title: Differential involvement of Ca2+/calmodulin-dependent protein kinases and mitogen-activated protein kinases in the dopamine D1/D5 receptor-mediated potentiation in hippocampal CA1 pyramidal neurons.
abstract: Dopaminergic neurotransmission modulates and influences hippocampal CA1 synaptic plasticity, learning and long-term memory mechanisms. Investigating the mechanisms involved in the slow-onset potentiation induced by the dopamine D1/D5 receptor agonists in hippocampal CA1 region, we have reported recently that it could play a role in regulating synaptic cooperation and competition. We have also shown that a sustained activation of MEK/MAP kinase pathway was involved in the maintenance of this long-lasting potentiation (Shivarama Shetty, Gopinadhan, & Sajikumar, 2016). However, the molecular aspects of the induction of dopaminergic slow-onset potentiation are not known. Here, we investigated the involvement of MEK/MAPK pathway and Ca2+-calmodulin-dependent protein kinases (CaMKII and CaMKIV) in the induction and maintenance phases of the D1/D5 receptor-mediated slow-onset potentiation. We report differential involvement of these kinases in a dose-dependent manner wherein at weaker levels of dopaminergic activation, both CaMKII and MEK1/2 activation is necessary for the establishment of potentiation and with sufficiently stronger dopaminergic activation, the role of CaMKII becomes dispensable whereas MEK activation remains crucial for the long-lasting potentiation. The results are interesting in view of the involvement of the hippocampal dopaminergic system in a variety of cognitive abilities including memory formation and also in neurological diseases such as Alzheimer's disease and Parkinson's disease.
authors.affiliation: Department of Physiology, Block MD9, 2 Medical Drive, Yong Loo Lin School of Medicine, National University of Singapore, 117597, Singapore; Neurobiology/Aging Program, 28 Medical Drive, Life Sciences Institute, National University of Singapore, Singapore.
authors.forename: Mahesh Shivarama
authors.initials: MS
authors.lastname: Shetty
authors.affiliation: Department of Physiology, Block MD9, 2 Medical Drive, Yong Loo Lin School of Medicine, National University of Singapore, 117597, Singapore; Neurobiology/Aging Program, 28 Medical Drive, Life Sciences Institute, National University of Singapore, Singapore. Electronic address: phssks@nus.edu.sg.
authors.forename: Sreedharan
authors.initials: S
authors.lastname: Sajikumar
mesh_terms: D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000378:metabolism*; D050641:Receptors, Dopamine D5 / Q000819:agonists / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D018491:Dopamine Agonists; D004791:Enzyme Inhibitors; D017447:Receptors, Dopamine D1; D050641:Receptors, Dopamine D5; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4; C517686:Camk4 protein, rat; D020928:Mitogen-Activated Protein Kinases
keywords: CaMKII; CaMKIV; D1/D5 receptor; LTP; MAPK; MEK