Emergence of Balanced Cortical Activity via Calcium-Regulated Synaptic Homeostasis

Cortical circuits must stabilize activity while retaining the variability and flexibility essential for computation. This raises a fundamental question: how can excitatory (E) and inhibitory (I) synapses co-adapt through homeostatic plasticity without disrupting network function or relying on fine-tuned parameters? We propose a solution grounded in the multidimensional nature of intracellular calcium signaling, which independently regulates protein synthesis at E and I synapses. By analytically characterizing calcium dynamics driven by spike-train statistics, we show that calciums mean encodes firing rate while its variance reflects spike-time irregularity--two complementary features critical for stable yet flexible spiking. Leveraging this dual signal, we construct a closed-loop model in which inhibitory synapses are regulated by calciums mean and excitatory synapses by its variance through independent pathways. This mechanism preserves irregular spiking and stabilizes firing rates across diverse inputs. Strikingly, it also yields the empirically observed weakening of synaptic strengths with the number of inputs K as [Formula], leading to the spontaneous emergence of balanced excitatory-inhibitory dynamics. These results uncover a calcium-driven regulatory principle linking intracellular signaling to the origin of balanced activity in cortical networks.