Merten, K. | bioRxiv Science

bioRxiv2026

Modeling predicts a biochemical feedback mechanism underlying astrocyte calcium refractory periods

Astrocytes exhibit intracellular calcium fluctuations in response to neuronal activity. Repeated receptor stimulation can induce a transient suppression of calcium signaling--a refractory period--yet the underlying mechanisms and timescales of this phenomenon during behavior remain poorly understood. Here, we present a biophysically grounded computational model of astrocytic calcium signaling that incorporates a novel feedback mechanism mediated by conventional protein kinase C (cPKC) and predicts the refractory phenomenon. Unlike previous models developed in vitro, our model is directly validated using in vivo two-photon calcium imaging data from behaving mice. It closely recapitulates astrocytic calcium dynamics across both time and frequency domains, including the emergence of refractory periods and their negative correlation with inter-stimulus intervals. Simulations further predict the timing of recovery from refractory states, consistent with experimental observations. This work provides a mechanistic explanation for astrocytic refractory behavior and establishes a framework for integrating computational modeling with in vivo functional imaging.

neuroscience↗

bioRxiv2021

Astrocytes encode complex behaviorally relevant information

Astrocytes, glial cells of the central nervous system, help to regulate neural circuit operation and adaptation. They exhibit complex forms of chemical excitation, most prominently calcium transients, evoked by neuromodulator and -transmitter receptor activation1-4. However, whether and how astrocytes contribute to cortical processing of complex behavior remains unknown1. One of the puzzling features of astrocyte calcium transients is the high degree of variability in their spatial and temporal patterns under behaving conditions. Here, we provide mechanistic links between astrocytes activity patterns, molecular signaling, and behavioral cognitive and motor activity variables by employing a visual detection task that allows for in vivo calcium imaging, robust statistical analyses, and machine learning approaches. We show that trial type and performance levels deterministically shape astrocytes spatial and temporal response properties. Astrocytes encode the animals decision, reward, and sensory properties. Our error analysis confirms that astrocytes carry behaviorally relevant information depending on and complementing neuronal coding. We also report that cell-intrinsic mechanisms curb astrocyte calcium activity. Additionally, we show that motor activity-related parameters strongly impact astrocyte responses and must be considered in sensorimotor study designs. Our data inform and constrain current models of astrocytes contribution to complex behavior and brain computation beyond their established homeostatic and metabolic roles.

neuroscience↗