Astrocytic modulation of cortical synaptic plasticity: Integrating biological knowledge and computational modeling

Poster AbstractsAstrocytes have been shown to control synapse development and function (Allen and Eroglu, 2017). Accumulating evidence also indicate that astrocytes can modulate long-term synaptic transmission and plasticity during postnatal development. However, the biochemical and biophysical mechanisms responsible for these modulations are not fully understood. The mechanisms involved do not only depend on the developmental stage of an animal but also on the brain area and neural circuitry in question. We have analyzed previously published computational models that involve some of these mechanisms (Manninen et al., 2018) and also developed a new computational model of astrocyte-neuron interactions at a layer 4 to layer 2/3 synapse in somatosensory cortex during postnatal development (Manninen et al., 2020). The synapse model is built based on a multitude of data from molecular, biochemical, and electrophysiological experiments in rodent somatosensory cortex. In brief, we showed that 1) endocannabinoids released from the postsynaptic neuron increase astrocytic calcium concentration, similarly to Min and Nevian (2012), 2) the increase in astrocytic calcium concentration can induce exocytosis of glutamate, and 3) the astrocytic glutamate exocytosis activates presynaptic N-methyl-D-aspartate receptors and calcineurin signaling as well as influences synaptic properties. Using the computational model, we were able to make predictions about the dynamics of astrocyte-mediated molecular mechanisms underlying synaptic plasticity and link complex biochemical signaling networks at the presynaptic, postsynaptic, and astrocytic sites to the plasticity changes in a synapse. In the present study, we studied the model to mimic the motility of fine astrocyte processes during synaptic activation, particularly emphasizing long-term plasticity changes (Bernardinelli et al., 2014; Sakert et al., 2017).[...]Lietuvos sveikatos mokslų universitetasTaikomosios informatikos katedraVytauto Didžiojo universiteta