title: Repetition of mGluR-dependent LTD causes slowly developing persistent reduction in synaptic strength accompanied by synapse elimination.
abstract: Synaptic plasticity, the cellular basis of memory, operates in a bidirectional manner. LTP (long-term potentiation) is followed by structural changes that may lead to the formation of new synapses. However, little is known whether LTD (long-term depression) is followed by morphological changes. Here we show that the repetitive induction of metabotropic glutamate receptor (mGluR)-dependent LTD in stable cultures of rat hippocampal slices led to a slowly developing persistent (ranging over weeks) reduction in synaptic strength that was accompanied by the loss of synaptic structures. LTD was induced pharmacologically 1-3 times at 24-h intervals by applying aseptically ACPD (1-aminocyclopentane-1,3-dicarboxylic acid), an agonist of group I/II mGluR, and APV (2-amino-5-phosphonovalerate), an antagonist of the NMDA (N-methyl-D-aspartate) receptor. One ACPD/APV application induced LTD that lasted less than 24 h. After three LTD inductions, however, a gradual attenuation of the fEPSP (field excitatory postsynaptic potential) amplitude and a decrease in the number of pre- and postsynaptic structures were observed. The blockade of LTD by an mGluR antagonist or a protein phosphatase 2B inhibitor abolished the development of the synaptic attenuation. In contrast to our previous finding that the repetitive LTP induction triggered a slowly developing persistent synaptic enhancement, the incremental and decremental forms of synaptic plasticity appeared to occur symmetrically not only on the minutes-hours time order but also on the days-weeks time order.
authors.affiliation: Synaptic Plasticity Group, Graduate School of Frontier Biosciences, Osaka University, Toyonaka, Osaka 560-0043, Japan.
authors.forename: Yo
authors.initials: Y
authors.lastname: Shinoda
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kamikubo
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Egashira
authors.forename: Keiko
authors.initials: K
authors.lastname: Tominaga-Yoshino
authors.forename: Akihiko
authors.initials: A
authors.lastname: Ogura
mesh_terms: D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism* / Q000648:ultrastructure; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D009924:Organ Culture Techniques; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure; D013997:Time Factors
chemical_list: D018094:Receptors, Metabotropic Glutamate