title: NMDA and dopamine converge on the NMDA-receptor to induce ERK activation and synaptic depression in mature hippocampus.
abstract: The formation of enduring internal representation of sensory information demands, in many cases, convergence in time and space of two different stimuli. The first conveys the sensory input, mediated via fast neurotransmission. The second conveys the meaning of the input, hypothesized to be mediated via slow neurotransmission. We tested the biochemical conditions and feasibility for fast (NMDA) and slow (dopamine) neurotransmission to converge on the Mitogen Activated Protein Kinase signaling pathways, crucial in several forms of synaptic plasticity, and recorded its effects upon synaptic transmission. We detected differing kinetics of ERK2 activation and synaptic strength changes in the CA1 for low and high doses of neurotransmitters in hippocampal slices. Moreover, when weak fast and slow inputs are given together, they converge on ERK2, but not on p38 or JNK, and induce strong short-term synaptic depression. Surprisingly, pharmacological analysis revealed that a probable site of such convergence is the NMDA receptor itself, suggesting it serves as a detector and integrator of fast and slow neurotransmission in the mature mammalian brain, as revealed by ERK2 activation and synaptic function.
authors.affiliation: Center for Brain and Behavior, Department of Neurobiology and Ethology, Haifa University, Haifa, Israel.
authors.forename: Hanoch
authors.initials: H
authors.lastname: Kaphzan
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: O'Riordan
authors.forename: Kile P
authors.initials: KP
authors.lastname: Mangan
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Levenson
authors.forename: Kobi
authors.initials: K
authors.lastname: Rosenblum
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000008:administration & dosage / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D008959:Models, Neurological; D016202:N-Methylaspartate / Q000008:administration & dosage / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
chemical_list: D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D019950:Mitogen-Activated Protein Kinase 1; D004298:Dopamine