Activation of microglia by neuronal activity: Results from a new in vitro paradigm based on neuronal-silicon interfacing technology

Cognition and behavior primarily arise from the communication that occurs between brain cells. By using photoconductive stimulation to trigger localized regions of neuronal action potentials and astrocyte Ca2+ waves in dissociated rat hippocampal cultures, we can directly study microglia behavior in response to physiological and pathological levels of activity. Connections between neurons can be modified by microglia, which regulate gap junctions and synapses through secretion of proteins such as cytokines, proteases and neurotrophic factors. Activated microglia participate in bidirectional communication with the excitable tissues that they support. Through feedback from the many ion channels and surface receptors they express, microglia are informed of neuronal and astrocytic activity that may indicate disruption in the homeostasis of the CNS. Such disturbances alert microglia to locations of such activity and promote their transformation into a reactive state, in which they perform adaptive functions that can be either neuroprotective, neurotoxic, or neuromodulatory. Under physiological conditions, normal brain activity has the effect of suppressing microglia inflammatory responses. This report summarizes available data about the interaction of microglia and brain activity and presents a new in vitro paradigm to study the mechanisms involved. We propose that photoconductive stimulation is a powerful tool for studying the cellular and molecular mechanisms underlying the dynamic interactions between neurons, astrocytes and microglia.