Dergiler / Current Research and Reviews in Psychology and Psychiatry / 2026 / Cilt: 3 Sayı: 1

TRANSLASYONEL PERSPEKTİFTEN PSİKİYATRİK NÖROBİLİM VE OPTOGENETİK: RUHSAL BOZUKLUKLARDA TANILAMA VE TEDAVİ İÇİN ZORLUKLARI VE VADETTİKLERİ

PSYCHIATRIC NEUROSCIENCE AND OPTOGENETICS FROM A TRANSLATIONAL PERSPECTIVE: CHALLENGES AND PROMISES IN DIAGNOSIS AND TREATMENT OF MENTAL DISORDERS

Ceren Biçer(HACETTEPE ÜNİVERSİTESİ, TIP FAKÜLTESİ)0000-0002-1237-3723
Ebrar Gültekin(TOBB EKONOMİ VE TEKNOLOJİ ÜNİVERSİTESİ, TIP FAKÜLTESİ)0000-0001-8282-1360
Tayfun Sürmen(KARADENİZ TEKNİK ÜNİVERSİTESİ, TIP FAKÜLTESİ)0000-0001-5791-7010
Burak Amil(İSTANBUL MEDİPOL ÜNİVERSİTESİ, TIP FAKÜLTESİ)0000-0003-0918-3395
Yasin Hasan Balcioglu(SAĞLIK BİLİMLERİ ÜNİVERSİTESİ, İSTANBUL BAKIRKÖY PROF.DR. MAZHAR OSMAN RUH SAĞLIĞI VE SİNİR HASTALIKLARI SAĞLIK UYGULAMA VE ARAŞTIRMA MERKEZİ)0000-0002-1336-1724
Sayfa
64–87
Yayın Tarihi
2023-06-30
DOI
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⚡ TL;DR(1 Cümlede Hızlı Çıkarım)

Bu derleme yazısında optogenetiğin psikiyatrik nörobilim araştırmalarında, ruhsal bozuklukları tanılama ve tedavide güncel kullanımı kısa ve öz bir şekilde anlatılmaya çalışılmıştır.

📌 3 Maddede Bu Makale

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Amaç & Hipotez:Optogenetik, optik bilimi ve genetik mühendisliğin bir araya gelmesiyle elde edilen bir bilim dalıdır.
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Temel Bulgular & Veri:Dalga boyu ve ışık şiddetinin milisaniyelik değişimlerle ayarlanabilmesi ve bu sayede hücresel düzeyde spesifik gen ekspresyonunu ve protein trafiğini modüle edebilmesi sebebiyle optogenetik, diğer geleneksel laboratuvar yöntemlerinin başaramayacağı hücresel düzenlemelere imkan vermiştir. 2000’li yılların başında geliştirilen optogenetik yöntemler, moleküler ve hücresel olayların invivo ve invitro şekilde ışıkla manipüle edilerek araştırılmasına olanak sağlamıştır.
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Sonuç & Katkı:Bu derleme yazısında optogenetiğin psikiyatrik nörobilim araştırmalarında, ruhsal bozuklukları tanılama ve tedavide güncel kullanımı kısa ve öz bir şekilde anlatılmaya çalışılmıştır.
🔬Tür:Laboratuvar & Saha Deneyi
📍Kapsam:2000 Verileri
⚙️Değişkenler:Depresyon · genetik · in vitro

Özet

Optogenetik, optik bilimi ve genetik mühendisliğin bir araya gelmesiyle elde edilen bir bilim dalıdır. Dalga boyu ve ışık şiddetinin milisaniyelik değişimlerle ayarlanabilmesi ve bu sayede hücresel düzeyde spesifik gen ekspresyonunu ve protein trafiğini modüle edebilmesi sebebiyle optogenetik, diğer geleneksel laboratuvar yöntemlerinin başaramayacağı hücresel düzenlemelere imkan vermiştir. 2000’li yılların başında geliştirilen optogenetik yöntemler, moleküler ve hücresel olayların invivo ve invitro şekilde ışıkla manipüle edilerek araştırılmasına olanak sağlamıştır. Beyindeki spesifik nöronları ve nöral yolakları titizlikle stimüle ve inhibe edebilmesi sebebiyle bu yöntemler nörobilim araştırmalarında yaygın olarak kullanılmaktadır. Optogenetik yöntemler, davranış, nöral yolakların fizyolojisi ve patolojisi, kognisyon gibi pek çok alanı kavramamıza yardımcı olmuştur. Nörobilim alanında fizyoloji ve patolojiyi anlamak için yapılan çalışmalardaki katkılarıyla cevabı uzun zamandır muallak olan sorulara yanıt vermektedir. Karmaşık nöral fonksiyonların ve bozuklukların hücresel düzeyde anlaşılabilmesi, ruhsal ve nörodejeneratif bozukluklarda tanı ve tedavi yaklaşımları geliştirilmesini mümkün kılmaktadır. Bu derleme yazısında optogenetiğin psikiyatrik nörobilim araştırmalarında, ruhsal bozuklukları tanılama ve tedavide güncel kullanımı kısa ve öz bir şekilde anlatılmaya çalışılmıştır.

Abstract

Optogenetics, a method discovered in the early 2000s, has provided us the means to study molecular and cellular events by controlling them with light in both in vivo and in vitro conditions. Optogenetics is made up of the collaboration between optics and genetic engineering. Wavelength and light intensity can be changed by miliseconds, allowing researchers to modulate gene expression and protein trafficking. Hence, it provides us the opportunity to manipulate cellular events that can't be conducted through other conventional methods. The ability to selectively inhibit neurons and pathways in the brain has led to its widespread use in neuroscience. Optogenetics has helped us understand many concepts such as behavior, pathophysiology of neural pathways and cognition. Through its use in neuroscience, this method has shed light on unclear concepts both in physiology and neuropathology. Insight into the cellular mechanisms behind complex neural pathways and dysfunctions, will pave the way for new diagnostic and therapeutic modalities for psychiatric and neurodegenerative disorders. In this review, the role of optogenetics in psychiatric neuroscience studies and in the diagnosis and treatment of psychiatric disorders have been reviewed.

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Bu Makaleye Atıf Yap

Biçer, C., Gültekin, E., Sürmen, T., Amil, B., Balcioglu, Y. H. (2023). TRANSLASYONEL PERSPEKTİFTEN PSİKİYATRİK NÖROBİLİM VE OPTOGENETİK: RUHSAL BOZUKLUKLARDA TANILAMA VE TEDAVİ İÇİN ZORLUKLARI VE VADETTİKLERİ. Current Research and Reviews in Psychology and Psychiatry, Cilt: 3 Sayı: 1, 64–87. https://ajindex.com/articles/1611338

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Kaynakça (72)

  1. Adamantidis, A. R., Zhang, F., Aravanis, A. M., Deisseroth, K., & De Lecea, L. (2007). Neural substrates of awakening probed with optogenetic control of hypocretin neurons. Nature, 450(7168), 420–424. https://doi.org/10.1038/nature06310
  2. Adhikari, A., Lerner, T. N., Finkelstein, J., Pak, S., Jennings, J. H., Davidson, T. J., Ferenczi, E., Gunaydin, L. A., Mirzabekov, J. J., Ye, L., Kim, S. Y., Lei, A., & Deisseroth, K. (2015). Basomedial amygdala mediates top-down control of anxiety and fear. Nature, 527(7577), 179–185. https://doi.org/10.1038/nature15698
  3. Ahmari, S. E., Spellman, T., Douglass, N. L., Kheirbek, M. A., Simpson, H. B., Deisseroth, K., Gordon, J. A., & Hen, R. (2013). Repeated cortico-striatal stimulation generates persistent OCD-like behavior. Science, 340(6137), 1234–1239. https://doi.org/10.1126/science.1234733
  4. Allen, W. E., Chen, M. Z., Pichamoorthy, N., Tien, R. H., Pachitariu, M., Luo, L., & Deisseroth, K. (2019). Thirst regulates motivated behavior through modulation of brainwide neural population dynamics. Science, 364(6437). https://doi.org/10.1126/science.aav3932
  5. Autry, A. E., Wu, Z., Kapoor, V., Kohl, J., Bambah-Mukku, D., Rubinstein, N. D., Marin-Rodriguez, B., Carta, I., Sedwick, V., Tang, M., & Dulac, C. (2021). Urocortin-3 neurons in the mouse perifornical area promote infant-directed neglect and aggression. ELife, 10. https://doi.org/10.7554/eLife.64680
  6. Azim, E., Jiang, J., Alstermark, B., & Jessell, T. M. (2014). Skilled reaching relies on a V2a propriospinal internal copy circuit. Nature, 508(7496), 357–363. https://doi.org/10.1038/nature13021
  7. Bi, A., Cui, J., Ma, Y. P., Olshevskaya, E., Pu, M., Dizhoor, A. M., & Pan, Z. H. (2006). Ectopic Expression of a Microbial-Type Rhodopsin Restores Visual Responses in Mice with Photoreceptor Degeneration. Neuron, 50(1), 23–33. https://doi.org/10.1016/j.neuron.2006.02.026
  8. Boyden, E. S., Zhang, F., Bamberg, E., Nagel, G., & Deisseroth, K. (2005). Millisecond-timescale, genetically targeted optical control of neural activity. Nature Neuroscience, 8(9), 1263–1268. https://doi.org/10.1038/nn1525
  9. Brown, M. T. C., Tan, K. R., O’Connor, E. C., Nikonenko, I., Muller, D., & Lüscher, C. (2012). Ventral tegmental area GABA projections pause accumbal cholinergic interneurons to enhance associative learning. Nature, 492(7429), 452–456. https://doi.org/10.1038/nature11657
  10. Brumback, A. C., Ellwood, I. T., Kjaerby, C., Iafrati, J., Robinson, S., Lee, A. T., Patel, T., Nagaraj, S., Davatolhagh, F., & Sohal, V. S. (2018). Identifying specific prefrontal neurons that contribute to autism-associated abnormalities in physiology and social behavior. Molecular Psychiatry, 23(10), 2078–2089. https://doi.org/10.1038/mp.2017.213
  11. Cano, G., Mochizuki, T., & Saper, C. B. (2008). Neural circuitry of stress-induced insomnia in rats. Journal of Neuroscience, 28(40), 10167–10184. https://doi.org/10.1523/JNEUROSCI.1809-08.2008
  12. Cardin, J. A., Carlén, M., Meletis, K., Knoblich, U., Zhang, F., Deisseroth, K., Tsai, L. H., & Moore, C. I. (2009). Driving fast-spiking cells induces gamma rhythm and controls sensory responses. Nature, 459(7247), 663–667. https://doi.org/10.1038/nature08002
  13. Carta, I., Chen, C. H., Schott, A. L., Dorizan, S., & Khodakhah, K. (2019). Cerebellar modulation of the reward circuitry and social behavior. Science, 363(6424). https://doi.org/10.1126/science.aav0581
  14. Carter, M. E., Yizhar, O., Chikahisa, S., Nguyen, H., Adamantidis, A., Nishino, S., Deisseroth, K., & De Lecea, L. (2010). Tuning arousal with optogenetic modulation of locus coeruleus neurons. Nature Neuroscience, 13(12), 1526–1535. https://doi.org/10.1038/nn.2682
  15. Chemelli, R. M., Willie, J. T., Sinton, C. M., Elmquist, J. K., Scammell, T., Lee, C., Richardson, J. A., Clay Williams, S., Xiong, Y., Kisanuki, Y., Fitch, T. E., Nakazato, M., Hammer, R. E., Saper, C. B., & Yanagisawa, M. (1999). Narcolepsy in orexin knockout mice: Molecular genetics of sleep regulation. Cell, 98(4), 437–451. https://doi.org/10.1016/S0092-8674(00)81973-X
  16. Choi, G. B., Stettler, D. D., Kallman, B. R., Bhaskar, S. T., Fleischmann, A., & Axel, R. (2011). Driving opposing behaviors with ensembles of piriform neurons. Cell, 146(6), 1004–1015. https://doi.org/10.1016/j.cell.2011.07.041
  17. Cohen, J. Y., Haesler, S., Vong, L., Lowell, B. B., & Uchida, N. (2012). Neuron-type-specific signals for reward and punishment in the ventral tegmental area. Nature, 482(7383), 85–88. https://doi.org/10.1038/nature10754
  18. Creed, M., Pascoli, V. J., & Lüscher, C. (2015). Refining Deep brain stimulation to emulate optogenetic treatment of synaptic pathology. Science, 347(6222), 659–664. https://doi.org/10.1126/science.1260776
  19. Deisseroth, K. (2012). Optogenetics and psychiatry: Applications, challenges, and opportunities. Biological Psychiatry, 71(12), 1030–1032. https://doi.org/10.1016/j.biopsych.2011.12.021
  20. Deisseroth, K. (2015). Optogenetics: 10 years of microbial opsins in neuroscience. Nature Neuroscience, 18(9), 1213–1225. https://doi.org/10.1038/nn.4091
  21. Domingos, A. I., Vaynshteyn, J., Voss, H. U., Ren, X., Gradinaru, V., Zang, F., Deisseroth, K., De Araujo, I. E., & Friedman, J. (2011). Leptin regulates the reward value of nutrient. Nature Neuroscience, 14(12), 1562–1568. https://doi.org/10.1038/nn.2977
  22. Fakhoury, M. (2021). Optogenetics: A revolutionary approach for the study of depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 106, 110094. https://doi.org/10.1016/j.pnpbp.2020.110094
  23. Francis, T. C., Chandra, R., Friend, D. M., Finkel, E., Dayrit, G., Miranda, J., Brooks, J. M., Iñiguez, S. D., O’Donnell, P., Kravitz, A., & Lobo, M. K. (2015). Nucleus accumbens medium spiny neuron subtypes mediate depression-related outcomes to social defeat stress. Biological Psychiatry, 77(3), 212–222. https://doi.org/10.1016/j.biopsych.2014.07.021
  24. Garg, S. J., & Federman, J. (2013). Optogenetics, visual prosthesis and electrostimulation for retinal dystrophies. Current Opinion in Ophthalmology, 24(5), 407–414. https://doi.org/10.1097/ICU.0b013e328363829b
  25. Goshen, I., Brodsky, M., Prakash, R., Wallace, J., Gradinaru, V., Ramakrishnan, C., & Deisseroth, K. (2011). Dynamics of Retrieval Strategies for Remote Memories. Cell, 147(3), 678–689. https://doi.org/10.1016/j.cell.2011.11.006
  26. Hägglund, M., Borgius, L., Dougherty, K. J., & Kiehn, O. (2010). Activation of groups of excitatory neurons in the mammalian spinal cord or hindbrain evokes locomotion. Nature Neuroscience, 13(2), 246–252. https://doi.org/10.1038/nn.2482
  27. Hare, B. D., Shinohara, R., Liu, R. J., Pothula, S., DiLeone, R. J., & Duman, R. S. (2019). Optogenetic stimulation of medial prefrontal cortex Drd1 neurons produces rapid and long-lasting antidepressant effects. Nature Communications, 10(1), 1–12. https://doi.org/10.1038/s41467-018-08168-9
  28. Hunnicutt, B. J., Long, B. R., Kusefoglu, D., Gertz, K. J., Zhong, H., & Mao, T. (2014). A comprehensive thalamocortical projection map at the mesoscopic level. Nature Neuroscience, 17(9), 1276–1285. https://doi.org/10.1038/nn.3780
  29. Islam, M. T., Maejima, T., Matsui, A., & Mieda, M. (2022). Paraventricular hypothalamic vasopressin neurons induce self-grooming in mice. Molecular Brain, 15(1), 1–14. https://doi.org/10.1186/s13041-022-00932-9
  30. James, S. L., Abate, D., Abate, K. H., Abay, S. M., Abbafati, C., Abbasi, N., et al. (2018). Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. The Lancet, 392(10159), 1789–1858. https://doi.org/10.1016/S0140-6736(18)32279-7
  31. Jego, S., Glasgow, S. D., Herrera, C. G., Ekstrand, M., Reed, S. J., Boyce, R., Friedman, J., Burdakov, D., & Adamantidis, A. R. (2013). Optogenetic identification of a rapid eye movement sleep modulatory circuit in the hypothalamus. Nature Neuroscience, 16(11), 1637–1643. https://doi.org/10.1038/nn.3522
  32. Jennings, J. H., Kim, C. K., Marshel, J. H., Raffiee, M., Ye, L., Quirin, S., Pak, S., Ramakrishnan, C., & Deisseroth, K. (2019). Interacting neural ensembles in orbitofrontal cortex for social and feeding behaviour. Nature, 565(7741), 645–649. https://doi.org/10.1038/s41586-018-0866-8
  33. Jennings, J. H., Ung, R. L., Resendez, S. L., Stamatakis, A. M., Taylor, J. G., Huang, J., Veleta, K., Kantak, P. A., Aita, M., Shilling-Scrivo, K., Ramakrishnan, C., Deisseroth, K., Otte, S., & Stuber, G. D. (2015). Visualizing hypothalamic network dynamics for appetitive and consummatory behaviors. Cell, 160(3), 516–527. https://doi.org/10.1016/j.cell.2014.12.026
  34. Jimenez, J. C., Su, K., Goldberg, A. R., Luna, V. M., Biane, J. S., Ordek, G., Zhou, P., Ong, S. K., Wright, M. A., Zweifel, L., Paninski, L., Hen, R., & Kheirbek, M. A. (2018). Anxiety Cells in a Hippocampal-Hypothalamic Circuit. Neuron, 97(3), 670-683.e6. https://doi.org/10.1016/j.neuron.2018.01.016
  35. Johansen, J. P., Hamanaka, H., Monfils, M. H., Behnia, R., Deisseroth, K., Blair, H. T., & LeDoux, J. E. (2010). Optical activation of lateral amygdala pyramidal cells instructs associative fear learning. Proceedings of the National Academy of Sciences of the United States of America, 107(28), 12692–12697. https://doi.org/10.1073/pnas.1002418107
  36. Jones, J. R., Tackenberg, M. C., & Mcmahon, D. G. (2015). Manipulating circadian clock neuron firing rate resets molecular circadian rhythms and behavior. Nature Neuroscience, 18(3), 373–377. https://doi.org/10.1038/nn.3937
  37. Kehrer, C. (2008). Altered excitatory-inhibitory balance in the NMDA-hypofunction model of schizophrenia. Frontiers in Molecular Neuroscience, 1, 6.
  38. Kim, T., Thankachan, S., McKenna, J. T., McNally, J. M., Yang, C., Choi, J. H., Chen, L., Kocsis, B., Deisseroth, K., Strecker, R. E., Basheer, R., Brown, R. E., & McCarley, R. W. (2015). Cortically projecting basal forebrain parvalbumin neurons regulate cortical gamma band oscillations. Proceedings of the National Academy of Sciences of the United States of America, 112(11), 3535–3540. https://doi.org/10.1073/PNAS.1413625112
  39. Knowland, D., Lilascharoen, V., Pacia, C. P., Shin, S., Wang, E. H. J., & Lim, B. K. (2017). Distinct Ventral Pallidal Neural Populations Mediate Separate Symptoms of Depression. Cell, 170(2), 284-297.e18. https://doi.org/10.1016/j.cell.2017.06.015
  40. Kravitz, A. V., Freeze, B. S., Parker, P. R. L., Kay, K., Thwin, M. T., Deisseroth, K., & Kreitzer, A. C. (2010). Regulation of parkinsonian motor behaviours by optogenetic control of basal ganglia circuitry. Nature, 466(7306), 622–626. https://doi.org/10.1038/nature09159
  41. Kress, G. J., Yamawaki, N., Wokosin, D. L., Wickersham, I. R., Shepherd, G. M. G., & Surmeier, D. J. (2013). Convergent cortical innervation of striatal projection neurons. Nature Neuroscience, 16(6), 665–667. https://doi.org/10.1038/nn.3397
  42. Krook-Magnuson, E., Armstrong, C., Oijala, M., & Soltesz, I. (2013). On-demand optogenetic control of spontaneous seizures in temporal lobe epilepsy. Nature Communications, 4(1), 1–8. https://doi.org/10.1038/ncomms2376
  43. Lee, H., Kim, D. W., Remedios, R., Anthony, T. E., Chang, A., Madisen, L., Zeng, H., & Anderson, D. J. (2014). Scalable control of mounting and attack by Esr1+ neurons in the ventromedial hypothalamus. Nature, 509(7502), 627–632. https://doi.org/10.1038/nature13169
  44. Lee, S. H., Kwan, A. C., Zhang, S., Phoumthipphavong, V., Flannery, J. G., Masmanidis, S. C., Taniguchi, H., Huang, Z. J., Zhang, F., Boyden, E. S., Deisseroth, K., & Dan, Y. (2012). Activation of specific interneurons improves V1 feature selectivity and visual perception. Nature, 488(7411), 379–383. https://doi.org/10.1038/nature11312
  45. Lewis, D. A., Curley, A. A., Glausier, J. R., & Volk, D. W. (2012). Cortical parvalbumin interneurons and cognitive dysfunction in schizophrenia. Trends in Neurosciences, 35(1), 57–67. https://doi.org/10.1016/j.tins.2011.10.004
  46. Lin, D., Boyle, M. P., Dollar, P., Lee, H., Lein, E. S., Perona, P., & Anderson, D. J. (2011). Functional identification of an aggression locus in the mouse hypothalamus. Nature, 470(7333), 221–227. https://doi.org/10.1038/nature09736
  47. Liu, B., Cao, Y., Wang, J., & Dong, J. (2020). Excitatory transmission from ventral pallidum to lateral habenula mediates depression. World Journal of Biological Psychiatry, 21(8), 627–633. https://doi.org/10.1080/15622975.2020.1725117
  48. Lu, J., Zhang, Z., Yin, X., Tang, Y., Ji, R., Chen, H., Guang, Y., Gong, X., He, Y., Zhou, W., Wang, H., Cheng, K., Wang, Y., Chen, X., Xie, P., & Guo, Z. V. (2022). An entorhinal-visual cortical circuit regulates depression-like behaviors. Molecular Psychiatry. https://doi.org/10.1038/s41380-022-01540-8
  49. Markram, K., & Markram, H. (2010). The intense world theory - A unifying theory of the neurobiology of autism. Frontiers in Human Neuroscience, 4, 224.
  50. Method of the Year 2010. (2011). Nature Methods, 8(1), 1. https://doi.org/10.1038/nmeth.f.321
  51. Ohmura, Y., Tsutsui-Kimura, I., Sasamori, H., Nebuka, M., Nishitani, N., Tanaka, K. F., Yamanaka, A., & Yoshioka, M. (2020). Different roles of distinct serotonergic pathways in anxiety-like behavior, antidepressant-like, and anti-impulsive effects. Neuropharmacology, 167, 107703. https://doi.org/10.1016/j.neuropharm.2019.107703
  52. Oka, Y., Ye, M., & Zuker, C. S. (2015). Thirst driving and suppressing signals encoded by distinct neural populations in the brain. Nature, 520(7547), 349–352. https://doi.org/10.1038/nature14108
  53. Peyron, C., Faraco, J., Rogers, W., Ripley, B., Overeem, S., Charnay, Y., Nevsimalova, S., Aldrich, M., Reynolds, D., Albin, R., Li, R., Hungs, M., Pedrazzoli, M., Padigaru, M., Kucherlapati, M., Jun, F., Maki, R., Lammers, G. J., Bouras, C., … Mignot, E. (2000). A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains. Nature Medicine, 6(9), 991–997. https://doi.org/10.1038/79690
  54. Prakash, J., Das, R., Srivastava, K., Bhat, P., Shashikumar, R., & Gupta, A. (2012). Optogenetics in psychiatry: The light ahead. Industrial Psychiatry Journal, 21(2), 160. https://doi.org/10.4103/0972-6748.119650
  55. Ramirez, S., Liu, X., MacDonald, C. J., Moffa, A., Zhou, J., Redondo, R. L., & Tonegawa, S. (2015). Activating positive memory engrams suppresses depression-like behaviour. Nature, 522(7556), 335–339. https://doi.org/10.1038/nature14514
  56. Rich, M. T., Huang, Y. H., & Torregrossa, M. M. (2021). Using optogenetics to reverse neuroplasticity and inhibit cocaine seeking in rats. Journal of Visualized Experiments, 176. https://doi.org/10.3791/63185
  57. Shirai, F., & Hayashi-Takagi, A. (2017). Optogenetics: Applications in psychiatric research. Psychiatry and Clinical Neurosciences, 71(6), 363–372. https://doi.org/10.1111/pcn.12516
  58. Sohal, V. S., Zhang, F., Yizhar, O., & Deisseroth, K. (2009). Parvalbumin neurons and gamma rhythms enhance cortical circuit performance. Nature, 459(7247), 698–702. https://doi.org/10.1038/nature07991
  59. Thannickal, T. C., Moore, R. Y., Nienhuis, R., Ramanathan, L., Gulyani, S., Aldrich, M., Cornford, M., & Siegel, J. M. (2000). Reduced number of hypocretin neurons in human narcolepsy. Neuron, 27(3), 469–474. https://doi.org/10.1016/S0896-6273(00)00058-1
  60. Thanos, P. K., Robison, L., Nestler, E. J., Kim, R., Michaelides, M., Lobo, M. K., & Volkow, N. D. (2013). Mapping brain metabolic connectivity in awake rats with μPET and optogenetic stimulation. Journal of Neuroscience, 33(15), 6343–6349. https://doi.org/10.1523/JNEUROSCI.4997-12.2013
  61. Ting, J. T., & Feng, G. (2011). Neurobiology of obsessive-compulsive disorder: Insights into neural circuitry dysfunction through mouse genetics. Current Opinion in Neurobiology, 21(6), 842–848. https://doi.org/10.1016/j.conb.2011.04.010
  62. Tye, K. M., Mirzabekov, J. J., Warden, M. R., Ferenczi, E. A., Tsai, H. C., Finkelstein, J., Kim, S. Y., Adhikari, A., Thompson, K. R., Andalman, A. S., Gunaydin, L. A., Witten, I. B., & Deisseroth, K. (2013). Dopamine neurons modulate neural encoding and expression of depression-related behaviour. Nature, 493(7433), 537–541. https://doi.org/10.1038/nature11740
  63. Vesuna, S., Kauvar, I. V., Richman, E., Gore, F., Oskotsky, T., Sava-Segal, C., Luo, L., Malenka, R. C., Henderson, J. M., Nuyujukian, P., Parvizi, J., & Deisseroth, K. (2020). Deep posteromedial cortical rhythm in dissociation. Nature, 586(7827), 87–94. https://doi.org/10.1038/s41586-020-2731-9
  64. Vetere, G., Tran, L. M., Moberg, S., Steadman, P. E., Restivo, L., Morrison, F. G., Ressler, K. J., Josselyn, S. A., & Frankland, P. W. (2019). Memory formation in the absence of experience. Nature Neuroscience, 22(6), 933–940. https://doi.org/10.1038/s41593-019-0389-0
  65. Walsh, J. J., Christoffel, D. J., Heifets, B. D., Ben-Dor, G. A., Selimbeyoglu, A., Hung, L. W., Deisseroth, K., & Malenka, R. C. (2018). 5-HT release in nucleus accumbens rescues social deficits in mouse autism model. Nature, 560(7720), 589–594. https://doi.org/10.1038/s41586-018-0416-4
  66. Wang, L., Chen, I. Z., & Lin, D. (2015). Collateral Pathways from the Ventromedial Hypothalamus Mediate Defensive Behaviors. Neuron, 85(6), 1344–1358. https://doi.org/10.1016/j.neuron.2014.12.025
  67. Willsey, A. J., Sanders, S. J., Li, M., Dong, S., Tebbenkamp, A. T., Muhle, R. A., Reilly, S. K., Lin, L., Fertuzinhos, S., Miller, J. A., Murtha, M. T., Bichsel, C., Niu, W., Cotney, J., Ercan-Sencicek, A. G., Gockley, J., Gupta, A. R., Han, W., He, X., … State, M. W. (2013). Coexpression networks implicate human midfetal deep cortical projection neurons in the pathogenesis of autism. Cell, 155(5), 997. https://doi.org/10.1016/j.cell.2013.10.020
  68. Witten, I. B., Lin, S. C., Brodsky, M., Prakash, R., Diester, I., Anikeeva, P., Gradinaru, V., Ramakrishnan, C., & Deisseroth, K. (2010). Cholinergic interneurons control local circuit activity and cocaine conditioning. Science, 330(6011), 1677–1681. https://doi.org/10.1126/science.1193771
  69. Wu, Z., Autry, A. E., Bergan, J. F., Watabe-Uchida, M., & Dulac, C. G. (2014). Galanin neurons in the medial preoptic area govern parental behaviour. Nature, 509(7500), 325–330. https://doi.org/10.1038/nature13307
  70. Yizhar, O., Fenno, L. E., Prigge, M., Schneider, F., Davidson, T. J., Ogshea, D. J., Sohal, V. S., Goshen, I., Finkelstein, J., Paz, J. T., Stehfest, K., Fudim, R., Ramakrishnan, C., Huguenard, J. R., Hegemann, P., & Deisseroth, K. (2011). Neocortical excitation/inhibition balance in information processing and social dysfunction. Nature, 477(7363), 171–178. https://doi.org/10.1038/nature10360
  71. Zhang, H., Chaudhury, D., Nectow, A., … A. F.-B., & 2019, U. (2019). α1-and β3-adrenergic receptor–mediated mesolimbic homeostatic plasticity confers resilience to social stress in susceptible mice. Biological Psychiatry, 85(3), 226–236.
  72. Zhang, X. Y., Peng, S. Y., Shen, L. P., Zhuang, Q. X., Li, B., Xie, S. T., Li, Q. X., Shi, M. R., Ma, T. Y., Zhang, Q., Wang, J. J., & Zhu, J. N. (2020). Targeting presynaptic H3 heteroreceptor in nucleus accumbens to improve anxiety and obsessive-compulsive-like behaviors. Proceedings of the National Academy of Sciences of the United States of America, 117(50), 32155–32164. https://doi.org/10.1073/pnas.2008456117