Developmental switch in synaptic mechanisms of hippocampal metabotropic glutamate receptor-dependent long-term depression.
The presynaptic and postsynaptic properties of synapses change over the course of postnatal development. Therefore, synaptic plasticity mechanisms would be expected to adapt to these changes to facilitate alterations of synaptic strength throughout ontogeny. Here, we identified developmental changes in long-term depression (LTD) mediated by group 1 metabotropic glutamate receptors (mGluRs) and dendritic protein synthesis in hippocampal CA1 slices (mGluR-LTD). In slices prepared from adolescent rats [postnatal day 21 (P21) to P35], mGluR activation induces LTD and a long-term decrease in AMPA receptor (AMPAR) surface expression, both of which require protein synthesis. In neonatal animals (P8-P15), mGluR-LTD is independent of protein synthesis and is not associated with changes in the surface expression of AMPARs. Instead, mGluR-LTD at neonatal synapses results in large decreases in presynaptic function, measured by changes in paired-pulse facilitation and the rate of blockade by the use-dependent NMDA receptor blocker (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate. Conversely, mGluR-LTD at mature synapses results in little or no change in presynaptic function, suggesting a postsynaptic mechanism of expression. The developmental switch in the synaptic mechanisms of LTD would differentially affect synapse dynamics and perhaps information processing over the course of postnatal development.
Nosyreva
Elena D
ED
Center for Basic Neuroscience, Department of Physiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9111, USA.
Huber
Kimberly M
KM
D000367:Age Factors; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D000841:Anisomycin / Q000494:pharmacology; D048588:Benzoxazines; D003513:Cycloheximide / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism; D066298:In Vitro Techniques; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000494:pharmacology; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D013569:Synapses / Q000502:physiology*; D014966:Xanthenes / Q000494:pharmacology
D000596:Amino Acids; D048588:Benzoxazines; D018691:Excitatory Amino Acid Antagonists; C114624:LY 341495; D009025:Morpholines; D009281:Naphthalenes; D011500:Protein Synthesis Inhibitors; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D018094:Receptors, Metabotropic Glutamate; D014966:Xanthenes; D008734:Methoxyhydroxyphenylglycol; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D000841:Anisomycin; D016291:Dizocilpine Maleate; D003513:Cycloheximide; C109925:AM 281; C010117:3,4-dihydroxyphenylglycol