EC Psychology and Psychiatry

Resting state networks reflect a highly structured, dynamical brain organization that is likely to undergird a diverse and unified suite of behavioral and mental functions. How this organization is generated and what mechanisms are employed to mediate brain functions remained unresolved questions. It is increasingly evident, however, that a key cellular element for constructing these networks is the astrocyte. While traditionally regarded as having a primarily homeostatic role, astrocytes are in fact uniquely qualified to regulate mechanisms of information exchange that are inherent in the structure and dynamics of resting state network operation. Among the chief ways enabling astrocytes to regulate information flow is the formation of compartmentalized, highly dynamic structures targeted to synaptic nodes, known as calcium microdomains, that modulate interneuronal transmission. Microdomains modulate communication between neurons by actively shaping domain specific calcium oscillatory signaling at several levels: morphologically, through activation of actin networks that alter synaptic coverage and local ion concentrations; spatially, by targeting calcium transducers like calcineurin; and molecularly, by regulating calcium influx via calcium transporters and channels, such as the sodium calcium exchanger. Gliotransmission appears to form the basis for the decoding of calcium encoded network influences, contributing to the synchronization of gamma oscillations, resonance based stabilization of noise perturbations, and global network functional activity, among other modulatory mechanisms. Due to the close association of RSNs with brain functioning, they have been identified as fundamental targets for personalized patient care, with the potential to improve the treatment of conditions of the brain and nervous system. Hence, knowledge of how calcium micro-domains regulate information flow in networks can be expected to assist in the development of therapy for cognitive dysfunctions.

Keywords: Calcium Microdomains; Calcium Oscillations; Astrocytes; Resting State Networks; Calcineurin; Perisynaptic Processes; Actin Dynamics; Sodium Calcium Exchanger; Slow Wave; Attractors

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