Abstract
At the mossy fiber synapses of hippocampus activity-dependent induction of long-term potentiation (LTP) is dependent on cyclic AMP and protein kinase A (PKA). Activation of PKA turns on inactive synapses to active in hippocampal CA3-CA1 neuronal culture whereas it up-regulates the release probability of active synapses without changes the number of functional synapses in cultured hippocampal interneurons. Here we investigated if new synapses are formed along the mossy fiber axons during PKA activation. Transverse hippocampal slices were made at 400μm from a P14-21 mouse (C57BL/6). The granule cells were identified at the dentate gyrus and labeled with DiI. After incubation for 3 hours at 34°C, the 3-dimensional structure of a mossy fiber was examined at CA3 region under confocal microscopy. We found that the structure of mossy fiber and their terminals little changed in morphology during the experimental period of up to 2 hours. When slices were treated with forskolin (50μM) and 3-isobuthyl-1-methyl xanthine (IBMX, 100μM) for 20 minutes, synapse-like structures were newly formed as early as in 30 minutes. The number of synapse-like structures become about 3 times of the control in 120 minutes and the difference of their densities was statistically significant (P<0.01, Kolmogorov-Smirnov test). The structural changes were almost completely blocked by KT5720 (10μM), a selective PKA inhibitor. It is suggested that the early neurogenesis was induced by cAMP and the subsequent activation of PKA. [Jpn J Physiol 55 Suppl:S143 (2005)]
