Long-term potentiation persists in an occult state following mGluR-dependent depotentiation.
Depotentiation, the reversal of long-term potentiation (LTP), can be induced by activation of metabotropic glutamate receptors (mGluRs) or NMDA receptors (NMDARs). Although NMDAR-dependent depotentiation is due to a protein phosphatase-dependent erasure of LTP, the notion that mGluR-dependent depotentiation also involves LTP erasure is controversial. To address this issue we used electrophysiological and biochemical approaches to investigate mGluR-dependent depotentiation in hippocampal slices. Activating group I mGluRs with (R,S)-3,5-dihydroxyphenylglycine (DHPG) induced robust depotentiation in both the CA1 and CA3 regions of hippocampal slices. Western immunoblotting of samples prepared from DHPG-treated slices revealed, however, that activation of group I mGluRs causes a transient increase in phosphorylation of AMPA receptor GluR1 subunits at sites crucial for LTP and under some conditions causes persistent activation of alphaCamKII. The paradoxical ability of DHPG to induce depotentiation while at the same time activating signaling pathways involved in LTP suggests that LTP might not be erased by mGluR-dependent depotentiation. Consistent with this, DHPG-induced depotentiation did not restore the ability of high-frequency stimulation to induce LTP at synapses that had previously undergone saturating levels of LTP. In addition, blocking the expression of DHPG-induced LTD revealed hidden LTP at depotentiated synapses. Our results indicate that LTP and mGluR-dependent LTD can co-exist at excitatory synapses.
Delgado
Jary Y
JY
Interdepartmental PhD Program for Neuroscience, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
O'dell
Thomas J
TJ
D000818:Animals; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000378:metabolism*
D018690:Excitatory Amino Acid Agonists; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1