Developmental impact of glutamate transporter overexpression on dopaminergic neuron activity and stereotypic behavior.
Journal
Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
received:
05
06
2021
accepted:
16
12
2021
revised:
30
10
2021
pubmed:
22
1
2022
medline:
18
5
2022
entrez:
21
1
2022
Statut:
ppublish
Résumé
Obsessive-compulsive disorder (OCD) is a disabling condition that often begins in childhood. Genetic studies in OCD have pointed to SLC1A1, which encodes the neuronal glutamate transporter EAAT3, with evidence suggesting that increased expression contributes to risk. In mice, midbrain Slc1a1 expression supports repetitive behavior in response to dopaminergic agonists, aligning with neuroimaging and pharmacologic challenge studies that have implicated the dopaminergic system in OCD. These findings suggest that Slc1a1 may contribute to compulsive behavior through altered dopaminergic transmission; however, this theory has not been mechanistically tested. To examine the developmental impact of Slc1a1 overexpression on compulsive-like behaviors, we, therefore, generated a novel mouse model to perform targeted, reversible overexpression of Slc1a1 in dopaminergic neurons. Mice with life-long overexpression of Slc1a1 showed a significant increase in amphetamine (AMPH)-induced stereotypy and hyperlocomotion. Single-unit recordings demonstrated that Slc1a1 overexpression was associated with increased firing of dopaminergic neurons. Furthermore, dLight1.1 fiber photometry showed that these behavioral abnormalities were associated with increased dorsal striatum dopamine release. In contrast, no impact of overexpression was observed on anxiety-like behaviors or SKF-38393-induced grooming. Importantly, overexpression solely in adulthood failed to recapitulate these behavioral phenotypes, suggesting that overexpression during development is necessary to generate AMPH-induced phenotypes. However, doxycycline-induced reversal of Slc1a1/EAAT3 overexpression in adulthood normalized both the increased dopaminergic firing and AMPH-induced responses. These data indicate that the pathologic effects of Slc1a1/EAAT3 overexpression on dopaminergic neurotransmission and AMPH-induced stereotyped behavior are developmentally mediated, and support normalization of EAAT3 activity as a potential treatment target for basal ganglia-mediated repetitive behaviors.
Identifiants
pubmed: 35058566
doi: 10.1038/s41380-021-01424-3
pii: 10.1038/s41380-021-01424-3
pmc: PMC9106836
mid: NIHMS1765374
doi:
Substances chimiques
Excitatory Amino Acid Transporter 3
0
Slc1a1 protein, mouse
0
Dopamine
VTD58H1Z2X
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1515-1526Subventions
Organisme : NIMH NIH HHS
ID : R01 MH068073
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH114296
Pays : United States
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature Limited.
Références
Association AP Diagnostic and statistical manual of mental disorders (DSM-5®): American Psychiatric Pub; 2013.
Ruscio AM, Stein DJ, Chiu WT, Kessler RC. The epidemiology of obsessive-compulsive disorder in the National Comorbidity Survey Replication. Mol Psychiatry. 2010;15:53–63.
pubmed: 18725912
doi: 10.1038/mp.2008.94
Organization WH Depression and other common mental disorders: global health estimates. World Health Organization; 2017.
Ost LG, Havnen A, Hansen B, Kvale G. Cognitive behavioral treatments of obsessive-compulsive disorder. A systematic review and meta-analysis of studies published 1993-2014. Clin Psychol Rev. 2015;40:156–69.
pubmed: 26117062
doi: 10.1016/j.cpr.2015.06.003
Soomro GM, Altman D, Rajagopal S, Oakley-Browne M. Selective serotonin re-uptake inhibitors (SSRIs) versus placebo for obsessive compulsive disorder (OCD). Cochrane Database Syst Rev. 2008;1:CD001765.
Bloch MH, McGuire J, Landeros-Weisenberger A, Leckman JF, Pittenger C. Meta-analysis of the dose-response relationship of SSRI in obsessive-compulsive disorder. Mol Psychiatry. 2010;15:850–5.
pubmed: 19468281
doi: 10.1038/mp.2009.50
Bollini P, Pampallona S, Tibaldi G, Kupelnick B, Munizza C. Effectiveness of antidepressants. Meta-analysis of dose-effect relationships in randomised clinical trials. Br J Psychiatry. 1999;174:297–303.
pubmed: 10533547
doi: 10.1192/bjp.174.4.297
Meier SM, Petersen L, Schendel DE, Mattheisen M, Mortensen PB, Mors O. Obsessive-compulsive disorder and autism spectrum disorders: longitudinal and offspring risk. PLoS One. 2015;10:e0141703.
pubmed: 26558765
pmcid: 4641696
doi: 10.1371/journal.pone.0141703
Lebowitz ER, Motlagh MG, Katsovich L, King RA, Lombroso PJ, Grantz H, et al. Tourette syndrome in youth with and without obsessive compulsive disorder and attention deficit hyperactivity disorder. Eur Child Adolesc Psychiatry. 2012;21:451–7.
pubmed: 22543961
pmcid: 3722559
doi: 10.1007/s00787-012-0278-5
Ivarsson T, Melin K, Wallin L. Categorical and dimensional aspects of co-morbidity in obsessive-compulsive disorder (OCD). Eur Child Adolesc Psychiatry. 2008;17:20–31.
pubmed: 18004647
doi: 10.1007/s00787-007-0626-z
Zohar AH. The epidemiology of obsessive-compulsive disorder in children and adolescents. Child Adolesc Psychiatr Clin N. Am. 1999;8:445–60.
pubmed: 10442225
doi: 10.1016/S1056-4993(18)30163-9
Haber SN, Heilbronner SR. Translational research in OCD: circuitry and mechanisms. Neuropsychopharmacology 2013;38:252–3.
pubmed: 23147494
doi: 10.1038/npp.2012.182
Ahmari SE, Dougherty DD. Dissecting Ocd Circuits: From Animal Models to Targeted Treatments. Depress Anxiety. 2015;32:550–62.
pubmed: 25952989
pmcid: 4515165
doi: 10.1002/da.22367
Vicente AM, Martins GJ, Costa RM. Cortico-basal ganglia circuits underlying dysfunctional control of motor behaviors in neuropsychiatric disorders. Curr Opin Genet Dev. 2020;65:151–9.
pubmed: 32688249
pmcid: 7749078
doi: 10.1016/j.gde.2020.05.042
Boedhoe PS, Schmaal L, Abe Y, Ameis SH, Arnold PD, Batistuzzo MC, et al. Distinct subcortical volume alterations in pediatric and adult OCD: a worldwide meta- and mega-analysis. Am J Psychiatry. 2017;174:60–9.
pubmed: 27609241
doi: 10.1176/appi.ajp.2016.16020201
Rosenberg DR, Keshavan MS, O’Hearn KM, Dick EL, Bagwell WW, Seymour AB, et al. Frontostriatal measurement in treatment-naive children with obsessive-compulsive disorder. Arch Gen Psychiatry. 1997;54:824–30.
pubmed: 9294373
doi: 10.1001/archpsyc.1997.01830210068007
Robinson D, Wu H, Munne RA, Ashtari M, Alvir JM, Lerner G, et al. Reduced caudate nucleus volume in obsessive-compulsive disorder. Arch Gen Psychiatry. 1995;52:393–8.
pubmed: 7726720
doi: 10.1001/archpsyc.1995.03950170067009
Plessen KJ, Bansal R, Peterson BS. Imaging evidence for anatomical disturbances and neuroplastic compensation in persons with Tourette syndrome. J Psychosom Res. 2009;67:559–73.
pubmed: 19913660
pmcid: 4283588
doi: 10.1016/j.jpsychores.2009.07.005
Wan X, Zhang S, Wang W, Su X, Li J, Yang X, et al. Gray matter abnormalities in Tourette Syndrome: a meta-analysis of voxel-based morphometry studies. Transl Psychiatry. 2021;11:287.
pubmed: 33990537
pmcid: 8121885
doi: 10.1038/s41398-021-01394-8
Baxter LR Jr, Phelps ME, Mazziotta JC, Guze BH, Schwartz JM, Selin CE. Local cerebral glucose metabolic rates in obsessive-compulsive disorder. A comparison with rates in unipolar depression and in normal controls. Arch Gen Psychiatry. 1987;44:211–8.
pubmed: 3493749
doi: 10.1001/archpsyc.1987.01800150017003
Swedo SE, Schapiro MB, Grady CL, Cheslow DL, Leonard HL, Kumar A, et al. Cerebral glucose metabolism in childhood-onset obsessive-compulsive disorder. Arch Gen Psychiatry. 1989;46:518–23.
pubmed: 2786402
doi: 10.1001/archpsyc.1989.01810060038007
Peterson BS, Skudlarski P, Anderson AW, Zhang H, Gatenby JC, Lacadie CM, et al. A functional magnetic resonance imaging study of tic suppression in Tourette syndrome. Arch Gen Psychiatry. 1998;55:326–33.
pubmed: 9554428
doi: 10.1001/archpsyc.55.4.326
Breiter HC, Rauch SL, Kwong KK, Baker JR, Weisskoff RM, Kennedy DN, et al. Functional magnetic resonance imaging of symptom provocation in obsessive-compulsive disorder. Arch Gen Psychiatry. 1996;53:595–606.
pubmed: 8660126
doi: 10.1001/archpsyc.1996.01830070041008
Rauch SL, Jenike MA, Alpert NM, Baer L, Breiter HC, Savage CR, et al. Regional cerebral blood flow measured during symptom provocation in obsessive-compulsive disorder using oxygen 15-labeled carbon dioxide and positron emission tomography. Arch Gen Psychiatry. 1994;51:62–70.
pubmed: 8279930
doi: 10.1001/archpsyc.1994.03950010062008
Worbe Y, Malherbe C, Hartmann A, Pelegrini-Issac M, Messe A, Vidailhet M, et al. Functional immaturity of cortico-basal ganglia networks in Gilles de la Tourette syndrome. Brain 2012;135:1937–46.
pubmed: 22434213
doi: 10.1093/brain/aws056
Guehl D, Benazzouz A, Aouizerate B, Cuny E, Rotge JY, Rougier A, et al. Neuronal correlates of obsessions in the caudate nucleus. Biol Psychiatry. 2008;63:557–62.
pubmed: 17945196
doi: 10.1016/j.biopsych.2007.06.023
Welter ML, Burbaud P, Fernandez-Vidal S, Bardinet E, Coste J, Piallat B, et al. Basal ganglia dysfunction in OCD: subthalamic neuronal activity correlates with symptoms severity and predicts high-frequency stimulation efficacy. Transl Psychiatry. 2011;1:e5.
pubmed: 22832400
pmcid: 3309476
doi: 10.1038/tp.2011.5
Priori A, Giannicola G, Rosa M, Marceglia S, Servello D, Sassi M, et al. Deep brain electrophysiological recordings provide clues to the pathophysiology of Tourette syndrome. Neurosci Biobehav Rev. 2013;37:1063–8.
pubmed: 23333267
doi: 10.1016/j.neubiorev.2013.01.011
Zhuang P, Hallett M, Zhang X, Li J, Zhang Y, Li Y. Neuronal activity in the globus pallidus internus in patients with tics. J Neurol Neurosurg Psychiatry. 2009;80:1075–81.
pubmed: 19279028
doi: 10.1136/jnnp.2008.161869
Marceglia S, Servello D, Foffani G, Porta M, Sassi M, Mrakic-Sposta S, et al. Thalamic single-unit and local field potential activity in Tourette syndrome. Mov Disord. 2010;25:300–8.
pubmed: 20108375
doi: 10.1002/mds.22982
Shakeri J, Farnia V, Karimi AR, Tatari F, Juibari TA, Alikhani M, et al. The prevalence and clinical features of amphetamine-induced obsessive compulsive disorder. Drug Alcohol Depend. 2016;160:157–62.
pubmed: 26811120
doi: 10.1016/j.drugalcdep.2015.12.034
Voon V, Fernagut PO, Wickens J, Baunez C, Rodriguez M, Pavon N, et al. Chronic dopaminergic stimulation in Parkinson’s disease: from dyskinesias to impulse control disorders. Lancet Neurol. 2009;8:1140–9.
pubmed: 19909912
doi: 10.1016/S1474-4422(09)70287-X
Baldan LC, Williams KA, Gallezot JD, Pogorelov V, Rapanelli M, Crowley M, et al. Histidine decarboxylase deficiency causes tourette syndrome: parallel findings in humans and mice. Neuron 2014;81:77–90.
pubmed: 24411733
pmcid: 3894588
doi: 10.1016/j.neuron.2013.10.052
Madruga-Garrido M, Mir P. Tics and other stereotyped movements as side effects of pharmacological treatment. Int Rev Neurobiol. 2013;112:481–94.
pubmed: 24295631
doi: 10.1016/B978-0-12-411546-0.00016-0
Leckman JF, Bloch MH, Smith ME, Larabi D, Hampson M. Neurobiological substrates of Tourette’s disorder. J Child Adolesc Psychopharmacol. 2010;20:237–47.
pubmed: 20807062
pmcid: 2958453
doi: 10.1089/cap.2009.0118
Shale H, Fahn S, Mayeux R. Tics in a patient with Parkinson’s disease. Mov Disord. 1986;1:79–83.
pubmed: 3504234
doi: 10.1002/mds.870010111
Denys D, van der Wee N, Janssen J, De Geus F, Westenberg HG. Low level of dopaminergic D2 receptor binding in obsessive-compulsive disorder. Biol Psychiatry. 2004;55:1041–5.
pubmed: 15121489
doi: 10.1016/j.biopsych.2004.01.023
Perani D, Garibotto V, Gorini A, Moresco RM, Henin M, Panzacchi A, et al. In vivo PET study of 5HT(2A) serotonin and D(2) dopamine dysfunction in drug-naive obsessive-compulsive disorder. Neuroimage 2008;42:306–14.
pubmed: 18511303
doi: 10.1016/j.neuroimage.2008.04.233
Hienert M, Gryglewski G, Stamenkovic M, Kasper S, Lanzenberger R. Striatal dopaminergic alterations in Tourette’s syndrome: a meta-analysis based on 16 PET and SPECT neuroimaging studies. Transl Psychiatry. 2018;8:143.
pubmed: 30072700
pmcid: 6072751
doi: 10.1038/s41398-018-0202-y
Marsh R, Pagliaccio D, Fitzgerald K, Neuromelanin-Sensitive MRI. as a Marker of Dopamine Hyperactivity and CBT Response in Children With Obsessive-Compulsive Disorder. Biol Psychiatry 2021;89:S79–S80. 9, Supplement
doi: 10.1016/j.biopsych.2021.02.212
Singer HS, Szymanski S, Giuliano J, Yokoi F, Dogan AS, Brasic JR, et al. Elevated intrasynaptic dopamine release in Tourette’s syndrome measured by PET. Am J Psychiatry. 2002;159:1329–36.
pubmed: 12153825
doi: 10.1176/appi.ajp.159.8.1329
Ernst M, Zametkin AJ, Jons PH, Matochik JA, Pascualvaca D, Cohen RM. High presynaptic dopaminergic activity in children with Tourette’s disorder. J Am Acad Child Adolesc Psychiatry. 1999;38:86–94.
pubmed: 9893421
doi: 10.1097/00004583-199901000-00024
Bloch MH, Landeros-Weisenberger A, Kelmendi B, Coric V, Bracken MB, Leckman JF. A systematic review: antipsychotic augmentation with treatment refractory obsessive-compulsive disorder. Mol Psychiatry. 2006;11:622–32.
pubmed: 16585942
doi: 10.1038/sj.mp.4001823
Albert U, Carmassi C, Cosci F, De Cori D, Di Nicola M, Ferrari S, et al. Role and clinical implications of atypical antipsychotics in anxiety disorders, obsessive-compulsive disorder, trauma-related, and somatic symptom disorders: a systematized review. Int Clin Psychopharmacol. 2016;31:249–58.
pubmed: 26974213
doi: 10.1097/YIC.0000000000000127
Robertson MM, Eapen V, Singer HS, Martino D, Scharf JM, Paschou P, et al. Gilles de la Tourette syndrome. Nat Rev Dis Prim. 2017;3:16097.
pubmed: 28150698
doi: 10.1038/nrdp.2016.97
Du JC, Chiu TF, Lee KM, Wu HL, Yang YC, Hsu SY, et al. Tourette syndrome in children: an updated review. Pediatr Neonatol. 2010;51:255–64.
pubmed: 20951354
doi: 10.1016/S1875-9572(10)60050-2
Burguiere E, Monteiro P, Mallet L, Feng G, Graybiel AM. Striatal circuits, habits, and implications for obsessive-compulsive disorder. Curr Opin Neurobiol. 2015;30:59–65.
pubmed: 25241072
doi: 10.1016/j.conb.2014.08.008
Kalueff AV, Stewart AM, Song C, Berridge KC, Graybiel AM, Fentress JC. Neurobiology of rodent self-grooming and its value for translational neuroscience. Nat Rev Neurosci. 2016;17:45–59.
pubmed: 26675822
doi: 10.1038/nrn.2015.8
Pauls DL. The genetics of obsessive compulsive disorder: a review of the evidence. Am J Med Genet C Semin Med Genet. 2008;148C:133–9.
pubmed: 18412099
doi: 10.1002/ajmg.c.30168
Hanna GL, Veenstra-VanderWeele J, Cox NJ, Boehnke M, Himle JA, Curtis GC, et al. Genome-wide linkage analysis of families with obsessive-compulsive disorder ascertained through pediatric probands. Am J Med Genet. 2002;114:541–52.
pubmed: 12116192
doi: 10.1002/ajmg.10519
Willour VL, Yao Shugart Y, Samuels J, Grados M, Cullen B, Bienvenu OJ 3rd, et al. Replication study supports evidence for linkage to 9p24 in obsessive-compulsive disorder. Am J Hum Genet. 2004;75:508–13.
pubmed: 15272418
pmcid: 1182030
doi: 10.1086/423899
Veenstra-VanderWeele J, Kim SJ, Gonen D, Hanna GL, Leventhal BL, Cook EH Jr. Genomic organization of the SLC1A1/EAAC1 gene and mutation screening in early-onset obsessive-compulsive disorder. Mol Psychiatry. 2001;6:160–7.
pubmed: 11317217
doi: 10.1038/sj.mp.4000806
Dickel DE, Veenstra-VanderWeele J, Cox NJ, Wu X, Fischer DJ, Van Etten-Lee M, et al. Association testing of the positional and functional candidate gene SLC1A1/EAAC1 in early-onset obsessive-compulsive disorder. Arch Gen Psychiatry. 2006;63:778–85.
pubmed: 16818867
doi: 10.1001/archpsyc.63.7.778
Wendland JR, Moya PR, Timpano KR, Anavitarte AP, Kruse MR, Wheaton MG, et al. A haplotype containing quantitative trait loci for SLC1A1 gene expression and its association with obsessive-compulsive disorder. Arch Gen Psychiatry. 2009;66:408–16.
pubmed: 19349310
pmcid: 2775716
doi: 10.1001/archgenpsychiatry.2009.6
Arnold PD, Sicard T, Burroughs E, Richter MA, Kennedy JL. Glutamate transporter gene SLC1A1 associated with obsessive-compulsive disorder. Arch Gen Psychiatry. 2006;63:769–76.
pubmed: 16818866
doi: 10.1001/archpsyc.63.7.769
Stewart SE, Mayerfeld C, Arnold PD, Crane JR, O’Dushlaine C, Fagerness JA, et al. Meta-analysis of association between obsessive-compulsive disorder and the 3’ region of neuronal glutamate transporter gene SLC1A1. Am J Med Genet B Neuropsychiatr Genet. 2013;162B:367–79.
pubmed: 23606572
doi: 10.1002/ajmg.b.32137
Stewart SE, Yu D, Scharf JM, Neale BM, Fagerness JA, Mathews CA, et al. Genome-wide association study of obsessive-compulsive disorder. Mol Psychiatry. 2013;18:788–98.
pubmed: 22889921
doi: 10.1038/mp.2012.85
Mattheisen M, Samuels JF, Wang Y, Greenberg BD, Fyer AJ, McCracken JT, et al. Genome-wide association study in obsessive-compulsive disorder: results from the OCGAS. Mol Psychiatry. 2015;20:337–44.
pubmed: 24821223
doi: 10.1038/mp.2014.43
Underhill SM, Ingram SL, Ahmari SE, Veenstra-VanderWeele J, Amara SG. Neuronal excitatory amino acid transporter EAAT3: Emerging functions in health and disease. Neurochem Int. 2019;123:69–76.
pubmed: 29800605
doi: 10.1016/j.neuint.2018.05.012
Nieoullon A, Canolle B, Masmejean F, Guillet B, Pisano P, Lortet S. The neuronal excitatory amino acid transporter EAAC1/EAAT3: does it represent a major actor at the brain excitatory synapse? J Neurochem. 2006;98:1007–18.
pubmed: 16800850
doi: 10.1111/j.1471-4159.2006.03978.x
Li MH, Underhill SM, Reed C, Phillips TJ, Amara SG, Ingram SL. Amphetamine and Methamphetamine Increase NMDAR-GluN2B Synaptic Currents in Midbrain Dopamine Neurons. Neuropsychopharmacology 2017;42:1539–47.
pubmed: 27976681
pmcid: 5436114
doi: 10.1038/npp.2016.278
Underhill SM, Wheeler DS, Li M, Watts SD, Ingram SL, Amara SG. Amphetamine modulates excitatory neurotransmission through endocytosis of the glutamate transporter EAAT3 in dopamine neurons. Neuron 2014;83:404–16.
pubmed: 25033183
pmcid: 4159050
doi: 10.1016/j.neuron.2014.05.043
Conti F, DeBiasi S, Minelli A, Rothstein JD, Melone M. EAAC1, a high-affinity glutamate tranporter, is localized to astrocytes and gabaergic neurons besides pyramidal cells in the rat cerebral cortex. Cereb Cortex 1998;8:108–16.
pubmed: 9542890
doi: 10.1093/cercor/8.2.108
Otis TS, Brasnjo G, Dzubay JA, Pratap M. Interactions between glutamate transporters and metabotropic glutamate receptors at excitatory synapses in the cerebellar cortex. Neurochem Int. 2004;45:537–44.
pubmed: 15186920
doi: 10.1016/j.neuint.2003.11.007
Brennan BP, Rauch SL, Jensen JE, Pope HG Jr. A critical review of magnetic resonance spectroscopy studies of obsessive-compulsive disorder. Biol Psychiatry. 2013;73:24–31.
pubmed: 22831979
doi: 10.1016/j.biopsych.2012.06.023
Bhattacharyya S, Khanna S, Chakrabarty K, Mahadevan A, Christopher R, Shankar SK. Anti-brain autoantibodies and altered excitatory neurotransmitters in obsessive-compulsive disorder. Neuropsychopharmacology 2009;34:2489–96.
pubmed: 19675532
doi: 10.1038/npp.2009.77
Piantadosi SC, Chamberlain BL, Glausier JR, Lewis DA, Ahmari SE. Lower excitatory synaptic gene expression in orbitofrontal cortex and striatum in an initial study of subjects with obsessive compulsive disorder. Mol Psychiatry. 2019;26:986–98.
pubmed: 31168067
doi: 10.1038/s41380-019-0431-3
Mahone EM, Puts NA, Edden RAE, Ryan M, Singer HS. GABA and glutamate in children with Tourette syndrome: a (1)H MR spectroscopy study at 7T. Psychiatry Res Neuroimaging. 2018;273:46–53.
pubmed: 29329743
doi: 10.1016/j.pscychresns.2017.12.005
Anderson GM, Pollak ES, Chatterjee D, Leckman JF, Riddle MA, Cohen DJ. Brain monoamines and amino acids in Gilles de la Tourette’s syndrome: a preliminary study of subcortical regions. Arch Gen Psychiatry. 1992;49:584–6.
pubmed: 1378261
doi: 10.1001/archpsyc.1992.01820070078016
Abelson JF, Kwan KY, O’Roak BJ, Baek DY, Stillman AA, Morgan TM, et al. Sequence variants in SLITRK1 are associated with Tourette’s syndrome. Science 2005;310:317–20.
pubmed: 16224024
doi: 10.1126/science.1116502
Adamczyk A, Gause CD, Sattler R, Vidensky S, Rothstein JD, Singer H, et al. Genetic and functional studies of a missense variant in a glutamate transporter, SLC1A3, in Tourette syndrome. Psychiatr Genet. 2011;21:90–7.
pubmed: 21233784
doi: 10.1097/YPG.0b013e328341a307
Delgado-Acevedo C, Estay SF, Radke AK, Sengupta A, Escobar AP, Henriquez-Belmar F, et al. Behavioral and synaptic alterations relevant to obsessive-compulsive disorder in mice with increased EAAT3 expression. Neuropsychopharmacology 2019;44:1163–73.
pubmed: 30622300
doi: 10.1038/s41386-018-0302-7
Escobar AP, Martinez-Pinto J, Silva-Olivares F, Sotomayor-Zarate R, Moya PR. Altered Grooming Syntax and Amphetamine-Induced Dopamine Release in EAAT3 Overexpressing Mice. Front Cell Neurosci. 2021;15:661478.
pubmed: 34234648
pmcid: 8255620
doi: 10.3389/fncel.2021.661478
Denys D, de Vries F, Cath D, Figee M, Vulink N, Veltman DJ, et al. Dopaminergic activity in Tourette syndrome and obsessive-compulsive disorder. Eur Neuropsychopharmacol. 2013;23:1423–31.
pubmed: 23876376
doi: 10.1016/j.euroneuro.2013.05.012
Zike ID, Chohan MO, Kopelman JM, Krasnow EN, Flicker D, Nautiyal KM, et al. OCD candidate gene SLC1A1/EAAT3 impacts basal ganglia-mediated activity and stereotypic behavior. Proc Natl Acad Sci USA. 2017;114:5719–24.
pubmed: 28507136
pmcid: 5465902
doi: 10.1073/pnas.1701736114
Tanaka KF, Ahmari SE, Leonardo ED, Richardson-Jones JW, Budreck EC, Scheiffele P, et al. Flexible Accelerated STOP Tetracycline Operator-knockin (FAST): a versatile and efficient new gene modulating system. Biol Psychiatry. 2010;67:770–3.
pubmed: 20163789
pmcid: 2969181
doi: 10.1016/j.biopsych.2009.12.020
Wu Y, Wang C, Sun H, LeRoith D, Yakar S. High-efficient FLPo deleter mice in C57BL/6J background. PLoS One. 2009;4:e8054.
pubmed: 19956655
pmcid: 2777316
doi: 10.1371/journal.pone.0008054
Tillack K, Aboutalebi H, Kramer ER. An efficient and versatile system for visualization and genetic modification of dopaminergic neurons in transgenic mice. PLoS One. 2015;10:e0136203.
pubmed: 26291828
pmcid: 4546329
doi: 10.1371/journal.pone.0136203
Grace AA, Bunney BS. The control of firing pattern in nigral dopamine neurons: burst firing. J Neurosci. 1984;4:2877–90.
pubmed: 6150071
pmcid: 6564720
doi: 10.1523/JNEUROSCI.04-11-02877.1984
Ungless MA, Magill PJ, Bolam JP. Uniform inhibition of dopamine neurons in the ventral tegmental area by aversive stimuli. Science 2004;303:2040–2.
pubmed: 15044807
doi: 10.1126/science.1093360
Ungless MA, Grace AA. Are you or aren’t you? Challenges associated with physiologically identifying dopamine neurons. Trends Neurosci. 2012;35:422–30.
pubmed: 22459161
pmcid: 3383926
doi: 10.1016/j.tins.2012.02.003
Patriarchi T, Cho JR, Merten K, Howe MW, Marley A, Xiong WH, et al. Ultrafast neuronal imaging of dopamine dynamics with designed genetically encoded sensors. Science. 2018;360:eaat4422.
pubmed: 29853555
pmcid: 6287765
doi: 10.1126/science.aat4422
Martianova E, Aronson S, Proulx CD. Multi-fiber photometry to record neural activity in freely-moving animals. J Vis Exp. 2019;152:e60278.
Baudouin SJ, Gaudias J, Gerharz S, Hatstatt L, Zhou K, Punnakkal P, et al. Shared synaptic pathophysiology in syndromic and nonsyndromic rodent models of autism. Science 2012;338:128–32.
pubmed: 22983708
doi: 10.1126/science.1224159
Shinozaki Y, Shibata K, Yoshida K, Shigetomi E, Gachet C, Ikenaka K, et al. Transformation of astrocytes to a neuroprotective phenotype by microglia via P2Y1 receptor downregulation. Cell Rep. 2017;19:1151–64.
pubmed: 28494865
doi: 10.1016/j.celrep.2017.04.047
Qiu L, Rivera-Perez JA, Xu Z. A non-specific effect associated with conditional transgene expression based on Cre-loxP strategy in mice. PLoS One. 2011;6:e18778.
pubmed: 21572998
pmcid: 3091857
doi: 10.1371/journal.pone.0018778
Chohan MO, Esses S, Haft J, Ahmari S, Veenstra-VanderWeele J. Altered baseline and amphetamine-mediated behavioral profiles in dopamine transporter Cre (DAT-Ires-Cre) mice compared to tyrosine hydroxylase Cre (TH-Cre) mice. Psychopharmacology (Berl). 2020;237:3553–68.
doi: 10.1007/s00213-020-05635-4
Kramer DJ, Aisenberg EE, Kosillo P, Friedmann D, Stafford DA, Lee AY, et al. Generation of a DAT-P2A-Flpo mouse line for intersectional genetic targeting of dopamine neuron subpopulations. Cell Rep. 2021;35:109123.
pubmed: 33979604
pmcid: 8240967
doi: 10.1016/j.celrep.2021.109123
Zhuang X, Masson J, Gingrich JA, Rayport S, Hen R. Targeted gene expression in dopamine and serotonin neurons of the mouse brain. J Neurosci Methods. 2005;143:27–32.
pubmed: 15763133
doi: 10.1016/j.jneumeth.2004.09.020
Steinmetz NA, Buetfering C, Lecoq J, Lee CR, Peters AJ, Jacobs EAK, et al. Aberrant cortical activity in multiple GCaMP6-expressing transgenic mouse lines. eNeuro. 2017;4:ENEURO.0207-17.2017.
pubmed: 28932809
pmcid: 5604087
doi: 10.1523/ENEURO.0207-17.2017
Costa KM, Schenkel D, Roeper J. Sex-dependent alterations in behavior, drug responses and dopamine transporter expression in heterozygous DAT-Cre mice. Sci Rep. 2021;11:3334.
pubmed: 33558587
pmcid: 7870653
doi: 10.1038/s41598-021-82600-x
Gilani AI, Chohan MO, Inan M, Schobel SA, Chaudhury NH, Paskewitz S, et al. Interneuron precursor transplants in adult hippocampus reverse psychosis-relevant features in a mouse model of hippocampal disinhibition. Proc Natl Acad Sci USA. 2014;111:7450–5.
pubmed: 24794528
pmcid: 4034251
doi: 10.1073/pnas.1316488111
Welch JM, Lu J, Rodriguiz RM, Trotta NC, Peca J, Ding JD, et al. Cortico-striatal synaptic defects and OCD-like behaviours in Sapap3-mutant mice. Nature 2007;448:894–900.
pubmed: 17713528
pmcid: 2442572
doi: 10.1038/nature06104
Bienvenu OJ, Wang Y, Shugart YY, Welch JM, Grados MA, Fyer AJ, et al. Sapap3 and pathological grooming in humans: Results from the OCD collaborative genetics study. Am J Med Genet B Neuropsychiatr Genet. 2009;150B:710–20.
pubmed: 19051237
doi: 10.1002/ajmg.b.30897
Gonzalez LF, Henriquez-Belmar F, Delgado-Acevedo C, Cisternas-Olmedo M, Arriagada G, Sotomayor-Zarate R, et al. Neurochemical and behavioral characterization of neuronal glutamate transporter EAAT3 heterozygous mice. Biol Res. 2017;50:29.
pubmed: 28927446
pmcid: 5605982
doi: 10.1186/s40659-017-0138-3
Mathews GC, Diamond JS. Neuronal glutamate uptake Contributes to GABA synthesis and inhibitory synaptic strength. J Neurosci. 2003;23:2040–8.
pubmed: 12657662
pmcid: 6742021
doi: 10.1523/JNEUROSCI.23-06-02040.2003
Sepkuty JP, Cohen AS, Eccles C, Rafiq A, Behar K, Ganel R, et al. A neuronal glutamate transporter contributes to neurotransmitter GABA synthesis and epilepsy. J Neurosci. 2002;22:6372–9.
pubmed: 12151515
pmcid: 2483507
doi: 10.1523/JNEUROSCI.22-15-06372.2002
Taniguchi H, He M, Wu P, Kim S, Paik R, Sugino K, et al. A resource of Cre driver lines for genetic targeting of GABAergic neurons in cerebral cortex. Neuron 2011;71:995–1013.
pubmed: 21943598
pmcid: 3779648
doi: 10.1016/j.neuron.2011.07.026
Nathanson JL, Jappelli R, Scheeff ED, Manning G, Obata K, Brenner S, et al. Short promoters in viral vectors drive selective expression in mammalian inhibitory neurons, but do not restrict activity to specific inhibitory cell-types. Front Neural Circuits. 2009;3:19.
pubmed: 19949461
pmcid: 2783723
doi: 10.3389/neuro.04.019.2009
Lahti L, Achim K, Partanen J. Molecular regulation of GABAergic neuron differentiation and diversity in the developing midbrain. Acta Physiol (Oxf). 2013;207:616–27.
doi: 10.1111/apha.12062
Savitt JM, Jang SS, Mu W, Dawson VL, Dawson TM. Bcl-x is required for proper development of the mouse substantia nigra. J Neurosci. 2005;25:6721–8.
pubmed: 16033881
pmcid: 6725345
doi: 10.1523/JNEUROSCI.0760-05.2005
Backman CM, Malik N, Zhang Y, Shan L, Grinberg A, Hoffer BJ, et al. Characterization of a mouse strain expressing Cre recombinase from the 3’ untranslated region of the dopamine transporter locus. Genesis 2006;44:383–90.
pubmed: 16865686
doi: 10.1002/dvg.20228
Aoyama K, Suh SW, Hamby AM, Liu J, Chan WY, Chen Y, et al. Neuronal glutathione deficiency and age-dependent neurodegeneration in the EAAC1 deficient mouse. Nat Neurosci. 2006;9:119–26.
pubmed: 16311588
doi: 10.1038/nn1609
Berman AE, Chan WY, Brennan AM, Reyes RC, Adler BL, Suh SW, et al. N-acetylcysteine prevents loss of dopaminergic neurons in the EAAC1-/- mouse. Ann Neurol. 2011;69:509–20.
pubmed: 21446024
doi: 10.1002/ana.22162
Marvin JS, Scholl B, Wilson DE, Podgorski K, Kazemipour A, Muller JA, et al. Stability, affinity, and chromatic variants of the glutamate sensor iGluSnFR. Nat Methods. 2018;15:936–9.
pubmed: 30377363
pmcid: 6394230
doi: 10.1038/s41592-018-0171-3
Rothmond DA, Weickert CS, Webster MJ. Developmental changes in human dopamine neurotransmission: cortical receptors and terminators. BMC Neurosci. 2012;13:18.
pubmed: 22336227
pmcid: 3315415
doi: 10.1186/1471-2202-13-18
Naneix F, Marchand AR, Di Scala G, Pape JR, Coutureau E. Parallel maturation of goal-directed behavior and dopaminergic systems during adolescence. J Neurosci. 2012;32:16223–32.
pubmed: 23152606
pmcid: 6794026
doi: 10.1523/JNEUROSCI.3080-12.2012
Powell SB, Khan A, Young JW, Scott CN, Buell MR, Caldwell S, et al. Early adolescent emergence of reversal learning impairments in isolation-reared rats. Dev Neurosci. 2015;37:253–62.
pubmed: 26022788
doi: 10.1159/000430091
Radke AK, Kocharian A, Covey DP, Lovinger DM, Cheer JF, Mateo Y, et al. Contributions of nucleus accumbens dopamine to cognitive flexibility. Eur J Neurosci. 2019;50:2023–35.
pubmed: 30218623
doi: 10.1111/ejn.14152
Ragozzino ME, Ragozzino KE, Mizumori SJ, Kesner RP. Role of the dorsomedial striatum in behavioral flexibility for response and visual cue discrimination learning. Behav Neurosci. 2002;116:105–15.
pubmed: 11898801
pmcid: 3273324
doi: 10.1037/0735-7044.116.1.105
Mar AC, Horner AE, Nilsson SR, Alsio J, Kent BA, Kim CH, et al. The touchscreen operant platform for assessing executive function in rats and mice. Nat Protoc. 2013;8:1985–2005.
pubmed: 24051960
pmcid: 4131754
doi: 10.1038/nprot.2013.123
Takeuchi T, Duszkiewicz AJ, Sonneborn A, Spooner PA, Yamasaki M, Watanabe M, et al. Locus coeruleus and dopaminergic consolidation of everyday memory. Nature 2016;537:357–62.
pubmed: 27602521
pmcid: 5161591
doi: 10.1038/nature19325
McNamara CG, Tejero-Cantero A, Trouche S, Campo-Urriza N, Dupret D. Dopaminergic neurons promote hippocampal reactivation and spatial memory persistence. Nat Neurosci. 2014;17:1658–60.
pubmed: 25326690
pmcid: 4241115
doi: 10.1038/nn.3843
Schiemann J, Schlaudraff F, Klose V, Bingmer M, Seino S, Magill PJ, et al. K-ATP channels in dopamine substantia nigra neurons control bursting and novelty-induced exploration. Nat Neurosci. 2012;15:1272–80.
pubmed: 22902720
pmcid: 4242970
doi: 10.1038/nn.3185
Schultz W, Dayan P, Montague PR. A neural substrate of prediction and reward. Science 1997;275:1593–9.
pubmed: 9054347
doi: 10.1126/science.275.5306.1593
Legault M, Wise RA. Novelty-evoked elevations of nucleus accumbens dopamine: dependence on impulse flow from the ventral subiculum and glutamatergic neurotransmission in the ventral tegmental area. Eur J Neurosci. 2001;13:819–28.
pubmed: 11207817
doi: 10.1046/j.0953-816x.2000.01448.x
Zweifel LS, Fadok JP, Argilli E, Garelick MG, Jones GL, Dickerson TM, et al. Activation of dopamine neurons is critical for aversive conditioning and prevention of generalized anxiety. Nat Neurosci. 2011;14:620–6.
pubmed: 21499253
pmcid: 3083461
doi: 10.1038/nn.2808
Bananej M, Karimi-Sori A, Zarrindast MR, Ahmadi S. D1 and D2 dopaminergic systems in the rat basolateral amygdala are involved in anxiogenic-like effects induced by histamine. J Psychopharmacol. 2012;26:564–74.
pubmed: 21628344
doi: 10.1177/0269881111405556
Berman SM, Kuczenski R, McCracken JT, London ED. Potential adverse effects of amphetamine treatment on brain and behavior: a review. Mol Psychiatry. 2009;14:123–42.
pubmed: 18698321
doi: 10.1038/mp.2008.90
Kienast T, Hariri AR, Schlagenhauf F, Wrase J, Sterzer P, Buchholz HG, et al. Dopamine in amygdala gates limbic processing of aversive stimuli in humans. Nat Neurosci. 2008;11:1381–2.
pubmed: 18978778
doi: 10.1038/nn.2222
Wang X, Zhang C, Szabo G, Sun QQ. Distribution of CaMKIIalpha expression in the brain in vivo, studied by CaMKIIalpha-GFP mice. Brain Res. 2013;1518:9–25.
pubmed: 23632380
pmcid: 3747672
doi: 10.1016/j.brainres.2013.04.042
Cook SG, Bourke AM, O’Leary H, Zaegel V, Lasda E, Mize-Berge J, et al. Analysis of the CaMKIIalpha and beta splice-variant distribution among brain regions reveals isoform-specific differences in holoenzyme formation. Sci Rep. 2018;8:5448.
pubmed: 29615706
pmcid: 5882894
doi: 10.1038/s41598-018-23779-4
Ercan-Sencicek AG, Stillman AA, Ghosh AK, Bilguvar K, O’Roak BJ, Mason CE, et al. L-histidine decarboxylase and Tourette’s syndrome. N. Engl J Med. 2010;362:1901–8.
pubmed: 20445167
pmcid: 2894694
doi: 10.1056/NEJMoa0907006
Horiuchi Y, Iida S, Koga M, Ishiguro H, Iijima Y, Inada T, et al. Association of SNPs linked to increased expression of SLC1A1 with schizophrenia. Am J Med Genet B Neuropsychiatr Genet. 2012;159B:30–7.
pubmed: 22095641
doi: 10.1002/ajmg.b.31249
Pardinas AF, Holmans P, Pocklington AJ, Escott-Price V, Ripke S, Carrera N, et al. Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection. Nat Genet. 2018;50:381–9.
pubmed: 29483656
pmcid: 5918692
doi: 10.1038/s41588-018-0059-2
Peleg-Raibstein D, Yee BK, Feldon J, Hauser J. The amphetamine sensitization model of schizophrenia: relevance beyond psychotic symptoms? Psychopharmacol (Berl). 2009;206:603–21.
doi: 10.1007/s00213-009-1514-7
Underhill SM, Colt MS, Amara SG. Amphetamine stimulates endocytosis of the norepinephrine and neuronal glutamate transporters in cultured locus coeruleus neurons. Neurochem Res. 2020;45:1410–19.
pubmed: 31912366
pmcid: 7260265
doi: 10.1007/s11064-019-02939-6
Devoto P, Flore G, Pani L, Gessa GL. Evidence for co-release of noradrenaline and dopamine from noradrenergic neurons in the cerebral cortex. Mol Psychiatry. 2001;6:657–64.
pubmed: 11673793
doi: 10.1038/sj.mp.4000904
Kempadoo KA, Mosharov EV, Choi SJ, Sulzer D, Kandel ER. Dopamine release from the locus coeruleus to the dorsal hippocampus promotes spatial learning and memory. Proc Natl Acad Sci USA. 2016;113:14835–40.
pubmed: 27930324
pmcid: 5187750
doi: 10.1073/pnas.1616515114