Spatial synaptic modulation through IP3 diffusion triggered by ECB: a computational study with an astrocyte-neurons...

Recently, functional interactions between neurons and astrocytes have been steadily clarified. In particular, the effects of presynaptic depolarization-induced suppression of excitation (DSE) through endocannabinoid (ECB) and endocannabinoids-mediated synaptic potentiation (eSP) by an astrocyte have been used as an evidence of global heterosynaptic modulation. However, the mechanism of occurrence of spatial modulation in a neural network remains unknown. Although the Ca²⁺ density in astrocytes is strongly related to eSP through ECB, the mechanism of the rise in the ECB receptor in Ca²⁺ remains unclear. Since Ca²⁺ is closely related to inositol-1,4,5-trisphosphate (IP₃), it is believed that the released IP₃ affects Ca²⁺ in astrocytes that receive ECB. Therefore, this study approximately showed the spatial distribution of DSE or eSP with astrocyte-neuron computational models, assuming that the IP₃ caused by ECB is transmitted in an astrocyte. The results showed doughnut-shaped DSE, eSP, and DSE regions from the central ECB released points to the surroundings. They suggested that IP₃ diffusion plays an important role in mediating this synaptic modulation.