Hitoshi Morikawa

Associate Professor
M. June and J. Virgil Waggoner Professorships in Molecular Biology

Neuroscience
Interdisciplinary Life Sciences Graduate Programs

morikawa@austin.utexas.edu

Biography

After obtaining an M.D. from Kyoto University in Japan in 1990 and completing his clinical training in anesthesiology, Dr. Morikawa became interested in basic research. After obtaining a Ph.D in the field of anesthesiology & neuropharmacology in 1999, Dr. Morikawa joined John Williams’ lab at the Vollum Institute in Portland, Oregon, with a naive intention to define the brain circuit involved in the euphoric action of drugs of abuse. He moved to UT Austin as a faculty in 2002 after 3 years of postdoctoral training. His current interest focuses on the reward learning mechanisms driving the development of addicitive behaviors.

Research

The primary focus of Morikawa lab is to investigate neural plasticity in the mesostriatal dopaminergic system underlying reward-based learning and the development of addiction. We are particularly interested in the cellular mechanisms driving calcium-dependent regulation of neuronal activity and plasticity. Using brain slice electrophysiology, calcium imaging, and UV photolysis of caged compounds, my lab has been conducting studies investigating the role of calcium signaling in regulating physiology and plasticity of neurons in the mesostriatal dopaminergic system. We have also implemented behavioral assays (e.g., conditioned place preference, food conditioned approach, etc.) combined with stereotaxic injection of pharmacological agents and viruses to manipulate specific brain areas. In this way, we aim to link specific signaling processes at the cellular and molecular level to learning processes and addictive behavior in behaving animals. Our latest interest is on the impact of daily life experience (stress, diet, exercise, etc.) on these processes to determine the risk factors and therapeutic strategies for neuropyschiatric conditions arising from dysregulation of the dopaminergic system, such as addiction, schizophrenia, and depression.

Research Areas

Neuroscience
Health Promotion or Disease Prevention
Substance Use Disorders

Fields of Interest

Electrophys, Optogenetics & Chemogenetics
Behavior
Cellular/Molecular/Structure
Neurological Disease/Addiction

Publications

Natal S, Young CC, Kaur K, Gebhardt ES, Perrone A, Morikawa H, Tirado C, Smits JAJ. Applications of isradipine in human addiction studies: A systematic literature review. Exp Clin Psychopharmacol. 2023 Apr;31(2):507-522. doi: 10.1037/pha0000633. Epub 2023 Jan 2. PubMed PMID: 36595455.
Morikawa H, Young CC, Smits JA. Usage of L-type calcium channel blockers to suppress drug reward and memory driving addiction: Past, present, and future. Neuropharmacology. 2022 Dec 15;221:109290. doi: 10.1016/j.neuropharm.2022.109290. Epub 2022 Oct 12. Review. PubMed PMID: 36241085.
Papini S, Young CC, Gebhardt CS, Perrone A, Morikawa H, Otto MW, Roache JD, Smits JAJ. Isradipine enhancement of virtual reality cue exposure for smoking cessation: Rationale and study protocol for a double-blind randomized controlled trial. Contemp Clin Trials. 2020 Jul;94:106013. doi: 10.1016/j.cct.2020.106013. Epub 2020 Apr 24. PubMed PMID: 32335287; PubMed Central PMCID: PMC7446235.
Dobbs LK, Morikawa H. Biasing Neurotensin Receptor Signaling to Arrest Psychostimulant Abuse. Cell. 2020 Jun 11;181(6):1205-1206. doi: 10.1016/j.cell.2020.05.009. Epub 2020 May 28. PubMed PMID: 32470394.
Pomrenze MB, Tovar-Diaz J, Blasio A, Maiya R, Giovanetti SM, Lei K, Morikawa H, Hopf FW, Messing RO. A Corticotropin Releasing Factor Network in the Extended Amygdala for Anxiety. J Neurosci. 2019 Feb 6;39(6):1030-1043. doi: 10.1523/JNEUROSCI.2143-18.2018. Epub 2018 Dec 10. PubMed PMID: 30530860; PubMed Central PMCID: PMC6363927.
Tovar-Díaz J, Pomrenze MB, Kan R, Pahlavan B, Morikawa H. Cooperative CRF and α1 Adrenergic Signaling in the VTA Promotes NMDA Plasticity and Drives Social Stress Enhancement of Cocaine Conditioning. Cell Rep. 2018 Mar 6;22(10):2756-2766. doi: 10.1016/j.celrep.2018.02.039. PubMed PMID: 29514102; PubMed Central PMCID: PMC5877815.
Gantz SC, Ford CP, Morikawa H, Williams JT. The Evolving Understanding of Dopamine Neurons in the Substantia Nigra and Ventral Tegmental Area. Annu Rev Physiol. 2018 Feb 10;80:219-241. doi: 10.1146/annurev-physiol-021317-121615. Epub 2017 Sep 22. Review. PubMed PMID: 28938084.
Cook JB, Hendrickson LM, Garwood GM, Toungate KM, Nania CV, Morikawa H. Junk food diet-induced obesity increases D2 receptor autoinhibition in the ventral tegmental area and reduces ethanol drinking. PLoS One. 2017;12(8):e0183685. doi: 10.1371/journal.pone.0183685. eCollection 2017. PubMed PMID: 28859110; PubMed Central PMCID: PMC5578487.
Stelly CE, Pomrenze MB, Cook JB, Morikawa H. Repeated social defeat stress enhances glutamatergic synaptic plasticity in the VTA and cocaine place conditioning. Elife. 2016 Jul 4;5. doi: 10.7554/eLife.15448. PubMed PMID: 27374604; PubMed Central PMCID: PMC4931908.

Swapna I, Bondy B, Morikawa H. Differential Dopamine Regulation of Ca(2+) Signaling and Its Timing Dependence in the Nucleus Accumbens. Cell Rep. 2016 Apr 19;15(3):563-573. doi: 10.1016/j.celrep.2016.03.055. Epub 2016 Apr 7. PubMed PMID: 27068462; PubMed Central PMCID: PMC4838497.
Degoulet M, Stelly CE, Ahn KC, Morikawa H. L-type Ca²⁺ channel blockade with antihypertensive medication disrupts VTA synaptic plasticity and drug-associated contextual memory. Mol Psychiatry. 2016 Mar;21(3):394-402. doi: 10.1038/mp.2015.84. Epub 2015 Jun 23. PubMed PMID: 26100537; PubMed Central PMCID: PMC4689680.
Whitaker LR, Hendrickson LM, Morikawa H. Neural Plasticity in the Ventral Tegmental Area and Alcohol Addiction. In: Noronha AB, Cui C, Harris RA, Crabbe JC, editors. Neurobiology of Alcohol Dependence Academic Press: Elsevier; 2014. Chapter 12; p.227-249.
Cui C, Noronha A, Morikawa H, Alvarez VA, Stuber GD, Szumlinski KK, Kash TL, Roberto M, Wilcox MV. New insights on neurobiological mechanisms underlying alcohol addiction. Neuropharmacology. 2013 Apr;67:223-32. doi: 10.1016/j.neuropharm.2012.09.022. Epub 2012 Nov 13. Review. PubMed PMID: 23159531; PubMed Central PMCID: PMC3562413.
Clements MA, Swapna I, Morikawa H. Inositol 1,4,5-triphosphate drives glutamatergic and cholinergic inhibition selectively in spiny projection neurons in the striatum. J Neurosci. 2013 Feb 6;33(6):2697-708. doi: 10.1523/JNEUROSCI.4759-12.2013. PubMed PMID: 23392696; PubMed Central PMCID: PMC3572919.
Whitaker LR, Degoulet M, Morikawa H. Social deprivation enhances VTA synaptic plasticity and drug-induced contextual learning. Neuron. 2013 Jan 23;77(2):335-45. doi: 10.1016/j.neuron.2012.11.022. PubMed PMID: 23352169; PubMed Central PMCID: PMC3559005.
Beatty JA, Sullivan MA, Morikawa H, Wilson CJ. Complex autonomous firing patterns of striatal low-threshold spike interneurons. J Neurophysiol. 2012 Aug 1;108(3):771-81. doi: 10.1152/jn.00283.2012. Epub 2012 May 9. PubMed PMID: 22572945; PubMed Central PMCID: PMC3424086.
Morikawa H, Paladini CA. Dynamic regulation of midbrain dopamine neuron activity: intrinsic, synaptic, and plasticity mechanisms. Neuroscience. 2011 Dec 15;198:95-111. doi: 10.1016/j.neuroscience.2011.08.023. Epub 2011 Aug 16. Review. PubMed PMID: 21872647; PubMed Central PMCID: PMC3221882.
Blednov YA, Benavidez JM, Geil C, Perra S, Morikawa H, Harris RA. Activation of inflammatory signaling by lipopolysaccharide produces a prolonged increase of voluntary alcohol intake in mice. Brain Behav Immun. 2011 Jun;25 Suppl 1:S92-S105. doi: 10.1016/j.bbi.2011.01.008. Epub 2011 Jan 23. PubMed PMID: 21266194; PubMed Central PMCID: PMC3098320.
Bernier BE, Whitaker LR, Morikawa H. Previous ethanol experience enhances synaptic plasticity of NMDA receptors in the ventral tegmental area. J Neurosci. 2011 Apr 6;31(14):5205-12. doi: 10.1523/JNEUROSCI.5282-10.2011. PubMed PMID: 21471355; PubMed Central PMCID: PMC3086894.
Morikawa H, Harris RA. Small K channels: big targets for treating alcoholism?. Biol Psychiatry. 2011 Apr 1;69(7):614-5. doi: 10.1016/j.biopsych.2011.01.016. PubMed PMID: 21397742; PubMed Central PMCID: PMC3108455.
Perra S, Clements MA, Bernier BE, Morikawa H. In vivo ethanol experience increases D(2) autoinhibition in the ventral tegmental area. Neuropsychopharmacology. 2011 Apr;36(5):993-1002. doi: 10.1038/npp.2010.237. Epub 2011 Jan 19. PubMed PMID: 21248720; PubMed Central PMCID: PMC3077268.
Theile JW, Morikawa H, Gonzales RA, Morrisett RA. GABAergic transmission modulates ethanol excitation of ventral tegmental area dopamine neurons. Neuroscience. 2011 Jan 13;172:94-103. doi: 10.1016/j.neuroscience.2010.10.046. Epub 2010 Oct 23. PubMed PMID: 20974231; PubMed Central PMCID: PMC3010434.
Ahn KC, Bernier BE, Harnett MT, Morikawa H. IP3 receptor sensitization during in vivo amphetamine experience enhances NMDA receptor plasticity in dopamine neurons of the ventral tegmental area. J Neurosci. 2010 May 12;30(19):6689-99. doi: 10.1523/JNEUROSCI.4453-09.2010. PubMed PMID: 20463231; PubMed Central PMCID: PMC2881312.
Morikawa H, Morrisett RA. Ethanol action on dopaminergic neurons in the ventral tegmental area: interaction with intrinsic ion channels and neurotransmitter inputs. Int Rev Neurobiol. 2010;91:235-88. doi: 10.1016/S0074-7742(10)91008-8. Review. PubMed PMID: 20813245; PubMed Central PMCID: PMC2936723.
Harnett MT, Bernier BE, Ahn KC, Morikawa H. Burst-timing-dependent plasticity of NMDA receptor-mediated transmission in midbrain dopamine neurons. Neuron. 2009 Jun 25;62(6):826-38. doi: 10.1016/j.neuron.2009.05.011. PubMed PMID: 19555651; PubMed Central PMCID: PMC2702773.
Theile JW, Morikawa H, Gonzales RA, Morrisett RA. Role of 5-hydroxytryptamine2C receptors in Ca2+-dependent ethanol potentiation of GABA release onto ventral tegmental area dopamine neurons. J Pharmacol Exp Ther. 2009 May;329(2):625-33. doi: 10.1124/jpet.108.147793. Epub 2009 Feb 18. PubMed PMID: 19225162; PubMed Central PMCID: PMC2672866.
Sullivan MA, Chen H, Morikawa H. Recurrent inhibitory network among striatal cholinergic interneurons. J Neurosci. 2008 Aug 27;28(35):8682-90. doi: 10.1523/JNEUROSCI.2411-08.2008. PubMed PMID: 18753369; PubMed Central PMCID: PMC2561080.
Theile JW, Morikawa H, Gonzales RA, Morrisett RA. Ethanol enhances GABAergic transmission onto dopamine neurons in the ventral tegmental area of the rat. Alcohol Clin Exp Res. 2008 Jun;32(6):1040-8. doi: 10.1111/j.1530-0277.2008.00665.x. Epub 2008 Apr 15. PubMed PMID: 18422836; PubMed Central PMCID: PMC2553853.
Cui G, Bernier BE, Harnett MT, Morikawa H. Differential regulation of action potential- and metabotropic glutamate receptor-induced Ca2+ signals by inositol 1,4,5-trisphosphate in dopaminergic neurons. J Neurosci. 2007 Apr 25;27(17):4776-85. doi: 10.1523/JNEUROSCI.0139-07.2007. PubMed PMID: 17460090; PubMed Central PMCID: PMC1941773.
Ponomarev I, Maiya R, Harnett MT, Schafer GL, Ryabinin AE, Blednov YA, Morikawa H, Boehm SL 2nd, Homanics GE, Berman AE, Lodowski KH, Bergeson SE, Harris RA. Transcriptional signatures of cellular plasticity in mice lacking the alpha1 subunit of GABAA receptors. J Neurosci. 2006 May 24;26(21):5673-83. doi: 10.1523/JNEUROSCI.0860-06.2006. PubMed PMID: 16723524; PubMed Central PMCID: PMC1894896.
Okamoto T, Harnett MT, Morikawa H. Hyperpolarization-activated cation current (Ih) is an ethanol target in midbrain dopamine neurons of mice. J Neurophysiol. 2006 Feb;95(2):619-26. doi: 10.1152/jn.00682.2005. Epub 2005 Sep 7. PubMed PMID: 16148268; PubMed Central PMCID: PMC1454360.
Cui G, Okamoto T, Morikawa H. Spontaneous opening of T-type Ca2+ channels contributes to the irregular firing of dopamine neurons in neonatal rats. J Neurosci. 2004 Dec 8;24(49):11079-87. doi: 10.1523/JNEUROSCI.2713-04.2004. PubMed PMID: 15590924; PubMed Central PMCID: PMC1454359.
Morikawa H. [My research activity in the Waggoner Center for Alcohol and Addiction Research]. Nihon Seirigaku Zasshi. 2004;66(6):202-3. PubMed PMID: 15291259.
Paladini CA, Robinson S, Morikawa H, Williams JT, Palmiter RD. Dopamine controls the firing pattern of dopamine neurons via a network feedback mechanism. Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2866-71. doi: 10.1073/pnas.0138018100. Epub 2003 Feb 25. PubMed PMID: 12604788; PubMed Central PMCID: PMC151432.
Morikawa H, Khodakhah K, Williams JT. Two intracellular pathways mediate metabotropic glutamate receptor-induced Ca2+ mobilization in dopamine neurons. J Neurosci. 2003 Jan 1;23(1):149-57. PubMed PMID: 12514211; PubMed Central PMCID: PMC1408315.
Shoda T, Fukuda K, Uga H, Mima H, Morikawa H. Activation of mu-opioid receptor induces expression of c-fos and junB via mitogen-activated protein kinase cascade. Anesthesiology. 2001 Oct;95(4):983-9. doi: 10.1097/00000542-200110000-00030. PubMed PMID: 11605942.
Paladini CA, Fiorillo CD, Morikawa H, Williams JT. Amphetamine selectively blocks inhibitory glutamate transmission in dopamine neurons. Nat Neurosci. 2001 Mar;4(3):275-81. doi: 10.1038/85124. PubMed PMID: 11224544.
Morikawa H, Manzoni OJ, Crabbe JC, Williams JT. Regulation of central synaptic transmission by 5-HT(1B) auto- and heteroreceptors. Mol Pharmacol. 2000 Dec;58(6):1271-8. doi: 10.1124/mol.58.6.1271. PubMed PMID: 11093763.
Morikawa H, Imani F, Khodakhah K, Williams JT. Inositol 1,4,5-triphosphate-evoked responses in midbrain dopamine neurons. J Neurosci. 2000 Oct 15;20(20):RC103. PubMed PMID: 11027254; PubMed Central PMCID: PMC6772861.
Morikawa H, Mima H, Uga H, Shoda T, Fukuda K. Opioid potentiation of N-type Ca2+ channel currents via pertussis-toxin-sensitive G proteins in NG108-15 cells. Pflugers Arch. 1999 Aug;438(3):423-6. doi: 10.1007/pl00008091. PubMed PMID: 10398877.
Fukuda K, Shoda T, Morikawa H, Kato S, Mima H, Mori K. Activation of phospholipase A2 by the nociceptin receptor expressed in Chinese hamster ovary cells. J Neurochem. 1998 Nov;71(5):2186-92. doi: 10.1046/j.1471-4159.1998.71052186.x. PubMed PMID: 9798946.
Fukuda K, Kato S, Shoda T, Morikawa H, Mima H, Mori K. Partial agonistic activity of naloxone on the opioid receptors expressed from complementary deoxyribonucleic acids in Chinese hamster ovary cells. Anesth Analg. 1998 Aug;87(2):450-5. doi: 10.1097/00000539-199808000-00041. PubMed PMID: 9706949.
Morikawa H, Fukuda K, Mima H, Shoda T, Kato S, Mori K. Nociceptin receptor-mediated Ca2+ channel inhibition and its desensitization in NG108-15 cells. Eur J Pharmacol. 1998 Jun 19;351(2):247-52. doi: 10.1016/s0014-2999(98)00306-9. PubMed PMID: 9687009.
Morikawa H, Fukuda K, Mima H, Shoda T, Kato S, Mori K. Tyrosine kinase inhibitors suppress N-type and T-type Ca2+ channel currents in NG108-15 cells. Pflugers Arch. 1998 Jun;436(1):127-32. doi: 10.1007/s004240050613. PubMed PMID: 9560456.
Kato S, Fukuda K, Morikawa H, Shoda T, Mima H, Mori K. Adaptations to chronic agonist exposure of mu-opioid receptor-expressing Chinese hamster ovary cells. Eur J Pharmacol. 1998 Mar 19;345(2):221-8. doi: 10.1016/s0014-2999(98)00023-5. PubMed PMID: 9600641.
Morikawa H, Fukuda K, Mima H, Shoda T, Kato S, Mori K. Desensitization and resensitization of delta-opioid receptor-mediated Ca2+ channel inhibition in NG108-15 cells. Br J Pharmacol. 1998 Mar;123(6):1111-8. doi: 10.1038/sj.bjp.0701733. PubMed PMID: 9559894; PubMed Central PMCID: PMC1565280.
Mima H, Morikawa H, Fukuda K, Kato S, Shoda T, Mori K. Ca2+ channel inhibition by endomorphins via the cloned mu-opioid receptor expressed in NG108-15 cells. Eur J Pharmacol. 1997 Dec 11;340(2-3):R1-2. PubMed PMID: 9537802.
Fukuda K, Shoda T, Morikawa H, Kato S, Mori K. Activation of mitogen-activated protein kinase by the nociceptin receptor expressed in Chinese hamster ovary cells. FEBS Lett. 1997 Jul 28;412(2):290-4. doi: 10.1016/s0014-5793(97)00815-6. PubMed PMID: 9256237.
Noda M, Ishizaka N, Yokoyama S, Hoshi N, Kimura Y, Hashii M, Taketo M, Egorova A, Knijnik R, Fukuda K, Morikawa H, Brown DA, Higashida H. Inositol trisphosphate/Ca2+ as messengers of bradykinin B2 and muscarinic acetylcholine m1-m4 receptors in neuroblastoma-derived hybrid cells. J Lipid Mediat Cell Signal. 1996 Sep;14(1-3):175-85. doi: 10.1016/0929-7855(96)00523-8. Review. PubMed PMID: 8906560.
Fukuda K, Kato S, Morikawa H, Shoda T, Mori K. Functional coupling of the delta-, mu-, and kappa-opioid receptors to mitogen-activated protein kinase and arachidonate release in Chinese hamster ovary cells. J Neurochem. 1996 Sep;67(3):1309-16. doi: 10.1046/j.1471-4159.1996.67031309.x. PubMed PMID: 8752140.
Morikawa H, Fukuda K, Kato S, Mori K, Higashida H. Coupling of the cloned mu-opioid receptor with the omega-conotoxin-sensitive Ca2+ current in NG108-15 cells. J Neurochem. 1995 Sep;65(3):1403-6. doi: 10.1046/j.1471-4159.1995.65031403.x. PubMed PMID: 7643119.
Morikawa H, Mima H, Fujita H, Mishima S. Oxygen embolism due to hydrogen peroxide irrigation during cervical spinal surgery. Can J Anaesth. 1995 Mar;42(3):231-3. doi: 10.1007/BF03010684. PubMed PMID: 7743577.
Morikawa H, Hirota K, Kito K, Fujita H, Mishima S. Re-expansion pulmonary oedema following removal of intrathoracic haematoma. Acta Anaesthesiol Scand. 1994 Jul;38(5):518-20. doi: 10.1111/j.1399-6576.1994.tb03940.x. PubMed PMID: 7941949.

Awards

1994 – 1997 Japan Scholarship Foundation Predoctoral Scholarship, Cellular and molecular investigation of opioid receptors
1998 – 1999 Ministry of Education, Science and Culture of Japan, Grant-in-Aid for Scientific Research, Cellular and molecular mechanism of opioid tolerance
1999 – 2000 Uehara Memorial Foundation Postdoctoral Fellowship, Opioid action on midbrain dopamine neurons