10.4  Synthetic Chromophores and Artificial Sight

We presented a brief review of the three main techniques for imparting optical activity to mammalian cells: (1) light-mediated untethering (or “uncaging”) of chemically modified signaling molecules; (2) chemical modification of ion channels and receptors to render them light-responsive and (3) introduction of light-sensitive proteins into nonphotoactive cells. These are post-electrode prostheses techniques and ideas in laboratory methodology for the study of excitable cells. In principle, they offer the ability to target multiple cells of a specific class simultaneously. External electrodes are limited in their spatial resolution for heterogeneous tissue. Although intracellular electrodes can target specific neurons, they don’t lend themselves to simultaneous targeting of multiple cells of a specific subclass. Moreover, mechanical electrodes are intrusive structures in the context of excitable tissue. Intelligently designed molecular scale activators powered by photon absorption in synthetic chromophores can, in principle, blend into the membranes of excitable tissue with linear dimensions that are compatible with the scale-length and fine structure of the tissue.

The field of synthetic chromophores and its application to artificial sight is motivated by advances that have been made with multielectrode retinal prosthesis arrays. Numerous studies have reported that stimulation of neurons in the visual pathway evokes the perception of light. It is assumed that analogous stimulation at the molecular level will mimic the action of electrodes, with the added advantage of nanoscale resolution and auto-power by the photons that trigger the neural activity. There is, at present, no clinical data to support this assumption. Moreover, in order for synthetic chromophores to be relevant to real-world applications they need to be stable or easily rejuvenated and operate at ambient wavelengths and light intensities, either on their own or in conjunction with optoelectronic signal conditioning devices. These are challenging areas of research and biomedical engineering that are currently in early stages of development.

Acknowledgments  The author thanks M. S. Humayun, J. D. Weiland, T. Kuritz, I. Lee, C. P. Pennisi, C. A. Sanders, B. R. Evans, and H. M. O’Neill for advice, support and discussions. This work was supported by the Office of Biological and Environmental Research, U.S. Department of Energy. Oak Ridge National Laboratory is managed by UT-Battelle, LLC for the U. S. Department of Energy under Contract No. DE-AC05-00OR22725.

References

1.Balasubramanian D, Subramani S, Kumar C (1975), Modification of a model membrane structure by embedded photochrome. Nature, 254(5497): p. 252–4.

2.Banghart M, Borges K, Isacoff E, et al. (2004), Light-activated ion channels for remote ­control of neuronal firing. Nat Neurosci, 7(12): p. 1381–6.

3.Boyden ES, Zhang F, Bamberg E, et al. (2005), Millisecond-timescale, genetically targeted optical control of neural activity. Nat Neurosci, 8(9): p. 1263–8.

28. Pieroni O, Houben JL, Fissi A, Costantino P (1980), Reversible conformational-changes induced by light in poly(l-glutamic acid) with photochromic side-chains. J Am Chem Soc,

102(18): p. 5913–5.

29. Sisido M, Ishikawa Y, Itoh K, Tazuke S (1991), Helically arranged azobenzene chromophores along a polypeptide-chain. 1. synthesis and circular-dichroism. Macromolecules, 24(14): p. 3993–8.

30. Standaert RF, Park SB (2006), Abc amino acids: design, synthesis, and properties of new photoelastic amino acids. J Org Chem, 71(21): p. 7952–66.

31. Stryer L (1995), Biochemistry, 4 ed. New York: W. H. Freeman and Company. p. 1064.

32. Volgraf M, Gorostiza P, Numano R, et al. (2006), Allosteric control of an ionotropic glutamate receptor with an optical switch. Nat Chem Biol, 2(1): p. 47–52.

33. Wang SS, Khiroug L, Augustine GJ (2000), Quantification of spread of cerebellar long-term depression with chemical two-photon uncaging of glutamate. Proc Natl Acad Sci USA,

97(15): p. 8635–40.

34. Wilcox M, Viola RW, Johnson KW, et al. (1990), Synthesis of photolabile precursors of amino-acid neurotransmitters. J Org Chem, 55(5): p. 1585–9.

35. Willner I, Rubin S (1996), Control of the structure and functions of biomaterials by light.

Angew Chem Int Ed Engl, 35(4): p. 367–85.

36. Yager KG, Barrett CJ (2006), Novel photo-switching using azobenzene functional materials.

J Photochem Photobiol A Chem, 182(3): p. 250–61.

37. Zemelman BV, Nesnas N, Lee GA, Miesenbock G (2003), Photochemical gating of heterologous ion channels: remote control over genetically designated populations of neurons. Proc Natl Acad Sci USA, 100(3): p. 1352–7.

38. Zhang F, Wang LP, Boyden ES, Deisseroth K (2006), Channelrhodopsin-2 and optical control of excitable cells. Nat Methods, 3(10): p. 785–92.

39. Lin B, Koizumi A, Tanaka N, Panda S, Masland RH (2008), Restoration of visual function in retinal degeneration mice by ectopic expression of melanopsin. Proc Natl Acad Sci USA

105(41): 16009–14.

40. Partridge JC, Douglas RH (1995) Far-red sensitivity of dragon fish. Nature 375: p. 21–2. 41. Douglas RH, Partridge JC, Dulai K, Hunt D, Mullineaux CW, Tauber AY, Hynninen PH

(1998), Dragon fish see using chlorophyll. Nature, 393: p. 423–4.

42. Washington I, Zhou J, Jockusch S, Turro NJ, Nakanishi K, Sparrow JR (2007), Chlorophyll derivatives as visual pigments for super vision in the red. Photochem Photobiol Sci, 7: p. 775–9.

Chapter 11

Biophysics/ Engineering of Cortical Electrodes

Philip R. Troyk

Abstract  This chapter provides a description of how microelectrodes are used to form an artificial interface to the cortex. Microelectrodes inserted into the cortex are called “intracortical electrodes” and are anticipated for use in cortical visual prostheses. Owing to the nature of the cortical environment, the design and use of these electrodes pose challenges for the clinical deployment of cortical prostheses. The combined effects of electrode charge injection and effects of the in vivo environment are discussed.

Abbreviations

P.R. Troyk (*)

Department of Biomedical Engineering,

Pritzker Institute of Biomedical Science and Engineering, Illinois Institute of Technology, 3255 S. Dearborn, WH 314, Chicago, IL 60616, USA

e-mail: troyk@iit.edu