Abstract
The combination of optogenetic interventions and behavioral assays allows investigating causal effects of neural activity with unprecedented spatial and temporal resolution. However, utilizing the technique also requires special considerations in designing the experimental procedures and assigning controls. In this chapter, we give an overview of the requirements for behavioral-optogenetic experiments in rodents and nonhuman primates. Special emphasis is given to correct assignments of controls and how to avoid artifacts.
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References
Boyden ES, Zhang F, Bamberg E, Nagel G, Deisseroth K (2005) Millisecond-timescale, genetically targeted optical control of neural activity. Nat Neurosci 8:1263–1268. doi:10.1038/nn1525
Aravanis AM, Wang L-P, Zhang F, Meltzer LA, Mogri MZ, Schneider MB, Deisseroth K (2007) An optical neural interface: in vivo control of rodent motor cortex with integrated fiberoptic and optogenetic technology. J Neural Eng 4:S143. doi:10.1088/1741-2560/4/3/S02
Zeng H, Madisen L (2012) Mouse transgenic approaches in optogenetics. Prog Brain Res 196:193–213. doi:10.1016/B978-0-444-59426-6.00010-0
Witten IB, Steinberg EE, Lee SY, Davidson TJ, Zalocusky KA, Brodsky M, Yizhar O, Cho SL, Gong S, Ramakrishnan C, Stuber GD, Tye KM, Janak PH, Deisseroth K (2011) Recombinase-driver rat lines: tools, techniques, and optogenetic application to dopamine-mediated reinforcement. Neuron 72:721–733. doi:10.1016/j.neuron.2011.10.028
Niu Y, Shen B, Cui Y, Chen Y, Wang J, Wang L, Kang Y, Zhao X, Si W, Li W, Xiang AP, Zhou J, Guo X, Bi Y, Si C, Hu B, Dong G, Wang H, Zhou Z, Li T, Tan T, Pu X, Wang F, Ji S, Zhou Q, Huang X, Ji W, Sha J (2014) Generation of gene-modified cynomolgus monkey via Cas9/RNA-mediated gene targeting in one-cell embryos. Cell 156:836–843. doi:10.1016/j.cell.2014.01.027
Sasaki E, Suemizu H, Shimada A, Hanazawa K, Oiwa R, Kamioka M, Tomioka I, Sotomaru Y, Hirakawa R, Eto T, Shiozawa S, Maeda T, Ito M, Ito R, Kito C, Yagihashi C, Kawai K, Miyoshi H, Tanioka Y, Tamaoki N, Habu S, Okano H, Nomura T (2009) Generation of transgenic non-human primates with germline transmission. Nature 459:523–527. doi:10.1038/nature08090
Li N, Chen T-W, Guo ZV, Gerfen CR, Svoboda K (2015) A motor cortex circuit for motor planning and movement. Nature 519:51–56. doi:10.1038/nature14178
Kuhlman SJ, Huang ZJ (2008) High-resolution labeling and functional manipulation of specific neuron types in mouse brain by cre-activated viral gene expression. PLoS One 3:e2005. doi:10.1371/journal.pone.0002005
Gradinaru V, Zhang F, Ramakrishnan C, Mattis J, Prakash R, Diester I, Goshen I, Thompson KR, Deisseroth K (2010) Molecular and cellular approaches for diversifying and extending optogenetics. Cell 141:154–165. doi:10.1016/j.cell.2010.02.037
Callaway EM (2008) Transneuronal circuit tracing with neurotropic viruses. Curr Opin Neurobiol 18:617–623. doi:10.1016/j.conb.2009.03.007
Hnasko TS, Perez FA, Scouras AD, Stoll EA, Gale SD, Luquet S, Phillips PEM, Kremer EJ, Palmiter RD (2006) Cre recombinase-mediated restoration of nigrostriatal dopamine in dopamine-deficient mice reverses hypophagia and bradykinesia. Proc Natl Acad Sci 103:8858–8863. doi:10.1073/pnas.0603081103
Judkewitz B, Rizzi M, Kitamura K, Häusser M (2009) Targeted single-cell electroporation of mammalian neurons in vivo. Nat Protoc 4:862–869. doi:10.1038/nprot.2009.56
Dugué GP, Akemann W, Knöpfel T (2012) A comprehensive concept of optogenetics. Prog Brain Res 196:1–28. doi:10.1016/B978-0-444-59426-6.00001-X
Miyashita T, Shao YR, Chung J, Pourzia O, Feldman DE (2013) Long-term channelrhodopsin-2 (ChR2) expression can induce abnormal axonal morphology and targeting in cerebral cortex. Front Neural Circuits 7(8). doi:10.3389/fncir.2013.00008
Schwarz C, Hentschke H, Butovas S, Haiss F, Stüttgen MC, Gerdjikov TV, Bergner CG, Waiblinger C (2010) The head-fixed behaving rat—procedures and pitfalls. Somatosens Mot Res 27:131–148. doi:10.3109/08990220.2010.513111
Warden MR, Selimbeyoglu A, Mirzabekov JJ, Lo M, Thompson KR, Kim S-Y, Adhikari A, Tye KM, Frank LM, Deisseroth K (2012) A prefrontal cortex-brainstem neuronal projection that controls response to behavioural challenge. Nature 492:428–432. doi:10.1038/nature11617
Vite CH, Passini MA, Haskins ME, Wolfe JH (2003) Adeno-associated virus vector-mediated transduction in the cat brain. Gene Ther 10:1874–1881. doi:10.1038/sj.gt.3302087
Zhang F, Gradinaru V, Adamantidis AR, Durand R, Airan RD, de Lecea L, Deisseroth K (2010) Optogenetic interrogation of neural circuits: technology for probing mammalian brain structures. Nat Protoc 5:439–456. doi:10.1038/nprot.2009.226
Yizhar O, Fenno LE, Davidson TJ, Mogri M, Deisseroth K (2011) Optogenetics in neural systems. Neuron 71:9–34. doi:10.1016/j.neuron.2011.06.004
Hardung S, Epple R, Jäckel Z, Eriksson D, Uran C, Senn V, Gibor L, Yizhar O, Diester I (2017) A functional gradient in the rodent prefrontal cortex supports behavioral inhibition. Curr Biol 27:549–555. doi:10.1016/j.cub.2016.12.052
Noudoost B, Moore T (2011) A reliable microinjectrode system for use in behaving monkeys. J Neurosci Methods 194:218–223. doi:10.1016/j.jneumeth.2010.10.009
Diester I, Kaufman MT, Mogri M, Pashaie R, Goo W, Yizhar O, Ramakrishnan C, Deisseroth K, Shenoy KV (2011) An optogenetic toolbox designed for primates. Nat Neurosci 14:387–397. doi:10.1038/nn.2749
Ozden I, Wang J, Lu Y, May T, Lee J, Goo W, O’Shea DJ, Kalanithi P, Diester I, Diagne M, Deisseroth K, Shenoy KV, Nurmikko AV (2013) A coaxial optrode as multifunction write-read probe for optogenetic studies in non-human primates. J Neurosci Methods 219:142–154. doi:10.1016/j.jneumeth.2013.06.011
Lee J, Ozden I, Song Y-K, Nurmikko AV (2015) Transparent intracortical microprobe array for simultaneous spatiotemporal optical stimulation and multichannel electrical recording. Nat Methods 12:1157–1162. doi:10.1038/nmeth.3620
Yaroslavsky AN, Schulze PC, Yaroslavsky IV, Schober R, Ulrich F, Schwarzmaier H-J (2002) Optical properties of selected native and coagulated human brain tissues in vitro in the visible and near infrared spectral range. Phys Med Biol 47:2059. doi:10.1088/0031-9155/47/12/305
Szél Á, Röhlich P (1992) Two cone types of rat retina detected by anti-visual pigment antibodies. Exp Eye Res 55:47–52. doi:10.1016/0014-4835(92)90090-F
Han X, Qian X, Bernstein JG, Zhou H, Franzesi GT, Stern P, Bronson RT, Graybiel AM, Desimone R, Boyden ES (2009) Millisecond-timescale optical control of neural dynamics in the nonhuman primate brain. Neuron 62:191–198. doi:10.1016/j.neuron.2009.03.011
Cardin J (2012) Integrated optogenetic and electrophysiological dissection of local cortical circuits in vivo. In: Fellin T, Halassa M (eds) Neuronal Netw. Anal. Humana Press, Totowa, NJ, pp 339–355
Berndt A, Schoenenberger P, Mattis J, Tye KM, Deisseroth K, Hegemann P, Oertner TG (2011) High-efficiency channelrhodopsins for fast neuronal stimulation at low light levels. Proc Natl Acad Sci 108:7595–7600. doi:10.1073/pnas.1017210108
Gradinaru V, Thompson KR, Zhang F, Mogri M, Kay K, Schneider MB, Deisseroth K (2007) Targeting and readout strategies for fast optical neural control in vitro and in vivo. J Neurosci 27:14231–14238. doi:10.1523/JNEUROSCI.3578-07.2007
Kravitz AV, Freeze BS, Parker PRL, Kay K, Thwin MT, Deisseroth K, Kreitzer AC (2010) Regulation of parkinsonian motor behaviours by optogenetic control of basal ganglia circuitry. Nature 466:622–626. doi:10.1038/nature09159
Jin X, Tecuapetla F, Costa RM (2014) Basal ganglia subcircuits distinctively encode the parsing and concatenation of action sequences. Nat Neurosci 17:423–430. doi:10.1038/nn.3632
Guo ZV, Li N, Huber D, Ophir E, Gutnisky D, Ting JT, Feng G, Svoboda K (2014) Flow of cortical activity underlying a tactile decision in mice. Neuron 81:179–194. doi:10.1016/j.neuron.2013.10.020
Ohayon S, Grimaldi P, Schweers N, Tsao DY (2013) Saccade modulation by optical and electrical stimulation in the macaque frontal eye field. J Neurosci 33:16684–16697. doi:10.1523/JNEUROSCI.2675-13.2013
O’Shea DJ, Goo W, Diester I, Kalanithi P, Yizhar O, Ramakrishnan C, Deisseroth K, Shenoy KV (2011) Optogenetic control of excitatory neurons via a red-shifted opsin in primate premotor cortex. Program No. 306.11. Neuroscience meeting planner. Society for Neuroscience, Washington, DC (online)
Gerits A, Farivar R, Rosen BR, Wald LL, Boyden ES, Vanduffel W (2012) Optogenetically induced behavioral and functional network changes in primates. Curr Biol 22:1722–1726. doi:10.1016/j.cub.2012.07.023
Cavanaugh J, Monosov IE, McAlonan K, Berman R, Smith MK, Cao V, Wang KH, Boyden ES, Wurtz RH (2012) Optogenetic inactivation modifies monkey visuomotor behavior. Neuron 76:901–907. doi:10.1016/j.neuron.2012.10.016
Gilja V, Chestek CA, Diester I, Henderson JM, Deisseroth K, Shenoy KV (2011) Challenges and opportunities for next-generation intracortically based neural prostheses. IEEE Trans Biomed Eng 58:1891–1899. doi:10.1109/TBME.2011.2107553
Grosenick L, Marshel JH, Deisseroth K (2015) Closed-loop and activity-guided optogenetic control. Neuron 86:106–139. doi:10.1016/j.neuron.2015.03.034
Shenoy KV, Carmena JM (2014) Combining decoder design and neural adaptation in brain-machine interfaces. Neuron 84:665–680. doi:10.1016/j.neuron.2014.08.038
Paz JT, Davidson TJ, Frechette ES, Delord B, Parada I, Peng K, Deisseroth K, Huguenard JR (2013) Closed-loop optogenetic control of thalamus as a tool for interrupting seizures after cortical injury. Nat Neurosci 16:64–70. doi:10.1038/nn.3269
Siegle JH, Wilson MA (2014) Enhancement of encoding and retrieval functions through theta phase-specific manipulation of hippocampus. eLife 3:e03061. doi:10.7554/eLife.03061
Newman JP, Fong M, Millard DC, Whitmire CJ, Stanley GB, Potter SM (2015) Optogenetic feedback control of neural activity. eLife 4:e07192. doi:10.7554/eLife.07192
O’Connor DH, Hires SA, Guo ZV, Li N, Yu J, Sun Q-Q, Huber D, Svoboda K (2013) Neural coding during active somatosensation revealed using illusory touch. Nat Neurosci 16:958–965. doi:10.1038/nn.3419
Pouille F, Scanziani M (2001) Enforcement of temporal fidelity in pyramidal cells by somatic feed-forward inhibition. Science 293:1159–1163. doi:10.1126/science.1060342
Wehr M, Zador AM (2003) Balanced inhibition underlies tuning and sharpens spike timing in auditory cortex. Nature 426:442–446. doi:10.1038/nature02116
Allen BD, Singer AC, Boyden ES (2015) Principles of designing interpretable optogenetic behavior experiments. Learn Mem 22:232–238. doi:10.1101/lm.038026.114
Lee JH, Durand R, Gradinaru V, Zhang F, Goshen I, Kim D-S, Fenno LE, Ramakrishnan C, Deisseroth K (2010) Global and local fMRI signals driven by neurons defined optogenetically by type and wiring. Nature 465:788–792. doi:10.1038/nature09108
Schmid F, Wachsmuth L, Albers F, Schwalm M, Stroh A, Faber C (2017) True and apparent optogenetic BOLDfMRI signals. Magn Reson Med 77:126–136. doi:10.1002/mrm.26095
Berndt A, Yizhar O, Gunaydin LA, Hegemann P, Deisseroth K (2009) Bi-stable neural state switches. Nat Neurosci 12:229–234. doi:10.1038/nn.2247
Lu Y, Truccolo W, Wagner FBP, Vargas-Irwin CE, Ozden I, Zimmermann JB, May T, Agha N, Wang J, Nurmikko AV (2015) Optogenetically-induced spatiotemporal gamma oscillations and neuronal spiking activity in primate motor cortex. J Neurophysiol 113(10):3574–3587. doi:10.1152/jn.00792.2014
Wietek J, Beltramo R, Scanziani M, Hegemann P, Oertner TG, Simon Wiegert J (2015) An improved chloride-conducting channelrhodopsin for light-induced inhibition of neuronal activity in vivo. Sci Rep 5:14807. doi:10.1038/srep14807
Kim T, McCall JG, Jung YH, Huang X, Siuda ER, Li Y, Song J, Song YM, Pao HA, Kim R-H, Lu C, Lee SD, Song I-S, Shin G, Al-Hasani R, Kim S, Tan MP, Huang Y, Omenetto FG, Rogers JA, Bruchas MR (2013) Injectable, cellular-scale optoelectronics with applications for wireless optogenetics. Science 340:211–216. doi:10.1126/science.1232437
McCall JG, Kim T, Shin G, Huang X, Jung YH, Al-Hasani R, Omenetto FG, Bruchas MR, Rogers JA (2013) Fabrication and application of flexible, multimodal light-emitting devices for wireless optogenetics. Nat Protoc 8:2413–2428. doi:10.1038/nprot.2013.158
Park SI, Brenner DS, Shin G, Morgan CD, Copits BA, Chung HU, Pullen MY, Noh KN, Davidson S, Oh SJ, Yoon J, Jang K-I, Samineni VK, Norman M, Grajales-Reyes JG, Vogt SK, Sundaram SS, Wilson KM, Ha JS, Xu R, Pan T, Kim T, Huang Y, Montana MC, Golden JP, Bruchas MR, Gereau Iv RW, Rogers JA (2015) Soft, stretchable, fully implantable miniaturized optoelectronic systems for wireless optogenetics. Nat Biotechnol 33:1280–1286. doi:10.1038/nbt.3415
Pisanello F, Sileo L, Oldenburg IA, Pisanello M, Martiradonna L, Assad JA, Sabatini BL, De Vittorio M (2014) Multipoint-emitting optical fibers for spatially addressable in vivo optogenetics. Neuron 82:1245–1254. doi:10.1016/j.neuron.2014.04.041
Grossman N, Poher V, Grubb MS, Kennedy GT, Nikolic K, McGovern B, Palmini RB, Gong Z, Drakakis EM, Neil MAA, Dawson MD, Burrone J, Degenaar P (2010) Multi-site optical excitation using ChR2 and micro-LED array. J Neural Eng 7:016004. doi:10.1088/1741-2560/7/1/016004
Yizhar O, Fenno LE, Prigge M, Schneider F, Davidson TJ, O’Shea DJ, Sohal VS, Goshen I, Finkelstein J, Paz JT, Stehfest K, Fudim R, Ramakrishnan C, Huguenard JR, Hegemann P, Deisseroth K (2011) Neocortical excitation/inhibition balance in information processing and social dysfunction. Nature 477:171–178. doi:10.1038/nature10360
Breese GR, Knapp DJ, Criswell HE, Moy SS, Papadeas ST, Blake BL (2005) The neonate-6-hydroxydopamine-lesioned rat: a model for clinical neuroscience and neurobiological principles. Brain Res Rev 48:57–73. doi:10.1016/j.brainresrev.2004.08.004
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Karvat, G., Diester, I. (2018). Optophysiology and Behavior in Rodents and Nonhuman Primates. In: Stroh, A. (eds) Optogenetics: A Roadmap. Neuromethods, vol 133. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7417-7_11
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DOI: https://doi.org/10.1007/978-1-4939-7417-7_11
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