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Learning‐specific, time‐dependent increases in hippocampal Ca 2+ /calmodulin‐dependent protein kinase II activity and AMPA GluR1 subunit immunoreactivity
Author(s) -
Cammarota Martín,
Bernabeu Ramón,
Levi de Stein Miguelina,
Izquierdo Iván,
Medina Jorge H.
Publication year - 1998
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.1998.00254.x
Subject(s) - ampa receptor , long term potentiation , hippocampal formation , glutamate receptor , hippocampus , camk , protein subunit , phosphorylation , chemistry , nmda receptor , calmodulin , protein kinase a , inhibitory postsynaptic potential , neuroscience , receptor , endocrinology , medicine , biochemistry , biology , enzyme , gene , autophosphorylation
Ca 2+ /calmodulin‐dependent protein kinase II (CAMK II) and one of its target, α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid (AMPA), glutamate receptors have been shown to participate in both long‐term potentiation (LTP) in the hippocampus, and in spatial, as well as in a variety, of learning paradigms. Recently, we were able to demonstrate that the intrahippocampal infusion of a specific inhibitor of CAMK II (KN62) provoked full retrograde amnesia of an inhibitory avoidance learning in rats when given immediately, but not 120 or 240 min, after training. Furthermore, this task is accompanied by a rapid, selective and reversible increase in hippocampal [ 3 H] AMPA receptor binding. Here we report the effect of this aversively motivated learning task on CAMK II activity, and AMPA GluR1 subunit phosphorylation and immunoreactivity in the hippocampus. One trial inhibitory avoidance training is associated with a learning‐specific, time‐dependent increase (25–78%) in both total and Ca 2+ ‐independent activities of CAMK II in the hippocampus of rats killed immediately (0 min), but not 120 min, after training. In addition, immunoblotting experiments showed an increment in the amount of the α‐subunit of CAMK II at 0, 30 and 120 min after training. An increase in the in vitro phosphorylation of α‐ and β‐subunits of CAMK II was also observed in hippocampal synaptosomal membranes (SPM) of trained rats killed immediately and 30 min post‐training. In addition, inhibitory avoidance is accompanied by a 20% increase in GluR1 phosphorylation and a 33% increase in GluR1 immunoreactivity 120 min after training. No significant changes were observed in shocked animals. Phosphorylation of hippocampal SPM from naive control animals in conditions suitable for CAMK II activation resulted in a large increase in the density of [ 3 H] AMPA binding (+ 100%). Taken together, these findings confirm and extend previous data suggesting that CAMK II and AMPA glutamate receptors in the hippocampus participate in the early phase of memory formation of an inhibitory avoidance learning.