Glia Regulate the Development, Function, and Plasticity of the Visual System From Retina to Cortex.

Visual experience is mediated through a relay of finely-tuned neural circuits extending from the retina, to retinorecipient nuclei in the midbrain and thalamus, to the cortex which work together to translate light information entering our eyes into a complex and dynamic spatio-temporal representation of the world. While the experience-dependent developmental refinement and mature function of neurons in each major stage of the vertebrate visual system have been extensively characterized, the contributions of the glial cells populating each region are comparatively understudied despite important findings demonstrating that they mediate crucial processes related to the development, function, and plasticity of the system. In this article we review the mechanisms for neuron-glia communication throughout the vertebrate visual system, as well as functional roles attributed to astrocytes and microglia in visual system development and processing. We will also discuss important aspects of glial function that remain unclear, integrating the knowns and unknowns about glia in the visual system to advance new hypotheses to guide future experimental work.

Sodium-calcium exchanger mediates sensory-evoked glial calcium transients in the developing retinotectal system.

Various types of sensory stimuli have been shown to induce Ca2+ elevations in glia. However, a mechanistic understanding of the signaling pathways mediating sensory-evoked activity in glia in intact animals is still emerging. During early development of the Xenopus laevis visual system, radial astrocytes in the optic tectum are highly responsive to sensory stimulation. Ca2+ transients occur spontaneously in radial astrocytes at rest and are abolished by silencing neuronal activity with tetrodotoxin. Visual stimulation drives temporally correlated increases in the activity patterns of neighboring radial astrocytes. Following blockade of all glutamate receptors (gluRs), visually evoked Ca2+ activity in radial astrocytes persists, while neuronal activity is suppressed. The additional blockade of either glu transporters or sodium-calcium exchangers (NCX) abolishes visually evoked responses in glia. Finally, we demonstrate that blockade of NCX alone is sufficient to prevent visually evoked responses in radial astrocytes, highlighting a pivotal role for NCX in glia during development.

Neuron-astrocyte networking: astrocytes orchestrate and respond to changes in neuronal network activity across brain states and behaviors.

Astrocytes are known to play many important roles in brain function. However, research underscoring the extent to which astrocytes modulate neuronal activity is still underway. Here we review the latest evidence regarding the contribution of astrocytes to neuronal oscillations across the brain, with a specific focus on how astrocytes respond to changes in brain state (e.g., sleep, arousal, stress). We then discuss the general mechanisms by which astrocytes signal to neurons to modulate neuronal activity, ultimately driving changes in behavior, followed by a discussion of how astrocytes contribute to respiratory rhythms in the medulla. Finally, we contemplate the possibility that brain stem astrocytes could modulate brainwide oscillations by communicating the status of oxygenation to higher cortical areas.