The mechanism of hetero-synaptic interaction based on spatiotemporal intracellular calcium dynamics.

Frontiers in Systems Neuroscience

卷:8

Daiki Futagi¹ 

[1] Ritsumeikan University;

关键词: Calcium Signaling;    synaptic plasticity;    NMDA receptor;    ryanodine Receptor;    simulation models;    voltage-dependent calcium channels;   

DOI  :  10.3389/conf.fnsys.2014.05.00009

来源: DOAJ

【 摘 要 】

In recent physiological experiments focusing on synaptic plasticity, it is shown that synaptic modifications induced at one synapse are accompanied by hetero-synaptic changes at neighbor sites (Bi, 2002). These evidences imply that the hetero-synaptic interaction plays an important role in reconfiguration of synaptic connections to form and maintain functional neural circuits (Takahashi et al., 2012). Although the mechanism of the interaction is still unclear, some physiological studies suggest that the hetero-synaptic interaction could be caused by propagation of intracellular calcium signals (Nishiyama et al., 2000). Concretely, a spike-triggered calcium increase initiates calcium ion propagation along a dendrite through activation of molecular processes at neighboring sites. Here we hypothesized that the mechanism of the hetero-synaptic interaction was based on the intracellular calcium signaling, which is regulated by interactions between NMDA receptors (NMDARs), voltage-dependent calcium channels (VDCCs) and Ryanodine receptors (RyRs) on endoplasmic reticulum (ER). To assess realizability of the hypothesized interaction mechanism, we simulated intracellular calcium dynamics at a cellular level, using the computational model that integrated the model of intracellular calcium dynamics (Keizer and Levine, 1996) and the multi-compartment neuron model (Poirazi et al., 2003). Using the proposed computational model, we induced calcium influxes at a local site in postsynaptic dendrite by controlling the spike timings of pre- and postsynaptic neurons. As a result, synchronized calcium influxes through NMDARs and VDCCs caused calcium release from ER. According to the phase plane analysis, RyR-mediated calcium release occurred when the calcium concentration in cytoplasm sufficiently increased under the condition of a high calcium concentration in ER. An NMDAR-mediated calcium influx was slow and persistent, consequently responsible for maintaining a high calcium concentration in ER. In contrast, a VDCC-mediated calcium influx was rapid and transient so that it contributed to rapid increase in calcium the concentration in cytoplasm. Taken together, it was found that calcium concentration exhibited a supralinear increase when a presynaptic spike preceded a postsynaptic one. The calcium ions released from ER diffused along cytoplasm and then activated RyRs at neighboring sites. Thus cascades of RyR activation along a dendrite contributed to propagation of calcium pulses. The range of calcium propagation was 10-100 micrometers and depended on dendritic locations because the spatial distribution of VDCC expression was not homogeneous along a dendrite. According to the experimental evidences that the outcome of synaptic plasticity depends on postsynaptic calcium concentration, it was suggested that the RyR-regulated calcium propagation could serve as the mechanism of the hetero-synaptic interaction.

【 授权许可】

Unknown