title: Chemically-induced long-term potentiation in rat motor cortex involves activation of extracellular signal-regulated kinase cascade.
abstract: The involvement of the extracellular signal-regulated kinase 1/2 (ERK1/2) cascade in long-lasting potentiation of synaptic transmission, induced by tetraethylammonium (TEA) or by elevated extracellular calcium concentration, was investigated in layer V horizontal connections within motor cortex in rat brain slices. Brief application of TEA (25 mM) resulted in a long-lasting potentiation of field potentials by 54+/-12%. A transient exposure of slices to elevated extracellular calcium (5 mM) induced long-lasting potentiation of responses reaching 30+/-8%. The induction of both forms of potentiation was prevented by the exposure of slices to inhibitors of the upstream activator of ERK 1/2, MEK (ERK kinase), U0126 (20 microM) and PD 98059 (50 microM). PhosphoERK2 immunoreactivity was transiently increased above baseline levels 15 min after termination of the exposure of slices to either TEA or elevated calcium concentration. Both forms of potentiation were partially occluded by Sp-adenosine 3',5'-cyclic monophosphorothioate triethylammonium salt (Sp-cAMPS; 100 microM), an activator of cAMP-dependent protein kinase (PKA), and they were blocked after preincubation with Rp-adenosine 3',5'-cyclic monophosphorothioate triethylammonium salt (Rp-cAMPS; 100 microM), a specific inhibitor of PKA activation by cAMP. It has previously been shown that TEA-induced potentiation represents a N-methyl-d-aspartate (NMDA) receptor-independent form of persistent synaptic enhancement, and, on the contrary, calcium-induced potentiation depends on NMDA receptors. Thus, the activation of PKA and the ERK1/2 cascade are required for two forms of chemically induced long-lasting increases of synaptic efficacy in slices of rat motor cortex.
authors.affiliation: Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343 Krakow, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Grzegorzewska
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Przybylo
authors.forename: Anna
authors.initials: A
authors.lastname: Litynska
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Hess
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D004586:Electrophoresis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009044:Motor Cortex / Q000187:drug effects / Q000502:physiology*; D009924:Organ Culture Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology; D019789:Tetraethylammonium / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D026902:Potassium Channel Blockers; D016194:Receptors, N-Methyl-D-Aspartate; D019789:Tetraethylammonium; D048049:Extracellular Signal-Regulated MAP Kinases; D002118:Calcium