Glial cell regulation of neuronal activity and blood flow in the retina by release of gliotransmitters

Newman, Eric A.

doi:10.1098/rstb.2014.0195

Cited by 161 publications

(129 citation statements)

References 40 publications

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“…Release of steroids and even cholesterol from astrocytes has additionally attracted attention that glial cells might exert endocrine functions [2,3], leading to regulation of, for instance, glutamate transporters in neurons [4]. Likewise, Mü ller cells in the retina control photoreceptor function and blood flow by the release of various vasoactive agents [5]. In addition, they may act as source of polyamines [6], which may modulate neuronal function at a fast time scale by modulating the activity of a variety of ion channels, including inactivation of Na þ channels [7].…”

Section: Introductionmentioning

confidence: 99%

Regulation of neuronal excitability by release of proteins from glial cells

Igelhorst

Niederkinkhaus

Karus

et al. 2015

Phil. Trans. R. Soc. B

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Effects of glial cells on electrical isolation and shaping of synaptic transmission between neurons have been extensively studied. Here we present evidence that the release of proteins from astrocytes as well as microglia may regulate voltage-activated Na þ currents in neurons, thereby increasing excitability and speed of transmission in neurons kept at distance from each other by specialized glial cells. As a first example, we show that basic fibroblast growth factor and neurotrophin-3, which are released from astrocytes by exposure to thyroid hormone, influence each other to enhance Na þ current density in cultured hippocampal neurons. As a second example, we show that the presence of microglia in hippocampal cultures can upregulate Na þ current density. The effect can be boosted by lipopolysaccharides, bacterial membrane-derived stimulators of microglial activation. Comparable effects are induced by the exposure of neuron-enriched hippocampal cultures to tumour necrosis factor-a, which is released from stimulated microglia. Taken together, our findings suggest that release of proteins from various types of glial cells can alter neuronal excitability over a time course of several days. This explains changes in neuronal excitability occurring in states of thyroid hormone imbalance and possibly also in seizures triggered by infectious diseases.

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Section: Introductionmentioning

confidence: 99%

Regulation of neuronal excitability by release of proteins from glial cells

Igelhorst

Niederkinkhaus

Karus

et al. 2015

Phil. Trans. R. Soc. B

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“…Other cell classes, glial and vascular cells in particular, have been viewed as secondary components of the CNS, supporting neurons structurally and metabolically without actively influencing neural function. During the last few decades, however, it has become clear that this is not the case, and that these supporting cells, in fact, play crucial active roles [9]. Though our understanding of the individual components of the nervous system has been increasing exponentially, failing to consider fully the interactions between these diverse elements inherently limits our perspective on the physiology and pathophysiology of the CNS, in turn limiting our ability to translate these findings to clinical applications.…”

Section: The Neurovascular Unit: a Fundamental Circuitmentioning

confidence: 99%

Leveraging Optogenetic-Based Neurovascular Circuit Characterization for Repair

2016

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Optogenetic techniques are a powerful tool for determining the role of individual functional components within complex neural circuits. By genetically targeting specific cell types, neural mechanisms can be actively manipulated to gain a better understanding of their origin and function, both in health and disease. The potential of optogenetics is not limited to answering biological questions, as it is also a promising therapeutic approach for neurological diseases. An important prerequisite for this approach is to have an identified target with a uniquely defined role within a given neural circuit. Here, we examine the retinal neurovascular unit, a circuit that incorporates neurons and vascular cells to control blood flow in the retina. We highlight the role of a specific cell type, the cholinergic amacrine cell, in modulating vascular cells, and demonstrate how this can be targeted and controlled with optogenetics. A better understanding of these mechanisms will not only extend our understanding of neurovascular interactions in the brain, but ultimately may also provide new targets to treat vision loss in a variety of retinal diseases.

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“…Activity of nerve cells, irrespective of their transmitters, depolarizes glial cells, which in turn generate a local increase in blood flow just where it is most needed. Again, in the retina, ganglion cells, which provide the output from the retina, are inhibited by the release of ATP from Mü ller cells, the main type of retinal glial cell [39]. Of particular interest is that retinal glial cells release vasoactive agents as well as ATP.…”

Section: (C) Effects Of Extrasynaptic Transmission On Functional Actimentioning

confidence: 99%