Astrocytes neural network multiscale response to extracellular sensing cues
Abstract
Evidence from the past 40 years revealed that the capability of the brain to collect, elaborate and convey information is not relying only on neurons. Indeed, glial cells called astrocytes tightly control brain homeostatic equilibrium, but also cognitive functions, by sensing, active integration and actuation of brain information flow. Specifically, transmembrane proteins forming ion channels, water channels, gap junction and transporters in astrocytes allow ions and water dynamics, critically implicated in cognitive functions, at a multiscale. In this respect, the proponent team proposed to broaden neurocentric view of brain function and showcased the use of advanced (nano)biomaterials, devices, and biophysical approaches to provide mechanistic insight into astrocytes structure and function. Within the context of AFOSR-Biophysics Programm funded project, we found that astrocytes could sense changes in the chemophysical properties of the extracellular environment and responds to physical stimuli such as electric field and electromagnetic waves by actuating ion and water dynamics across the plasma membrane, actin dynamics, and intracellular variation of calcium concentrations ([Ca2+]i). However, the emergence and impact of these dynamics at network level and in the communication between neurons and astrocytes have not been elucidated. This lack of knowledge hampers the translation of the achieved results in computational models and artificial neural networks, that so far have been focused on neurons and neuron action potential. On this basis, with the overall aim to understand how astrocytes-neurons interaction participate to multiscale-multimodal neural networks to process information and to respond to environmental challenges, we herein propose to evaluate the response of astrocytes ion channels, calcium signalling and water dynamics to different chemo-physical properties of the extracellular environment and to physical stimuli. Chemo-physical properties of extracellular matrix will be tightly controlled with ad-hoc designed biomaterials tailored to engineer 2D and 3D neural network cell culture. Physical stimuli will be applied by using electromagnetic wave through light exposure or Low dose Microwave (Mw). The analyses will be performed in astrocyte embedded in a complex neural network with neurons (namely Neural Stem Cells). The collected data will serve as a layout to support the collaboration with Prof W. Losert s Team at the University of Maryland (UMD). UMD will use the data to generate a dataset for a testbed for a computational approach, where the response of astrocytes to stress Sensing Neural Network performance changes under physical stress. Our primary objective is to establish connections between fundamental cellular and molecular activities within astrocytes, which impact communication between astrocytes and neurons both in normal physiological conditions and when subjected to chemical or physical disruptions. We aim to extend these findings to understand higher-level network functions, thereby promoting the idea of information exchange within the brain from a perspective that encompasses not only neurons but also the broader neuroglial framework. The results of ASTROSENSE might open unprecedented insight into neural network signatures underpinning brain cognitive function and human performance. Such model could be also foundational to generate knowledge and possibly predict the response of the brain to chemical and physical stress from the extracellular environment.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Feb 06, 2025
- Source ID
- FA95502510001
Entities
People
- Valentina Benfenati
Organizations
- Air Force Office of Scientific Research
- United States Air Force