Involvements of retrograde signals and glia cells in modulation of synaptic transmissions

点击翻译按钮获取中文摘要

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 CA1 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. To identify the retrograde signal of DSI, we made a paired whole-cell recording from cultured rat hippocampal neurons with inhibitory synaptic connections, and examined the properties of the inhibitory transmission and DSI.In about 60% of pairs, a cannabinoid agonist greatly reduced the release of the inhibitory transmitter GABA from presynaptic terminals. In most of such pairs but not in those insensitive to the agonist, depolarization of postsynaptic neurons and the resultant elevation of intracellular Ca^<2+> concentraton caused transient suppression of inhibitory synaptic currents (DSI), which is mainly due to reduction of GABA release. This DSI was completely blocked by cannabinoid receptor antagonists. The data indicate that endogenous cannabinoids mediate the retrograde signal of DSI.3. These and our previous results support the following hypothesis 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 biosynthesis and release of endogenous cannabinoids. The released cannabinoids bind to presynaptic cannabinoid receptors, and their activation suppresses the transmitter release from inhibitory presynaptic terminals.