Abstract
Therapeutic agents and drugs of abuse regulate the extracellular signal-regulated kinase (ERK) cascade signaling in the medium-sized spiny neurons (MSNs) of the striatum. However, whether this regulation is associated with specific cortical and thalamic inputs has never been studied. We used Drd2-EGFP BAC-transgenic mice to undertake a topographical and cell-type specific analysis of ERK phosphorylation and two of its downstream targets histone H3 and ribosomal protein S6 (rS6) in the dorsal striatum following injection of SKF81297 (D1R-like agonist), quinpirole (D2R-like agonist) or apomorphine (non selective DA receptor agonist). In striatal areas receiving inputs from the cingulate/prelimbic, visual and auditory cortex, SKF81297 treatment increased phosphorylation of ERK, histone H3 and rS6 selectively in EGFP-negative MSNs of Drd2-EGFP mice. In contrast, no regulation was found in striatal region predominantly targeted by the sensorimotor and motor cortex. Apomorphine slightly enhanced ERK and rS6, but not histone H3 phosphorylation. This regulation occurred exclusively in EGFP-negative neurons mostly in striatal sectors receiving connections from the insular, visual and auditory cortex. Quinpirole administration inhibited basal ERK activation but did not change histone H3 and rS6 phosphorylation throughout the rostrocaudal axis of the dorsal striatum. This anatomo-functional study indicates that D1R and D2R agonists produce a unique topography and cell-type specific regulation of the ERK cascade signaling in the mouse striatum, and that those patterns are closely associated with particular cortical and thalamic inputs. This work evidences the need of a precise identification of the striatal areas under study to further understand striatal plasticity.
Similar content being viewed by others
Abbreviations
- A:
-
Auditory cortex
- AI:
-
Agranular insular cortex
- Cg:
-
Cingulate cortex
- CL:
-
Centrolateral nucleus
- D1R:
-
Dopamine 1 receptor
- D2R:
-
Dopamine 2 receptor
- EGFP:
-
Enhanced green fluorescent protein
- ERK:
-
Extracellular signal-regulated kinase
- H3:
-
Histone H3
- IL:
-
Infralimbic cortex
- IMD:
-
Intermediodorsal nucleus
- LO:
-
Lateral orbital cortex
- M1/M2:
-
Motor cortex
- MGm:
-
Medial geniculate nucleus
- MSNs:
-
Medium-sized spiny neurons
- PC:
-
Paracentral nucleus
- PFdl:
-
Dorsolateral parafascicular nucleus
- PFvl:
-
Ventral lateral parafascicular nucleus
- PFm:
-
Medial parafascicular nucleus
- PIL:
-
Posterior intralaminar nucleus
- PL:
-
Prelimbic cortex
- PV:
-
Paraventricular nucleus
- rS6:
-
Ribosomal protein S6
- S:
-
Somatosensory cortex
- V:
-
Visual cortex
References
Alcantara AA, Chen V, Herring BE, Mendenhall JM, Berlanga ML (2003) Localization of dopamine D2 receptors on cholinergic interneurons of the dorsal striatum and nucleus accumbens of the rat. Brain Res 986:22–29
Alexander GE, Crutcher MD (1990) Functional architecture of basal ganglia circuits: neural substrates of parallel processing. Trends Neurosci 13:266–271
Arnauld E, Jeantet Y, Arsaut J, Demotes-Mainard J (1996) Involvement of the caudal striatum in auditory processing: c-fos response to cortical application of picrotoxin and to auditory stimulation. Brain Res Mol Brain Res 41:27–35
Bagetta V, Picconi B, Marinucci S, Sgobio C, Pendolino V, Ghiglieri V, Fusco FR, Giampa C, Calabresi P (2011) Dopamine-dependent long-term depression is expressed in striatal spiny neurons of both direct and indirect pathways: implications for Parkinson’s disease. J Neurosci 31:12513–12522
Beckstead RM (1988) Association of dopamine D1 and D2 receptors with specific cellular elements in the basal ganglia of the cat: the uneven topography of dopamine receptors in the striatum is determined by intrinsic striatal cells, not nigrostriatal axons. Neuroscience 27:851–863
Beckstead RM, Kersey KS (1985) Immunohistochemical demonstration of differential substance P-, met-enkephalin-, and glutamic-acid-decarboxylase-containing cell body and axon distributions in the corpus striatum of the cat. J Comp Neurol 232:481–498
Berendse HW, Galis-de Graaf Y, Groenewegen HJ (1992) Topographical organization and relationship with ventral striatal compartments of prefrontal corticostriatal projections in the rat. J Comp Neurol 316:314–347
Bertran-Gonzalez J, Bosch C, Maroteaux M, Matamales M, Herve D, Valjent E, Girault JA (2008) Opposing patterns of signaling activation in dopamine D1 and D2 receptor-expressing striatal neurons in response to cocaine and haloperidol. J Neurosci 28:5671–5685
Bertran-Gonzalez J, Hervé D, Girault JA, Valjent E (2010) What is the degree of segregation between striatonigral and striatopallidal projections? Front Neuroanat 4. pii:136
Bertran-Gonzalez J, Hakansson K, Borgkvist A et al (2009) Histone H3 phosphorylation is under the opposite tonic control of dopamine D2 and adenosine A2A receptors in striatopallidal neurons. Neuropsychopharmacology 34:1710–1720
Bolam JP, Hanley JJ, Booth PA, Bevan MD (2000) Synaptic organisation of the basal ganglia. J Anat 196(Pt 4):527–542
Brami-Cherrier K, Roze E, Girault JA, Betuing S, Caboche J (2009) Role of the ERK/MSK1 signalling pathway in chromatin remodelling and brain responses to drugs of abuse. J Neurochem 108:1323–1335
Brami-Cherrier K, Valjent E, Garcia M, Pages C, Hipskind RA, Caboche J (2002) Dopamine induces a PI3-kinase-independent activation of Akt in striatal neurons: a new route to cAMP response element-binding protein phosphorylation. J Neurosci 22:8911–8921
Brami-Cherrier K, Valjent E, Herve D, Darragh J, Corvol JC, Pages C, Arthur SJ, Girault JA, Caboche J (2005) Parsing molecular and behavioral effects of cocaine in mitogen- and stress-activated protein kinase-1-deficient mice. J Neurosci 25:11444–11454
Centonze D, Usiello A, Gubellini P, Pisani A, Borrelli E, Bernardi G, Calabresi P (2002) Dopamine D2 receptor-mediated inhibition of dopaminergic neurons in mice lacking D2L receptors. Neuropsychopharmacology 27:723–726
Chesselet MF, Graybiel AM (1983) Met-enkephalin-like and dynorphin-like immunoreactivities of the basal ganglia of the cat. Life Sci 33(Suppl 1):37–40
Choe ES, Wang JQ (2001) Group I metabotropic glutamate receptors control phosphorylation of CREB, Elk-1 and ERK via a CaMKII-dependent pathway in rat striatum. Neurosci Lett 313:129–132
Corvol JC, Valjent E, Pascoli V, Robin A, Stipanovich A, Luedtke RR, Belluscio L, Girault JA, Herve D (2007) Quantitative changes in Galphaolf protein levels, but not D1 receptor, alter specifically acute responses to psychostimulants. Neuropsychopharmacology 32:1109–1121
Crittenden JR, Graybiel AM (2011) Basal Ganglia disorders associated with imbalances in the striatal striosome and matrix compartments. Front Neuroanat 5:59
Deniau JM, Thierry AM (1997) Anatomical segregation of information processing in the rat substantia nigra pars reticulata. Adv Neurol 74:83–96
Doig NM, Moss J, Bolam JP (2010) Cortical and thalamic innervation of direct and indirect pathway medium-sized spiny neurons in mouse striatum. J Neurosci 30:14610–14618
Doly S, Bertran-Gonzalez J, Callebert J et al (2009) Role of serotonin via 5-HT2B receptors in the reinforcing effects of MDMA in mice. PLoS One 4:e7952
Fink JS, Weaver DR, Rivkees SA, Peterfreund RA, Pollack AE, Adler EM, Reppert SM (1992) Molecular cloning of the rat A2 adenosine receptor: selective co-expression with D2 dopamine receptors in rat striatum. Brain Res Mol Brain Res 14:186–195
Franklin K, Paxinos G (2007) The mouse brain in stereotaxic coordinates, 3rd edn. Elsevier
Fujiyama F, Unzai T, Nakamura K, Nomura S, Kaneko T (2006) Difference in organization of cortistriatal and thalamostriatal synapses between patch and matrix compartments of rat neostriatum. Eur J Neurosci 24:2813–2824
Gangarossa G, Di Benedetto M, O’Sullivan GJ et al (2011) Convulsant doses of a dopamine D1 receptor agonist result in Erk-dependent increases in Zif268 and Arc/Arg3.1 expression in mouse dentate gyrus. PLoS One 6:e19415
Gerfen CR (1984) The neostriatal mosaic: compartmentalization of corticostriatal input and striatonigral output systems. Nature 311:461–464
Gerfen CR (1992) The neostriatal mosaic: multiple levels of compartmental organization. Trends Neurosci 15:133–139
Gerfen CR, Baimbridge KG, Miller JJ (1985) The neostriatal mosaic: compartmental distribution of calcium-binding protein and parvalbumin in the basal ganglia of the rat and monkey. Proc Natl Acad Sci USA 82:8780–8784
Gerfen CR, Engber TM, Mahan LC, Susel Z, Chase TN, Monsma FJ Jr, Sibley DR (1990) D1 and D2 dopamine receptor-regulated gene expression of striatonigral and striatopallidal neurons. Science 250:1429–1432
Gerfen CR, Miyachi S, Paletzki R, Brown P (2002) D1 dopamine receptor supersensitivity in the dopamine-depleted striatum results from a switch in the regulation of ERK1/2/MAP kinase. J Neurosci 22:5042–5054
Gerfen CR, Paletzki R, Worley P (2008) Differences between dorsal and ventral striatum in Drd1a dopamine receptor coupling of dopamine- and cAMP-regulated phosphoprotein-32 to activation of extracellular signal-regulated kinase. J Neurosci 28:7113–7120
Gerfen CR, Surmeier DJ (2011) Modulation of striatal projection systems by dopamine. Annu Rev Neurosci 34:441–466
Girault JA, Valjent E, Caboche J, Herve D (2007) ERK2: a logical AND gate critical for drug-induced plasticity? Curr Opin Pharmacol 7:77–85
Goldman PS, Nauta WJ (1977) An intricately patterned prefronto-caudate projection in the rhesus monkey. J Comp Neurol 72:369–386
Gong S, Zheng C, Doughty ML et al (2003) A gene expression atlas of the central nervous system based on bacterial artificial chromosomes. Nature 425:917–925
Graybiel AM (2004) Network-level neuroplasticity in cortico-basal ganglia pathways. Parkinsonism Relat Disord 10:293–296
Haber SN (2003) The primate basal ganglia: parallel and integrative networks. J Chem Neuroanat 26:317–330
Haber SN, Calzavara R (2009) The cortico-basal ganglia integrative network: the role of the thalamus. Brain Res Bull 78:69–74
Jiao H, Zhang L, Gao F, Lou D, Zhang J, Xu M (2007) Dopamine D(1) and D(3) receptors oppositely regulate NMDA- and cocaine-induced MAPK signaling via NMDA receptor phosphorylation. J Neurochem 103:840–848
Kawaguchi Y, Wilson CJ, Augood SJ, Emson PC (1995) Striatal interneurones: chemical, physiological and morphological characterization. Trends Neurosci 18:527–535
Kelleher RJ 3rd, Govindarajan A, Jung HY, Kang H, Tonegawa S (2004a) Translational control by MAPK signaling in long-term synaptic plasticity and memory. Cell 116:467–479
Kelleher RJ 3rd, Govindarajan A, Tonegawa S (2004b) Translational regulatory mechanisms in persistent forms of synaptic plasticity. Neuron 44:59–73
Kim DS, Palmiter RD, Cummins A, Gerfen CR (2006) Reversal of supersensitive striatal dopamine D1 receptor signaling and extracellular signal-regulated kinase activity in dopamine-deficient mice. Neuroscience 137:1381–1388
Kramer PF, Christensen CH, Hazelwood LA, Dobi A, Bock R, Sibley DR, Mateo Y, Alvarez VA (2011) Dopamine D2 receptor overexpression alters behavior and physiology in Drd2-EGFP mice. J Neurosci 31:126–132
Lanciego JL, Gonzalo N, Castle M, Sanchez-Escobar C, Aymerich MS, Obeso JA (2004) Thalamic innervation of striatal and subthalamic neurons projecting to the rat entopeduncular nucleaus. Eur J Neurosci 19:1267–1277
Le Moine C, Tison F, Bloch B (1990) D2 dopamine receptor gene expression by cholinergic neurons in the rat striatum. Neurosci Lett 117:248–252
Mahadevan LC, Willis AC, Barratt MJ (1991) Rapid histone H3 phosphorylation in response to growth factors, phorbol esters, okadaic acid, and protein synthesis inhibitors. Cell 65:775–783
Malach R, Graybiel AM (1986) Mosaic architecture of the somatic sensory-recipient sector of the cat’s striatum. J Neurosci 6:3436–3458
Matamales M, Bertran-Gonzalez J, Salomon L, Degos B, Deniau JM, Valjent E, Hervé D, Girault JA (2009) Striatal medium-sized spiny neurons: identification by nuclear staining and study of neuronal subpopulations in BAc transgenic mice. pLoS One 4(3):e4770
Mercuri NB, Saiardi A, Bonci A, Picetti R, Calabresi P, Bernardi G, Borrelli E (1997) Loss of autoreceptor function in dopaminergic neurons from dopamine D2 receptor deficient mice. Neuroscience 79:323–327
Nicola SM (2007) The nucleus accumbens as part of a basal ganglia action selection circuit. Psychopharmacology (Berl) 191:521–550
Parent A, Bouchard C, Smith Y (1984) The striatopallidal and striatonigral projections: two distinct fiber systems in primate. Brain Res 303:385–390
Pascoli V, Besnard A, Herve D, Pages C, Heck N, Girault JA, Caboche J, Vanhoutte P (2011) Cyclic adenosine monophosphate-independent tyrosine phosphorylation of NR2B mediates cocaine-induced extracellular signal-regulated kinase activation. Biol Psychiatry 69:218–227
Pavon N, Martin AB, Mendialdua A, Moratalla R (2006) ERK phosphorylation and FosB expression are associated with l-DOPA-induced dyskinesia in hemiparkinsonian mice. Biol Psychiatry 59:64–74
Penney JB Jr, Young AB (1983) Speculations on the functional anatomy of basal ganglia disorders. Annu Rev Neurosci 6:73–94
Pisani A, Bonsi P, Centonze D, Calabresi P, Bernardi G (2000) Activation of D2-like dopamine receptors reduces synaptic inputs to striatal cholinergic interneurons. J Neurosci 20:RC69
Ruvinsky I, Meyuhas O (2006) Ribosomal protein S6 phosphorylation: from protein synthesis to cell size. Trends Biochem Sci 31:342–348
Salzmann J, Marie-Claire C, Le Guen S, Roques BP, Noble F (2003) Importance of ERK activation in behavioral and biochemical effects induced by MDMA in mice. Br J Pharmacol 140:831–838
Santini E, Alcacer C, Cacciatore S, Heiman M, Herve D, Greengard P, Girault JA, Valjent E, Fisone G (2009) l-DOPA activates ERK signaling and phosphorylates histone H3 in the striatonigral medium spiny neurons of hemiparkinsonian mice. J Neurochem 108:621–633
Schiffmann SN, Jacobs O, Vanderhaeghen JJ (1991) Striatal restricted adenosine A2 receptor (RDC8) is expressed by enkephalin but not by substance P neurons: an in situ hybridization histochemistry study. J Neurochem 57:1062–1067
Shiflett MW, Balleine BW (2011) Contributions of ERK signaling in the striatum to instrumental learning and performance. Behav Brain Res 218:240–247
Smith Y, Kieval JZ (2000) Anatomy of the dopamine system in the basal ganglia. Trends Neurosci 23:S28–S33
Smith Y, Raju DV, Pare JF, Sidibe M (2004) The thalamostriatal system: a highly specific network of the basal ganglia circuitry. Trends Neurosci 27:520–527
Surmeier DJ, Song WJ, Yan Z (1996) Coordinated expression of dopamine receptors in neostriatal medium spiny neurons. J Neurosci 16:6579–6591
Tepper JM, Bolam JP (2004) Functional diversity and specificity of neostriatal interneurons. Curr Opin Neurobiol 14:685–692
Thomson S, Clayton AL, Hazzalin CA, Rose S, Barratt MJ, Mahadevan LC (1999) The nucleosomal response associated with immediate-early gene induction is mediated via alternative MAP kinase cascades: MSK1 as a potential histone H3/HMG-14 kinase. EMBO J 18:4779–4793
Valjent E, Bertran-Gonzalez J, Aubier B, Greengard P, Herve D, Girault JA (2010) Mechanisms of locomotor sensitization to drugs of abuse in a two-injection protocol. Neuropsychopharmacology 35:401–415
Valjent E, Bertran-Gonzalez J, Herve D, Fisone G, Girault JA (2009) Looking BAC at striatal signaling: cell-specific analysis in new transgenic mice. Trends Neurosci 32:538–547
Valjent E, Corvol JC, Pages C, Besson MJ, Maldonado R, Caboche J (2000) Involvement of the extracellular signal-regulated kinase cascade for cocaine-rewarding properties. J Neurosci 20:8701–8709
Valjent E, Pages C, Herve D, Girault JA, Caboche J (2004) Addictive and non-addictive drugs induce distinct and specific patterns of ERK activation in mouse brain. Eur J Neurosci 19:1826–1836
Valjent E, Pascoli V, Svenningsson P et al (2005) Regulation of a protein phosphatase cascade allows convergent dopamine and glutamate signals to activate ERK in the striatum. Proc Natl Acad Sci USA 102:491–496
Westin JE, Vercammen L, Strome EM, Konradi C, Cenci MA (2007) Spatiotemporal pattern of striatal ERK1/2 phosphorylation in a rat model of l-DOPA-induced dyskinesia and the role of dopamine D1 receptors. Biol Psychiatry 62:800–810
Willuhn I, Sun W, Steiner H (2003) Topography of cocaine-induced gene regulation in the rat striatum: relationship to cortical inputs and role of behavioural context. Eur J Neurosci 17:1053–1066
Yan Z, Feng J, Fienberg AA, Greengard P (1999) D(2) dopamine receptors induce mitogen-activated protein kinase and cAMP response element-binding protein phosphorylation in neurons. Proc Natl Acad Sci USA 96:11607–11612
Yano M, Steiner H (2005a) Methylphenidate (Ritalin) induces Homer 1a and zif 268 expression in specific corticostriatal circuits. Neuroscience 132:855–865
Yano M, Steiner H (2005b) Topography of methylphenidate (ritalin)-induced gene regulation in the striatum: differential effects on c-fos, substance P and opioid peptides. Neuropsychopharmacology 30:901–915
Acknowledgments
This work was supported by Inserm and grants from ATIP-Avenir (Inserm), Sanofi-Aventis R&D and from the Agence Nationale de la Recherche (ANR-2010-JCJC-1412) to Emmanuel Valjent. Giuseppe Gangarossa was supported by a Short-Term fellowship (Ambassade de France). We thank Dr Dimitri De Bundel for comments on the manuscript. We are grateful to Laurent Fagni (Institut de Génomique Fonctionnelle) for providing the transgenic mice used in this study. We thank Fredéric Gallardo and Florence Arnal for animal care, breeding and genotyping.
Conflict of interest
The authors declare that they have no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Below is the link to the electronic supplementary material.
429_2012_405_MOESM2_ESM.tif
Supplemental Figure 1. Identification of EGFP-expressing striatal neurons in Drd2-EGFP mice. Parvalbumin immunoreactivity (cyan) was detected together with EGFP (green) and DARPP-32 (red) immunoreactivity in the dorsal striatum of Drd2-EGFP mice in a triple fluorescence analysis. Arrowheads (yellow) indicate the position of parvalbumin-positive GABAergic interneurons. Arrows (yellow) indicate the position of cholinergic interneurons, which can be detected in Drd2-EGFP mice (Bertran-Gonzalez et al. 2008; Matamales et al. 2009). Scale bar 30 µm (TIFF 716 kb)
429_2012_405_MOESM3_ESM.tif
Supplemental Figure 2. SKF81297 induces ERK activation in DARPP-32-expressing neurons. P-ERK immunoreactivity (red) was detected together with DARPP-32 (blue) and EGFP (green) immunoreactivity in the striatal sector receiving afferents from the cingulate cortex of Drd2-EGFP mice treated with vehicle or SKF81297 (5 mg/kg) in a triple fluorescence analysis. Arrowheads (yellow) illustrate P-ERK/DARPP-32-positive cells and the complete lack of co-localization with EGFP-expressing neurons revealing that SKF81297-induced ERK activation is restricted in D1R-containing MSNs. Scale bar: 50 µm (TIFF 893 kb)
Rights and permissions
About this article
Cite this article
Gangarossa, G., Perroy, J. & Valjent, E. Combinatorial topography and cell-type specific regulation of the ERK pathway by dopaminergic agonists in the mouse striatum. Brain Struct Funct 218, 405–419 (2013). https://doi.org/10.1007/s00429-012-0405-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00429-012-0405-6