreedharan
authors.initials: S
authors.lastname: Sajikumar
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009924:Organ Culture Techniques; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000502:physiology*; D050641:Receptors, Dopamine D5 / Q000819:agonists / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*
chemical_list: D018491:Dopamine Agonists; D017447:Receptors, Dopamine D1; D050641:Receptors, Dopamine D5
keywords: D1/D5 receptor; ERK1/2; long-term potentiation; synaptic capture; synaptic tagging