Figure 2.

Computational aspects of astrocytic Ca²⁺ signaling. (A) Scheme of IP₃-mediated Ca²⁺-induced Ca²⁺ release in the astrocyte. Calcium and IP₃ signals are controlled by synaptic glutamate through metabotropic glutamate receptor- (mGluR-) PLCβ-mediated IP₃ production (see text for details). (B) IP₃ and Ca²⁺ signals can be envisioned to encode incoming synaptic activity through frequency and amplitude of their oscillations. Astrocytes could thus encode synaptic information either by modulations of the amplitude (AM), the frequency (FM), or both (AFM) of their Ca²⁺ oscillations. (C) Simulated Ca²⁺ and IP₃ patterns in response to sample synaptic glutamate release (Glu) in a model astrocyte (De Pittà et al., 2009a,b) reveals that IP₃ signals could be locked in the AFM-encoding independently of the encoding mode of the associated Ca²⁺ signals. This feature could allow the astrocyte to optimally integrate synaptic stimuli. (D, top) Simulated Ca²⁺ (black trace) and IP₃ (green trace) signals in the same astrocyte model as in (C), and associated rates of IP₃ production (prod.) and degradation (degr.) (middle panels, dashed black lines) in response to two consecutive synaptic glutamate release events (bottom panel, Glu). The analysis of the contributions of different enzymes to IP₃ signaling (solid colored traces; cyan: PLCβ ; pink: PLCδ ; orange: IP-5P; and purple: IP₃-3K) reveals dynamical regulation by Ca²⁺ of different mechanisms of IP₃ production/degradation which could ultimately underlie dynamical regulation of astrocyte processing of synaptic stimuli. (E) Simulated propagation of Ca²⁺ waves in a heterogeneous linear chain composed of both FM (red traces) and AFM (green traces) astrocytes reveals that encoding of synaptic activity (STIMULUS) could change according to cell location along the chain. Adapted from Goldberg et al. (2010).