MORIKAWA, HITOSHI

Hitoshi Morikawa

Associate Professor, Associate Professor (Medical)
Department of Neuroscience, Waggoner Center for Alcohol and Addiction Research


Neurobiology of reward-based learning and addiction.

morikawa@austin.utexas.edu

Phone: 512-232-9299

Office Location
PAT 402

Postal Address
The University of Texas at Austin
Department of Neuroscience, College of Natural Sciences
1 University Station C7000
Austin, TX 78712

After obtaining an M.D. from Kyoto University in Japan and completing his clinical training in anesthesiology, Dr. Morikawa became interested in basic research. His work focused on morphine and other opiates as analgesic drugs, more specifically on the cellular mechanism of tolerance after prolonged treatment with opiates. After obtaining a Ph.D. 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. His current research at The Universtiy of Texas at Austin focuses on synaptic plasticity and neuroadaptations involved in reward-based conditioning and the development of drug addiction and alcoholism.

Dr. Morikawa has established an active lab currently supporting three graduate students and three postdoctoral fellows. He is funded by two NIH RO1 grants. Dr. Morikawa was promoted to Associate Professor in 2008.

Research Summary:

A large amount of knowledge has accumulated over the past decades implicating the central dopaminergic system in reward-based reinforcement learning, decision making, motivation and locomotion, as well as its dysfunction in the etiology of a variety of neuropsychiatric disorders, such as drug addiction, schizophrenia and Parkinson disease. However, the exact neural mechanisms regulating the functional output of this system are not fully understood and treatments for the disorders described above remain far from ideal. Thus, the overall goal of my research is to advance our understanding of the physiology and pathophysiology of the central dopaminergic system at the cellular, synaptic and local circuit levels. To achieve this goal, my lab employs in vitro brain slice electrophysiology, confocal fluorescence imaging and UV photolysis of caged compounds, combined with behavioral analysis and pharmacological manipulations of specific brain areas.

People start to take addictive drugs to experience elevation or alteration in mood ("highs"). However, after repeated use of drugs, the drug-seeking and drug-taking behaviors get out of control and become compulsive, which is the defining feature of drug addiction. Dr. Hitoshi Morikawa's lab studies the brain circuits involved in the acute actions of drugs and the plastic changes in the circuits that are responsible for the development of addiction.

This lab specifically focuses on the dopaminergic neurons in the ventral midbrain. They are activated by the perception and expectation of rewards. Therefore, the dopaminergic projections from the midbrain to the limbic structures constitute an endogenous reward circuit. Behaviors that lead to the enhancement of dopamine release in this brain reward circuit tend to be repeated (reinforced). Addictive drugs induce stronger stimulation of dopaminergic transmission than almost any natural reinforcers (food, sex, etc). Thus, drugs are repeatedly used (abused) in vulnerable individuals, which will lead to plastic changes in the reward circuit.

The amount and temporal profile of dopamine release is controlled by the firing pattern of dopamine neurons, which is determined by the interaction of their intrinsic membrane properties and the afferent inputs they receive from other neurons. Accordingly, we make detailed analyses of the influence of addictive drugs on membrane ionic conductances and neurotransmitter inputs of dopamine neurons, and investigate the resulting alteration in the firing pattern. We use brain slices because they retain intact synaptic connections that are necessary for these studies. Brain slices are obtained from drug-naïve animals and animals that are chronically treated with drugs to elucidate the plastic changes induced by repeated exposure to drugs in vivo. Technically, we perform patch clamp electrophysiological recordings combined with confocal fluorescent imaging of intracellular ions. These methods will allow us to delineate the cellular events that determine the excitability of neurons with a preciseness that could not be attained by other conventional techniques. Therefore, this lab offers an ideal system to link the behavior of certain types of central neurons to that of a whole organism.

2017 Gantz S, Ford CP, Morikawa H, Williams JT, The evolving understanding of dopamine neurons in the Substantia Nigra and Ventral Tegmental Area. Annu Rev Physiol (in press)

2017 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 12:e0183685

2017 Ponomarev I, Stelly CE, Morikawa H, Blednov YA, Mayfield RD, Harris RA, Mechanistic insights into epigenetic modulation of ethanol consumption. Alcohol 60:95-101

2016 Stelly CE, Pomrenze MB, Cook JB, Morikawa H, Repeated social defeat stress enhances glutamatergic synaptic plasticity in the VTA and cocaine place conditioning. eLife 5:e15448

2016 Swapna I, Bondy B, Morikawa H, Differential dopamine regulation of Ca2+ signaling and its timing dependence in the nucleus accumbens, Cell Reports 15: 563-573

2016 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 21: 394-402

2013 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 33: 2697-2708

2013 Whitaker LR, Degoulet M, Morikawa H, Social deprivation enhances VTA synaptic plasticity and drug-induced contextual learning, Neuron 77: 335-345

2012 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 67: 223-232 

2012 Beatty JA, Sullivan MA, Morikawa H, Wilson CJ , Complex autonomous firing patterns of striatal low-threshold spike interneuron, J Neurophysiol 108: 771-781

2011 Morikawa H, Paladini CA, Dynamic regulation of midbrain dopamine neuron activity: Intrinsic, synaptic, and plasticity mechanisms, Neuroscience 198: 95-111 

2011 Bernier BE, Whitaker LR, Morikawa H, Previous ethanol experience enhances synaptic plasticity of NMDA receptors in the ventral tegmental area, J Neurosci 31: 5205-5212

2011 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 25: S92-S105 

2011 Morikawa H, Harris RA, Small K channels: Big targets for treating alcoholism?, Biol Psychiatry 69: 614-615

2011 Perra S, Clements MA, Bernier BE, Morikawa H, In vivo ethanol experience increases D2 autoinhibition in the ventral tegmental area, Neuropsychopharmacology 36: 993-1002 

2011 Theile JW, Morikawa H, Gonzales RA, Morrisett RA, GABAergic transmission modulates ethanol excitation of ventral tegmental area dopamine neurons, Neuroscience 172: 94-103

2010 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 91: 235-288

2010 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 30: 6689-6699

2009 Harnett MT, Bernier BE, Ahn KC, Morikawa H, Burst timing-dependent plasticity of NMDA receptor-mediated transmission in midbrain dopamine neurons, Neuron 62: 826-838

2009 Theile JW, Morikawa H, Gonzales RA, Morrisett RA, Role of 5-HT2C receptors in Ca2+-dependent ethanol potentiation of GABA release onto ventral tegmental area dopamine neurons, J Pharmacol Exp Ther 329: 625-633

2008 Sullivan MA, Chen H, Morikawa H, Recurrent inhibitory network among striatal cholinergic interneurons, J Neurosci 27: 8682-8690

2008 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 32: 1040-1048

2007 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 dopamine neurons, J Neurosci 27: 4776-4785

2006 Ponomarev I, Maiya R, Harnett MT, Schafer GL, Ryabinin AE, Blednov YA, Morikawa H, Boehm SL II, Homanics GE, Berman A, Lodowski KH, Bergeson SE, Harris RA, Transcriptional signatures of cellular plasticity in mice lacking the alpha1 subunit of GABAA receptors, J Neurosci 26: 5673-5683

2006 Okamoto T, Hanett MT, Morikawa H, Hyperpolarization-activated cation current (Ih) is an ethanol target in midbrain dopamine neurons of mice, J Neurophysiol 95: 619-626

2004 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 24: 11079-11087

  • 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