The Astrocytic Microdomain as a Generative Mechanism for Local Plasticity

Mounting experimental evidence suggests that astrocytes have an active role in synaptic modification. A central premise is that they modify the structure and the function of the neuronal network but the underlying mechanisms for doing so remain elusive. Here, we developed a biophysically constrained 2D compartmental model of an astrocytic microdomain that suggests an explanation for the recently reported functional clustering of synapses. Our model followed the typical geometrical structure of astrocytes, comprising of functionally independent microdomains, and the spatial allocation of their sub-cellular organelles giving rise to (a) fast, process-specific and (b) delayed, microdomain-wide calcium waves. These waves encoded the neuronal activity into their spatial extent and interacted with each other to impose locally restricted synaptic weight modifications constrained in the microdomain. Our results give a possible explanation for the recently reported spatially clustered functional groups in dendritic spines, advocating the astrocytic microdomain as a fundamental learning unit in the brain.