title: Local protein synthesis and GABAB receptors regulate the reversibility of long-term potentiation at murine hippocampal mossy fibre-CA3 synapses.
abstract: Reversal of long-term potentiation (LTP) by long trains of low-frequency stimulation is generally referred to as depotentiation. One of the intriguing aspects of depotentiation is that the magnitude of depotentiation is inversely proportional to the time lag of depotentiation stimulation following LTP induction. Although the mechanisms underlying depotentiation have been widely explored, the factors that regulate the susceptibility of LTP to depotentiation stimulation remain largely unclear. We now report that multiple trains of high-frequency stimulation provide immediate synaptic resistance to depotentiation stimulation at the mossy fibre-CA3 synapses. The synaptic resistance to depotentiation stimulation depends on the amount of synaptic stimulation used to induce LTP; it is prevented by protein synthesis inhibitors and is input specific. In contrast, neither the transection of mossy fibre axons near granule cell somata nor the application of RNA synthesis inhibitors influences synaptic resistance to depotentiation stimulation. We also provide evidence that the induction of depotentiation is regulated by GABA(B) receptors. Application of a GABA(B) receptor antagonist significantly promoted the synaptic resistance to depotentiation stimulation, whereas inhibition of GABA transport delayed the onset of this synaptic resistance. These results suggest that local protein synthesis is required for the development of synaptic resistance to depotentiation stimulation, whereas the activation of GABA(B) receptors promotes the susceptibility to depotentiation stimulation. These two factors may crucially regulate the reversal and stability of long-term information storage.
authors.affiliation: Department of Pharmacology, College of Medicine, National Cheng Kung University, No. 1, Ta-Hsiue Road, Tainan 701, Taiwan.
authors.forename: Chiung-Chun
authors.initials: CC
authors.lastname: Huang
authors.forename: Kuei-Sen
authors.initials: KS
authors.lastname: Hsu
mesh_terms: D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009025:Morpholines / Q000494:pharmacology; D019599:Mossy Fibers, Hippocampal / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000502:physiology*; D018080:Receptors, GABA-B / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
chemical_list: C095804:(+)-(S)-5,5-dimethylmorpholinyl-2-acetic acid; D018755:GABA Agonists; D018756:GABA Antagonists; D009025:Morpholines; D018080:Receptors, GABA-B; D005680:gamma-Aminobutyric Acid; D001418:Baclofen