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Dendritic Ca 2+ accumulations and metabotropic glutamate receptor activation associated with an n‐methyl‐d‐aspartate receptor‐independent long‐term potentiation in hippocampal CA1 neurons
Author(s) -
Petrozzino Jeffrey J.,
Connor John A.
Publication year - 1994
Publication title -
hippocampus
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.767
H-Index - 155
eISSN - 1098-1063
pISSN - 1050-9631
DOI - 10.1002/hipo.450040504
Subject(s) - long term potentiation , chemistry , nmda receptor , metabotropic glutamate receptor , excitatory postsynaptic potential , neurotransmission , glutamate receptor , biophysics , neuroscience , biochemistry , receptor , biology
Bathing hippocampal slices in the potassium channel blocker tetraethylammonium (TEA), while stimulating the Schafer collaterals at a low frequency, induces Ca 2+ ‐dependent, N ‐methyl‐D‐aspartate (NMDA) receptor‐independent long‐term potentiation of synaptic transmission (LTP k ) in CA1 neurons. We have combined ratio imaging of fura‐2 and mag‐fura‐5 in hippocampal CA1 neurons with intracellular and field recordings to evaluate postsynaptic Ca 2+ changes that occur in the induction of LTP k . Test stimuli were applied at 0.05 Hz to stratum radiatum in the presence of the NMDA receptor antagonists D , L ‐2‐amino‐5‐phosphonovaleric acid (100μM) or MK‐801 (10μM). During TEA exposure (15–25 mM; 10 min), cells fired prolonged action potentials both spontaneously and in response to test stimuli resulting in transient, micromolar Ca 2+ accumulations in both somata and dendrites. The initial EPSP slope, measured 60 min after TEA wash‐out, was potentiated to approximately 200% of control. The Ca 2+ channel blocker nimodipine (10 μM) greatly reduced Ca 2+ transients in both magnitude and duration and prevented LTP k induction. Pretreatment of slices with compounds that block metabotropic glutamate receptor (mGluR)‐stimulated phosphoinositide hydrolysis, L ‐2‐amino‐3‐phosphonopropionic acid ( L ‐AP3, 50‐200 μM) or L ‐aspartate‐β‐hydroxamate (50–100 μM), as well as protein kinase C (PKC) inhibitors (sphingosine, 20 μM; RO‐31‐8220, 0.2 μM; or calphostin C, 2 μM) also blocked LTP k . Ca 2+ transients were unaffected by L ‐AP3 or RO‐31‐8220. These findings suggest that Ca 2+ influx through voltage‐gated channels and co‐activation of PKC by mGluRs are both necessary for induction of LTP k . Activation of mGluRs must also occur in NMDA receptor‐dependent induction paradigms, but is possibly of lesser importance owing to the much greater gating of Ca 2+ directly into the dendritic spines. © 1994 Wiley‐Liss, Inc.