Structural organization, GABAergic and tyrosine hydroxylase expression in the striatum and globus pallidus of the South American plains vizcacha, Lagostomus maximus (Rodentia, Caviomorpha)

  • Alejandro Raúl Schmidt
  • Pablo Ignacio Felipe Inserra
  • Santiago Andrés Cortasa
  • Santiago Elías Charif
  • Sofía Proietto
  • María Clara Corso
  • Federico Villarreal
  • Julia Halperin
  • César Fabián Loidl
  • Alfredo Daniel Vitullo
  • Verónica Berta DorfmanEmail author
Original Paper


The striatum is an essential component of the basal ganglia that regulatessensory processing, motor, cognition, and behavior. Depending on the species, the striatum shows a unique structure called caudate–putamen as in mice, or its separation into two regions called caudate and lenticular nuclei, the latter formed by putamen and globus pallidus areas, as in primates. These structures have two compartments, striosome and matrix. We investigated the structural organization, GABAergic and tyrosine hydroxylase (TH) expression in the striatum and globus pallidus of the South American plains vizcacha, Lagostomus maximus. Its striatum showed regionalization arising from the presence of an internal capsule, and a similar organization to a striosome–matrix compartmentalization. GABAergic neurons in the matrix of caudate exhibited parvalbumin, calretinin, calbindin, GAD65, and NADPH-d-immunoreactivity. These were also expressed in cells of the putamen with the exception of calretinin showing neurofibers localization. Globus pallidus showed parvalbumin- and GAD65-immunoreactive cells, and calretinin- and calbindin-immunoreactive neuropil, plus GABA-A-immunoreactive neurofibers. NADPH-d-, GAD65- and GABA-A-immunoreactive neurons were larger than parvalbumin-, calretinin-, and calbindin-immunoreactive cells, whereas calbindin-immunoreactive cells were the most abundant. In addition, TH-immunoreactive neuropil was observed in the matrix of the striatum. A significant larger TH-immunoreactive area and neuron number was found in females compared to males. The presence of an internal capsule suggests an adaptive advantage concerning motor and cognitive abilities favoring reaction time in response to predators. In an anatomy-evolutive perspective, the striatum of vizcacha seems to be closer to that of humans than to that of laboratory traditional models such as mouse.


Striatum GABA Tyrosine hydroxylase Sexual dimorphism Vizcacha 



We are especially grateful to the Ministerio de AsuntosAgrarios, Dirección de Flora y Fauna, Buenos Aires Province Government for enabling animal capture, to the personnel of ECAS for their invaluable help in trapping and handling the animals, to MV. Sergio Ferraris and MV. Fernando Lange and their veterinarian staff for their essential help on vizcachas handling and anesthetizing, to Ms. Sol ClausiSchettini for her excellent technical assistance in tissue processing, and Mr. Santiago Cicculli for his microscopy technical assistance.This work was funded by theNational Scientific and Technical Research Council(CONICET): PIP No. 110/14, National Scientific and Technical Ministry (MINCyT): PICT-1281/2014, and by FundaciónCientífica Felipe Fiorellino, Universidad Maimónides, Argentina.

Compliance with ethical standards

Conflict of interest

The authors declare that there is no conflict of interest.


  1. Arvidsson E, Viereckel T, Mikulovic S, Wallen-Mackenzie A (2014) Age- and sex-dependence of dopamine release and capacity for recovery identified in the dorsal striatum of C57/BI6J mice. PLoS ONE 9(6):e99592CrossRefGoogle Scholar
  2. Bae EJ, Chen BH, Shin BN, Cho JH, Kim IH, Park JH, Lee JC, Tae HJ, Choi SY, Kim JD, Lee YL, Won MH, Ahn JH (2015) Comparison of immunoreactivities of calbindin-D28k, calretinin and parvalbumin in the striatumbetween young, adult and aged mice, rats and gerbils. Neurochem Res 40(4):864–872CrossRefGoogle Scholar
  3. Becker JB (1999) Gender differences in dopaminergic function in striatum and nucleus accumbens. Pharmacol Biochem Behav 64:803–812CrossRefGoogle Scholar
  4. Becker JB, Snyder PJ, Miller MM, Westgate SA, Jenuwine MJ (1987) The influence of estrous cycle and intrastriatal estradiol on sensorimotor performance in the female rat. Pharmacol Biochem Behav 27:53–59CrossRefGoogle Scholar
  5. Bee de Speroni N, Pellegrini de Gastaldo A (1988) Encefalización y composición cerebral en tres roedores sudamericanos (Dolichotis patagonum, Lagostomus maximus y Calomys musculinus). Physis 46(111):31–39Google Scholar
  6. Bradford MM (1976) Rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254CrossRefGoogle Scholar
  7. Branch LC (1993a) Social organization and mating system of the plains viscacha (Lagostomus maximus). J Zool (London) 229:473–491CrossRefGoogle Scholar
  8. Branch LC (1993b) Seasonal patterns of activity and body mass in plains vizcacha, Lagostomus maximus (family Chinchillidae). Can J Zool 71:1041–1045CrossRefGoogle Scholar
  9. Branch LC (1995) Observations of predation by pumas and Geoffroy's cats on the plains vizcacha in semiarid scrub of central Argentina. Mammalia 59:152–156Google Scholar
  10. Carpenter MB (1994) Neuroanatomía: fundamentos 4th edition. Medica Panamericana. 448 pag. ISBN: 9788479031732.Google Scholar
  11. Charif SE, Inserra PIF, Schmidt AR, Di Giorgio NP, Cortasa SA, Gonzalez CR, Lux-Lantos V, Halperin J, Vitullo AD, Dorfman VB (2017) Local production of neurostradiol affects gonadotropin-releasing hormone (GnRH) secretion at mid-gestation in Lagostomus maximus (Rodentia, Caviomorpha). Physiol Rep 5(19):e13439CrossRefGoogle Scholar
  12. Charif SE, Inserra PIF, Di Giorgio NP, Schmidt AR, Lux-Lantos V, Vitullo AD, Dorfman VB (2016) Sequence analysis, tissue distribution and molecular physiology of the GnRH preprogonadotrophin in the South American plains vizcacha (Lagostomus maximus). Gen Comp Endocrinol 232:174–184CrossRefGoogle Scholar
  13. Churakov G, Sadasivuni MK, Rosenbloom KR, Huchon D, Brosius J, Schmitz J (2010) Rodent evolution: back to the root. Mol Biol Evol 27:1315–1326CrossRefGoogle Scholar
  14. Contreras JR (1981) El tunduque: Un modelo de ajuste adaptativo. Serie Científica 22–25.Google Scholar
  15. Cossette M, Lecomte F, Parent A (2005) Morphology and distribution of dopaminergic neurons intrinsic to the human striatum. J Chem Neuroanat 29:1–11CrossRefGoogle Scholar
  16. Daubner SC, Le T, Wang S (2011) Tyrosine hydroxylase and regulation of dopamine synthesis. Arch Biochem Biophys 508(1):1–12CrossRefGoogle Scholar
  17. Daw ND, Niv Y, Dayan P (2005) Uncertainty-based competition between prefrontal and dorsolateral striatal systems for behavioral control. Nat Neurosci 8:1704–1711CrossRefGoogle Scholar
  18. Dayan P, Niv Y, Seymour B, Daw ND (2006) The misbehavior of value and the discipline of the will. Neural Netw 19:1153–1160CrossRefGoogle Scholar
  19. De las Heras S, Hontanilla B, Mengual E, Giménez-Amaya JM (1994) Immunohistochemical distribution of calbindin D-28k and parvalbumin in the head of the caudate nucleus and substantia nigra of the cat. J Morphol 221(3):291–307CrossRefGoogle Scholar
  20. DeLong M, Alexander GE, Georgopoulos AP, Crutcher MD, Mitchell SJ, Richardson RT (1984) Role of basal ganglia in limb movements. Hum Neurobiol 2:235–244Google Scholar
  21. DeLong MR, Georgopoulos AP (1981) Motor functions of the basal ganglia. Handb Physiol 3:1017–1061Google Scholar
  22. Dorfman VB, Fraunhoffer N, Inserra PIF, Loidl CF, Vitullo AD (2011) Histological characterization of gonadotropin-releasing hormone (GnRH) in the hypothalamus of the South American plains vizcacha (Lagostomus maximus). J Mol Histol 42:311–321CrossRefGoogle Scholar
  23. Dorfman VB, Saucedo L, Di Giorgio NP, Inserra PIF, Fraunhoffer N, Leopardo NP, Halperin J, Lux-Lantos V, Vitullo AD (2013) Variation in progesterone receptors and GnRH expression in the hypothalamus of the pregnant South American plains vizcacha, Lagostomus maximus (Mammalia, Rodentia). Biol Reprod 89(5):115–125CrossRefGoogle Scholar
  24. Dubach M, Schmidt R, Kunkel D, Bowden DM, Martin R, German DC (1987) Primate neostriatal neurons containing tyrosine hydroxylase: immunohisto-chemical evidence. Neurosci Lett 75:205–210CrossRefGoogle Scholar
  25. Fujiyama F, Unzai T, Nakamura K, Nomura S, Kaneko T (2006) Difference in organization of corticostriatal and thalamostriatal synapsesbetween patch and matrix compartments of rat neostriatum. Eur J Neurosci 24:2813–2824CrossRefGoogle Scholar
  26. Gerfen CR (1984) The neostriatal mosaic: compartmentalization of corticostriatal input and striatonigral output systems. Nature 311:461–464. CrossRefGoogle Scholar
  27. Gerfen CR, Wilson CJ (1996) The Basal Ganglia. In: Hokfelt T, Swanson LW (eds) Handbook of Chemical Neuroanatomy. Elsevier, Amsterdam, pp 365–462Google Scholar
  28. Gillies A, Willshaw D, Li Z (2002) Subthalamic-pallidal interactions are critical in determining normal and abnormal functioning of the basal ganglia. Proc Biol Sci 269(1491):545–551CrossRefGoogle Scholar
  29. Gonzalez CR, Muscarsel Isla ML, Fraunhoffer NA, Leopardo NP, Vitullo AD (2012a) Germ cell differentiation and proliferation in the developing testis of the South American plains viscacha, Lagostomus maximus (Mammalia, Rodentia). Zygote 20(3):219–227CrossRefGoogle Scholar
  30. Gonzalez CR, Muscarsel Isla ML, Leopardo NP, Willis MA, Dorfman VB, Vitullo AD (2012b) Expression of androgen receptor, estrogen receptors alpha and beta and aromatase in the fetal, perinatal, prepubertal and adult testes of the South American plains vizcacha, Lagostomus maximus (Mammalia, Rodentia). J Reprod Dev 58(6):629–635CrossRefGoogle Scholar
  31. Gonzalez CR, Muscarsel Isla ML, Vitullo AD (2018) The balance between apoptosis and autophagy regulates testis regression and recrudescence in the seasonal-breeding South American plains vizcacha, Lagostomus maximus. PLoS ONE 13(1):e0191126CrossRefGoogle Scholar
  32. Graybiel AM (1983) Compartmental organization of the mammalian striatum. Prog Brain Res 58:247–256CrossRefGoogle Scholar
  33. Graybiel AM (1990) Neurotransmitters and neuromodulators in the basal ganglia. Trends Neurosci 13:244–254. CrossRefGoogle Scholar
  34. Graybiel AM (2008) Habits, rituals, and the evaluative brain. Annu Rev Neurosci 31:359–387. CrossRefGoogle Scholar
  35. Graybiel AM, Ragsdale CW (1978) Histochemically distinct compartments in the striatum of human, monkey and cat demonstrated by acetylthiocholinesterase staining. Proc Natl Acad Sci 75(11):5723–5726CrossRefGoogle Scholar
  36. Halperin J, Dorfman VB, Fraunhoffer N, Vitullo AD (2013) Estradiol, progesterone and prolactin modulate mammary gland morphogenesis in adult female plains vizcacha (Lagostomus maximus). J Mol Histol 44(3):299–310CrossRefGoogle Scholar
  37. Herkenham M, Pert CB (1981) Mosaic distribution of opiate receptors, parafascicular projections and acetylcholinesterase in rat striatum. Nature 291:415–418. CrossRefGoogle Scholar
  38. Holt DJ, Graybiel AM, Saper CB (1997) Neurochemical architecture of the human striatum. J Comp Neurol 384:1–25CrossRefGoogle Scholar
  39. Inserra PIF, Charif SE, Di Giorgio NP, Saucedo L, Schmidt AR, Fraunhoffer N, Halperin J, Gariboldi MC, Leopardo NP, Lux-Lantos V, Gonzalez CR, Vitullo AD, Dorfman VB (2017) ERα and GnRH co-localize in the hypothalamic neurons of the South American plains vizcacha, Lagostomus maximus (Rodentia, Caviomorpha). J Mol Histol 48(3):259–273CrossRefGoogle Scholar
  40. Jackson JE (1986) Determinación de edad en la vizcacha (Lagostomus maximus) en base al peso del cristalino. Vida Silvestre Neotropical 1:41–44Google Scholar
  41. Jackson JE, Lyn C, Villarreal D (1996) Lagostomus maximus mammalian. Species 543:1–6Google Scholar
  42. Jensen F, Willis MA, Albamonte MS, Espinosa MB, Vitullo AD (2006) Naturally suppressed apoptosis prevents follicular atresia and oocyte reserve decline in the adult ovary of Lagostomus maximus (Rodentia, Caviomorpha). Reproduction 132:301–308CrossRefGoogle Scholar
  43. Kawaguchi Y, Wilson CJ, Augood SJ, Emson PC (1995) Striatal interneurones: chemical, physiological and morphological characterization. Trends Neurosci 18(12):527–535CrossRefGoogle Scholar
  44. Kelava I, Lewitus E, Huttner WB (2013) The secondary loss of gyrencephaly as an example of evolutionary phenotypical reversal. Front Neuroanat 7:16CrossRefGoogle Scholar
  45. Kita H, Jaeger D (2016) Organization of the Globus Pallidus. Handb Behav Neurosci 24:259–276. CrossRefGoogle Scholar
  46. Kubota Y, Inagaki S, Kito S (1986) Innervation of substance P neurons by catecholaminergic terminals in the neostriatum. Brain Res 375:163–167. CrossRefGoogle Scholar
  47. Kubota Y, Kawaguchi Y (1993) Spatial distributions of chemically identified intrinsic neurons in relations to patch and matrix compartments of rat neostriatum. J Comp Neurol 332:499–513. CrossRefGoogle Scholar
  48. Klüver H, Barrera E (1953) A method for the combined staining of cells and fibers in the nervous system. J Nueropathol Exp Neurol 12:400–403CrossRefGoogle Scholar
  49. Kreitzer AC, Malenka RC (2008) Striatal plasticity and basal ganglia circuit function. Neuron 60(4):543–554CrossRefGoogle Scholar
  50. Lavoie B, Parent A (1990) Immunohistochemical study of the serotonergic innervation of the basal ganglia in the squirrel monkey. J Comp Neurol 1:1. CrossRefGoogle Scholar
  51. Leranth C, Roth RH, Elsworth JD, Naftolin F, Horvath TL, Redmond DE Jr (2000) Estrogen is essential for maintaining nigrostriatal dopamine neurons in primates: implications for Parkinson’s Disease and memory. J Neurosci 20(23):8604–8609CrossRefGoogle Scholar
  52. Liljeholm M, O’Doherty JP (2012) Contributions of the striatum to learning, motivation and performance: an associative account. Trends Cogn Sci 16(9):467–475CrossRefGoogle Scholar
  53. Llanos AC, Crespo JA (1952) Ecología de la vizcacha (Lagostomus maximus maximus Blainv.) en el nordeste de la Provincia de Entre Ríos. Revista de Investigaciones Agrícolas 6:289–378Google Scholar
  54. Luparello TJ, Stein M, Park CD (1964) A stereotaxic atlas of the hypothalamus of the guinea pig. J Comp Neurol 122:201–217CrossRefGoogle Scholar
  55. McDermott JL, Liu B, Dluzen DE (1994) Sex differences and effects of estrogen on dopamine and DOPAC release from the striatum of male and female CD-1 mice. Exp Neurol 125:306–311CrossRefGoogle Scholar
  56. Mensah P, Deadwyler S (1974) The caudate nucleus of the rat: cell types and the demonstration of a commissural system. J Anat 117:281–293Google Scholar
  57. Meredith GE, Farrell T, Kellaghan P, Tan Y, Zahm DS, Totterdell S (1999) Immunocytochemical characterization of catecholaminergic neurons in the rat striatum followingdopamine-depleting lesions. Eur J Neurosci 10:3585–3596CrossRefGoogle Scholar
  58. Micheli FE and Luquin-Piudo ME (2012) Functional organization of basal ganglia. Abnormal movements. Ed: Medica Panamericana, Chapter 2.Google Scholar
  59. Middleton FA, Strick PL (1994) Anatomical evidence for cerebellar and basal ganglia involvement in higher cognitive function. Science 226:452–461Google Scholar
  60. Nevo E (1979) Adaptive convergence and divergence of subterranean mammals. Annu Rev Ecol Evol Syst 10:269–308CrossRefGoogle Scholar
  61. National Research Council USA (2011) Guide for the care and use of laboratory enimals, 8th edn. The National Academies Press, WashingtonGoogle Scholar
  62. Orendain-Jaime EN, Ortega-Ibarra JM, López-Pérez SJ (2016) Evidence of sexual dimorphism in D1 and D2 dopaminergic receptors expression in frontal cortex and striatum of young rats. Neurochem Int 100:62–66CrossRefGoogle Scholar
  63. Parent A, Hazrati LN (1995) Functional anatomy of the basal ganglia. I. The cortico-basal ganglia-thalamo-cortical loop. Brain Res Rev 20:91–127CrossRefGoogle Scholar
  64. Paxinos G, Watson C (2013) The rat brain in stereotaxic coordinates. AP press, AmsterdamGoogle Scholar
  65. Paxinos G, Franklin KBJ (2004) The mouse brain in stereotaxic coordinates. Elsevier Academic Press, AmsterdamGoogle Scholar
  66. Rey-Funes M, Dorfman VB, Ibarra ME, Peña E, Contartese DE, Goldstein J, Acosta JM, Larráyoz I, Martínez-Murillo R, Martínez A, Loidl CF (2013) Hypothermia prevents gliosis and angiogenesis development in an experimental model of ischemic proliferative retinopathy. Invest Ophthalmol Vis Sci 54(4):2836–2846CrossRefGoogle Scholar
  67. Rey-Funes M, Larráyoz I, Fernández J, Contartese D, Rolón F, Inserra PIF, Martínez-Murillo R, López-Costa J, Dorfman VB, Martínez A, Loidl CF (2016) Methylene blue prevents retinal damage in an experimental model of ischemic proliferative retinopathy. Am J Physiol Regul Integr Comp Physiol 310(11):R1011–1019CrossRefGoogle Scholar
  68. Rice MW, Roberts RC, Melendez-Ferro M, Perez-Costas E (2011) Neurochemical characterization of the tree shrew dorsal striatum. Front Neuroanat 5:1–16CrossRefGoogle Scholar
  69. Sandell JH, Graybiel AM, Chesselet MF (1986) A new enzyme marker for striatal compartmentalization: NADPH diaphorase activity in the caudate nucleus and putamen of the cat. J Comp Nneurol 243:326–334CrossRefGoogle Scholar
  70. Smith Y, Bevan MD, Shink E, Bolam JP (1998) Microcircuitry of the direct and indirect pathwaysof the basal ganglia. Neuroscience 86(2):353–387CrossRefGoogle Scholar
  71. Snell RS (2007) Neuroanatomía clínica 6 ed. Medica Panamericana, p 594Google Scholar
  72. Tindal JS (1965) The forebrain of the guinea pig in stereotaxic coordinates. J Comp Neurol 124:259–256CrossRefGoogle Scholar
  73. Vincent SR, Johansson O (1983) Striatal neurons containing both somatostatin and avian pancreatic polypeptide APPI-like immunoreactivities and NADPH diaphorase activity: a light and electron microscopic study. J Comp Neurol 217:264–270CrossRefGoogle Scholar
  74. Voloch CM, Vilela JF, Loss-Oliveira L, Schrago CG (2013) Phylogeny and chronology of the major lineages of New World hystricognath rodents: insights on the biogeography of the Eocene/Oligocene arrival of mammals in South America. BMC Res Notes 6:160CrossRefGoogle Scholar
  75. Walker QD, Rooney MB, Wightman RM, Kuhn CM (1999) Dopamine release and uptake are greater in female than male rat striatum as measured by fast cyclic voltammetry. Neuroscience 95(4):1061–1070CrossRefGoogle Scholar
  76. Wu Y, Parent A (2000) Striatal interneurons expressing calretinin, parvalbumin or NADPH-diaphorase: a comparative study in the rat, monkey and human. Brain Res 863(1–2):182–191CrossRefGoogle Scholar
  77. Xenias HS, Ibáñez-Sandoval O, Koós T, Tepper JM (2015) Are striatal tyrosine hydroxylase interneurons dopaminergic? J Neurosci 35(16):6584–6599CrossRefGoogle Scholar
  78. Xiao L, Becker JB (1994) Quantitative microdialysis determination of extracellular striatal dopamine concentrations in male and female rats: effects of estrous cycle and gonadectomy. Neurosci Lett 180:155–158CrossRefGoogle Scholar
  79. Yelnik J, Francois C, Percheron G, Tande D (1991) Morphological taxonomy of the neurons of the primate striatum. J Comp Neurol 313:273–294CrossRefGoogle Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Alejandro Raúl Schmidt
    • 1
    • 3
  • Pablo Ignacio Felipe Inserra
    • 1
    • 3
  • Santiago Andrés Cortasa
    • 1
    • 3
  • Santiago Elías Charif
    • 1
    • 3
  • Sofía Proietto
    • 1
    • 3
  • María Clara Corso
    • 1
    • 3
  • Federico Villarreal
    • 1
  • Julia Halperin
    • 1
    • 3
  • César Fabián Loidl
    • 2
  • Alfredo Daniel Vitullo
    • 1
    • 3
  • Verónica Berta Dorfman
    • 1
    • 3
    Email author
  1. 1.Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y Diagnóstico (CEBBAD)Universidad MaimónidesCiudad Autónoma de Buenos AiresArgentina
  2. 2.Laboratorio de Neuropatología Experimental, Instituto de Biología Celular Y Neurociencia (IBCN) “Prof. E. De Robertis”, Facultad de MedicinaUniversidad de Buenos Aires, CONICETCiudad Autónoma de Buenos AiresArgentina
  3. 3.Consejo Nacional de Investigaciones Científicas Y Técnicas (CONICET)Buenos AiresArgentina

Personalised recommendations