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

Yıl 2023, Cilt: 3 Sayı: 1, 64 - 87, 30.06.2023

Ceren Biçer , Ebrar Gültekin , Tayfun Sürmen , Burak Amil , Yasin Hasan Balcioglu

Öz

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.

Anahtar Kelimeler

Autism, clinical studies, depression, genetics, optogenetics, schizophrenia

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

Öz

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.

Anahtar Kelimeler

Depresyon, genetik, in vitro, klinik çalışma, optogenetik, otizm, şizofreni

Kaynakça

• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• Deisseroth, K. (2015). Optogenetics: 10 years of microbial opsins in neuroscience. Nature Neuroscience, 18(9), 1213–1225. https://doi.org/10.1038/nn.4091
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• Kehrer, C. (2008). Altered excitatory-inhibitory balance in the NMDA-hypofunction model of schizophrenia. Frontiers in Molecular Neuroscience, 1, 6.
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• Markram, K., & Markram, H. (2010). The intense world theory - A unifying theory of the neurobiology of autism. Frontiers in Human Neuroscience, 4, 224.
• Method of the Year 2010. (2011). Nature Methods, 8(1), 1. https://doi.org/10.1038/nmeth.f.321
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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.
• 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