Roles of retrograde messengers at inhibitory synapses
Grant-in-Aid for Scientific Research (C)
|Allocation Type||Single-year Grants|
|Research Institution||Kanazawa University|
OHNO-SHOSAKU Takako Kanazawa University, Fac.of Med., assistant professor, 医学部, 助教授 (60179025)
|Project Period (FY)
1997 – 1998
Completed(Fiscal Year 1998)
|Budget Amount *help
¥2,400,000 (Direct Cost : ¥2,400,000)
Fiscal Year 1998 : ¥700,000 (Direct Cost : ¥700,000)
Fiscal Year 1997 : ¥1,700,000 (Direct Cost : ¥1,700,000)
|Keywords||Hippocampus / Inhibitory synaptic transmission / Retrograde messenger / Synaptic plasticity / Calcium ion / Glutamic acid / ボルボルエステル|
1.Recent studies have suggested that retrograde messengers might play an important role in synaptic modulations and plasticity in the central nervous system. In the hippocampus, depolarization of a CAl pyramidal neuron elicits a transient suppression of inhibitory synaptic inputs to the depolarized cell. This phenomenon is referred to as DSI (depolarization-induced suppression of inhibition). The studies with hippocampal slices demonstrated that a retrograde messenger should be involved in DSI.
2.In the present study, we examined mechanisms of DSI and the role of the retrograde messenger in DSI with cultured rat hippocampal neurons. The results and conclusions are as follows.
(1)A pair of cultured hippocampal neurons can exhibit DSI similar to that previously reported to occur in hippocampal slices.
(2)Extracellular Ca^<2+> ions are prerequisite for the induction of DSI.
(3)The inhibition of voltage-dependent Ca^<2+> channels suppresses DSI.
(4)The release of the inhibitory transmitter from presynaptic terminals is suppressed during DSI.
(5)The protein kinase C activator (phorbol ester) suppresses DSI.
(6)The inhibition of CaM kinase II suppresses DSI.
(7)DSI can propagate from the synapses on a depolarized neuron to those on a non-depolarized neuron.
3.These results support the following hypotheses accounting for DSI.Depolarization of a postsynaptic neuron elicits an increase in postsynaptic intracellular Ca^<2+> concentration by activating Ca^<2+> channels, which in turn triggers the release of retrograde messenger via CaM kinase Il-dependent processes. The activation of presynaptic receptors by the retrograde messenger induces suppression of inhibitory transmission via phobol ester-sensitive processes.
Research Products (16results)