The Journal of Neuroscience, February 1, 2000, 20(3):969-976
Metabotropic Glutamate Receptors Trigger Homosynaptic Protein
Synthesis to Prolong Long-Term Potentiation
Clarke R.
Raymond1, 3,
Vida L.
Thompson2, 3,
Warren
P.
Tate2, 3, and
Wickliffe C.
Abraham1, 3
Departments of 1 Psychology and
2 Biochemistry and the 3 Neuroscience Research
Centre, University of Otago, Dunedin, New Zealand
We investigated the mechanisms by which previous "priming"
activation of group I metabotropic glutamate receptors (mGluRs) facilitates the persistence of long-term potentiation (LTP) in area CA1
of rat hippocampal slices. Priming of LTP was elicited by either
pharmacological or synaptic activation of mGluRs before a weak tetanic
stimulus that normally produced only a rapidly decaying phase of LTP
that did not involve protein synthesis or mGluRs. Pharmacological
priming of LTP persistence by a selective group I mGluR agonist was
blocked by an inhibitor of group I mGluRs and by inhibitors of
translation, but not by a transcriptional inhibitor. The same mGluR
agonist increased 35S-methionine incorporation into slice
proteins. LTP could also be facilitated using a synaptic stimulation
priming protocol, and this effect was similarly blocked by group I
mGluR and protein synthesis inhibitors. Furthermore, using a
two-pathway protocol, the synaptic priming of LTP was found to be
input-specific. To test for the contribution of group I mGluRs and
protein synthesis to LTP in nonprimed slices, a longer duration control
tetanization protocol was used to elicit a more slowly decaying form of
LTP than did the weak tetanus used in the previous experiments. The persistence of the LTP induced by this stronger tetanus was dependent on mGluR activation and protein synthesis but not on transcription. Together, these results suggest that mGluRs couple to nearby protein synthesis machinery to homosynaptically regulate an intermediate phase
of LTP dependent on new proteins made from pre-existing mRNA.
Key words:
LTP; mGluRs; metaplasticity; protein synthesis; synaptic
plasticity; hippocampus
Copyright © 2000 Society for Neuroscience 0270-6474/00/203969-08$05.00/0