Host: The Physiological Society of Japan
Neurotrophic factors are a family of diffusible intercellular messengers and indicated to be involved in differentiation, development and survival of neurons in nervous systems. In the present study, we demonstrate an involvement of brain-derived neurotrophic factor (BDNF) in functional maintenance of excitatory synapses in mature cerebellum.The original interest of the study is to examine functional roles of inositol 1,4,5-trisphosphate (IP3) signaling in glutamatergic synapses in the mature cerebellum. We first examined changes in synaptic functions after a chronic in vivo suppression of IP3 level in cerebellar Purkinje cells (PCs) by overexpressing exogenous IP3 5-phosphatase (5-Ppase), which selectively hydrolyzes IP3. The suppression of IP3 production in PCs for 1 days resulted in the decrease in the strength of parallel fiber (PF) -PC synapses, accompanied with the decrease in the probability of transmitter release from PFs. Because IP3 5-Ppase was specifically expressed in PCs, postsynaptic site of PF synapse, the observation indicates an involvement of retrograde signaling in the functional maintenance of PF synapse. Among many candidate factors involved in the retrograde signaling, application of exogenous BDNF rescued the attenuation of synaptic function in IP3 5-Ppase expressing PCs. Furthermore, chronic neutralization of endogenous BDNF with function-blocking antiserum not only inhibited transmitter release from PFs but also occluded the effect of IP3 5-Pase. These results indicate that IP3-BDNF signaling maintains function of PF-PC synapse in the mature cerebellum. [J Physiol Sci. 2008;58 Suppl:S17]
