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Optogenetics pp 315-327 | Cite as

Casting Light on the Role of Glial Cells in Brain Function

  • Ko MatsuiEmail author

Abstract

To understand the role of glia in brain function, specific manipulation of glial cell activity is required. Optogenetics was originally introduced as a tool that can manipulate cell membrane potential with light illumination, and its use was mostly limited to neuronal activity manipulation. Depolarization or hyperpolarization by itself did not seem likely to have much effect on glial cell function as these cells largely lack voltage-gated ion channels. A mostly unrecognized fact is that the main cation that crosses the plasma membrane upon light activation of channelrhodopsin-2 or archaerhodopsin is proton. Thus, these optogenetic tools can be regarded as tools that can manipulate intracellular pH. Not only Ca2+ but also H+, Na+ and other intracellular ionic concentrations can dynamically change upon cell activity and can have a profound effect on cell function. Presented here is a study that shows that glutamate release from glia is triggered by intracellular acidification. The released glutamate from glia can have a profound effect on higher-ordered brain functions such as learning and behavior. It is also shown that rampant glial cell activity occurs upon pathological conditions, such as ischemia, and extreme intracellular glial acidification leads to excess glial glutamate release and excitotoxicity. Optogenetics will likely become an essential tool to study the function of cells previously categorized as ‘non-excitable’ cells such as the glia.

Keywords

Glia Astrocyte Glutamate Cerebellum Bergmann glia Purkinje cell Optokinetic response Ischemia Acidosis Excitotoxicity 

References

  1. Barbour B, Häusser M (1997) Intersynaptic diffusion of neurotransmitter. Trends Neurosci 20:377–384PubMedCrossRefGoogle Scholar
  2. Baude A, Nusser Z, Roberts JD et al (1993) The metabotropic glutamate receptor (mGluR1 alpha) is concentrated at perisynaptic membrane of neuronal subpopulations as detected by immunogold reaction. Neuron 11:771–787PubMedCrossRefGoogle Scholar
  3. Beierlein M, Regehr WG (2006) Brief bursts of parallel fiber activity trigger calcium signals in Bergmann glia. J Neurosci 26:6958–6967PubMedCrossRefGoogle Scholar
  4. Beppu K, Sasaki T, Tanaka KF et al (2014) Optogenetic countering of glial acidosis suppresses glial glutamate release and ischemic brain damage. Neuron 81:314–320PubMedCrossRefGoogle Scholar
  5. Berndt A, Yizhar O, Gunaydin LA et al (2009) Bi-stable neural state switches. Nat Neurosci 12:229–234PubMedCrossRefGoogle Scholar
  6. Boyden ES, Zhang F, Bamberg E et al (2005) Millisecond-timescale, genetically targeted optical control of neural activity. Nat Neurosci 8:1263–1268PubMedCrossRefGoogle Scholar
  7. Budisantoso T, Matsui K, Kamasawa N et al (2012) Mechanisms underlying signal filtering at a multisynapse contact. J Neurosci 32:2357–2376PubMedCrossRefGoogle Scholar
  8. Budisantoso T, Harada H, Kamasawa N et al (2013) Evaluation of glutamate concentration transient in the synaptic cleft of the rat calyx of held. J Physiol 591:219–239PubMedCentralPubMedCrossRefGoogle Scholar
  9. Cavelier P, Attwell D (2005) Tonic release of glutamate by a DIDS-sensitive mechanism in rat hippocampal slices. J Physiol 564:397–410PubMedCentralPubMedCrossRefGoogle Scholar
  10. García-Marín V, García-López P, Freire M (2007) Cajal’s contributions to glia research. Trends Neurosci 30:479–487PubMedCrossRefGoogle Scholar
  11. Kanemaru K, Sekiya H, Xu M et al (2014) In vivo visualization of subtle, transient, and local activity of astrocytes using an ultrasensitive Ca(2+) indicator. Cell Rep 8:311–318PubMedCrossRefGoogle Scholar
  12. Kuffler SW, Nicholls JG, Orkand RK (1966) Physiological properties of glial cells in the central nervous system of amphibia. J Neurophysiol 29:768–787PubMedGoogle Scholar
  13. Liu HT, Akita T, Shimizu T et al (2009) Bradykinin-induced astrocyte-neuron signalling: glutamate release is mediated by ROS-activated volume-sensitive outwardly rectifying anion channels. J Physiol 587:2197–2209PubMedCentralPubMedCrossRefGoogle Scholar
  14. Matsui K, Jahr CE (2003) Ectopic release of synaptic vesicles. Neuron 40:1173–1183PubMedCrossRefGoogle Scholar
  15. Matsui K, Jahr CE (2006) Exocytosis unbound. Curr Opin Neurobiol 16:305–311PubMedCrossRefGoogle Scholar
  16. Matsui K, Hosoi N, Tachibana M (1998) Excitatory synaptic transmission in the inner retina: paired recordings of bipolar cells and neurons of the ganglion cell layer. J Neurosci 18:4500–4510PubMedGoogle Scholar
  17. Nishida H, Okabe S (2007) Direct astrocytic contacts regulate local maturation of dendritic spines. J Neurosci 27:331–340PubMedCrossRefGoogle Scholar
  18. Oliet SH, Piet R, Poulain DA (2001) Control of glutamate clearance and synaptic efficacy by glial coverage of neurons. Science 292:923–926PubMedCrossRefGoogle Scholar
  19. Piet R, Jahr CE (2007) Glutamatergic and purinergic receptor-mediated calcium transients in Bergmann glial cells. J Neurosci 27:4027–4035PubMedCentralPubMedCrossRefGoogle Scholar
  20. Sasaki T, Beppu K, Tanaka KF et al (2012) Application of an optogenetic byway for perturbing neuronal activity via glial photostimulation. Proc Natl Acad Sci U S A 109:20720–20725PubMedCentralPubMedCrossRefGoogle Scholar
  21. Schummers J, Yu H, Sur M (2008) Tuned responses of astrocytes and their influence on hemodynamic signals in the visual cortex. Science 320:1638–1643PubMedCrossRefGoogle Scholar
  22. Tanaka KF, Matsui K, Sasaki T et al (2012) Expanding the repertoire of optogenetically targeted cells with an enhanced gene expression system. Cell Rep 2:397–406PubMedCrossRefGoogle Scholar
  23. Thrane AS, Rangroo Thrane V, Zeppenfeld D et al (2012) General anesthesia selectively disrupts astrocyte calcium signaling in the awake mouse cortex. Proc Natl Acad Sci U S A 109:18974–18979PubMedCentralPubMedCrossRefGoogle Scholar
  24. Trussell LO, Zhang S, Raman IM (1993) Desensitization of AMPA receptors upon multiquantal neurotransmitter release. Neuron 10:1185–1196PubMedCrossRefGoogle Scholar
  25. Wake H, Moorhouse AJ, Jinno S et al (2009) Resting microglia directly monitor the functional state of synapses in vivo and determine the fate of ischemic terminals. J Neurosci 29:3974–3980PubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 2015

Authors and Affiliations

  1. 1.Division of Interdisciplinary Medical Science, Center for Neuroscience, Graduate School of MedicineTohoku UniversitySendaiJapan

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