Abstract
In the developing brain, synapses are formed once in excess and trimmed off later (pruning). It is under debate whether the pruning of synapse depends on the synapse's activity or inactivity. Here we show that a long-lasting retardation of synaptic development occurred after the repeated activations of metabotropic glutamate receptor (mGluR) in the dissociated culture of the rat hippocampus, and thereby we suggest that the synaptic pruning depends on the synapse's activity using mGluR. We applied a group I mGluR agonist (DHPG) to the hippocampal neurons of 14 days in vitro, which are still in the process of synaptic development. We found that the culture exposed 3 times to DHPG had a significantly smaller number of synapses in the following weeks, though the number of neurons in the culture was unaffected. This effect was not produced by a single exposure to DHPG and was blocked by a mGluR antagonist (MCPG). This effect was most prominently seen in the proximal dendritic region of glutamatergic neurons. In GABAergic neurons, no significant effect was found in both proximal and distal dendritic regions. These results suggest that repetitive activation of mGluR causes retardation of synaptic development in immature neurons as well as the matured slice culture reported previously, and the retardation shows dendritic region-specificity. [J Physiol Sci. 2007;57 Suppl:S151]