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Morphological Study of the Cortical and Thalamic Glutamatergic Synaptic Inputs of Striatal Parvalbumin Interneurons in Rats

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Abstract

Parvalbumin-immunoreactive (Parv+) interneurons is an important component of striatal GABAergic microcircuits, which receive excitatory inputs from the cortex and thalamus, and then target striatal projection neurons. The present study aimed to examine ultrastructural synaptic connection features of Parv+ neruons with cortical and thalamic input, and striatal projection neurons by using immuno-electron microscopy (immuno-EM) and immunofluorescence techniques. Our results showed that both Parv+ somas and dendrites received numerous asymmetric synaptic inputs, and Parv+ terminals formed symmetric synapses with Parv− somas, dendrites and spine bases. Most interestingly, spine bases targeted by Parv+ terminals simultaneously received excitatory inputs at their heads. Electrical stimulation of the motor cortex (M1) induced higher proportion of striatal Parv+ neurons express c-Jun than stimulation of the parafascicular nucleus (PFN), and indicated that cortical- and thalamic-inputs differentially modulate Parv+ neurons. Consistent with that, both Parv + soma and dendrites received more VGlut1+ than VGlut2+ terminals. However, the proportion of VGlut1+ terminal targeting onto Parv+ proximal and distal dendrites was not different, but VGlut2+ terminals tended to target Parv+ somas and proximal dendrites than distal dendrites. These functional and morphological results suggested excitatory cortical and thalamic glutamatergic inputs differently modulate Parv+ interneurons, which provided inhibition inputs onto striatal projection neurons. To maintain the balance between the cortex and thalamus onto Parv+ interneurons may be an important therapeutic target for neurological disorders.

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References

  1. Zhai S, Tanimura A, Graves SM et al (2018) Striatal synapses, circuits, and Parkinson’s disease. Curr Opin Neurobiol 48:9–16

    Article  CAS  PubMed  Google Scholar 

  2. Albin RL, Young AB, Penney JB (1989) The functional anatomy of basal ganglia disorders. Trends Neurosci 12:366–375

    Article  CAS  PubMed  Google Scholar 

  3. Gittis AH, Kreitzer AC (2012) Striatal microcircuitry and movement disorders. Trends Neurosci 35:557–564

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Gerfen CR, Surmeier DJ (2011) Modulation of striatal projection systems by dopamine. Annu Rev Neurosci 34:441–466

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Gerfen CR, Keefe KA, Gauda EB (1995) D1 and D2 dopamine receptor function in the striatum: coactivation of D1- and D2-dopamine receptors on separate populations of neurons results in potentiated immediate early gene response in D1-containing neurons. J Neurosci 15:8167–8176

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Gerfen CR, Engber TM, Mahan LC et al (1990) D1 and D2 dopamine receptor-regulated gene expression of striatonigral and striatopallidal neurons. Science 250:1429–1432

    Article  CAS  PubMed  Google Scholar 

  7. Kawaguchi Y (1993) Physiological, morphological, and histochemical characterization of three classes of interneurons in rat neostriatum. J Neurosci 13:4908–4923

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Kawaguchi Y, Wilson CJ, Augood SJ et al (1995) Striatal interneurones: chemical, physiological and morphological characterization. Trends Neurosci 18:527–535

    Article  CAS  PubMed  Google Scholar 

  9. Tepper JM, Koos T, Wilson CJ (2004) GABAergic microcircuits in the neostriatum. Trends Neurosci 27:662–669

    Article  CAS  PubMed  Google Scholar 

  10. Straub C, Saulnier JL, Begue A et al (2016) Principles of synaptic organization of GABAergic interneurons in the striatum. Neuron 92:84–92

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Silberberg G, Bolam JP (2015) Local and afferent synaptic pathways in the striatal microcircuitry. Curr Opin Neurobiol 33:182–187

    Article  CAS  PubMed  Google Scholar 

  12. Koos T, Tepper JM (1999) Inhibitory control of neostriatal projection neurons by GABAergic interneurons. Nat Neurosci 2:467–472

    Article  CAS  PubMed  Google Scholar 

  13. Cowan RL, Wilson CJ, Emson PC et al (1990) Parvalbumin-containing GABAergic interneurons in the rat neostriatum. J Comp Neurol 302:197–205

    Article  CAS  PubMed  Google Scholar 

  14. Marin O (2012) Interneuron dysfunction in psychiatric disorders. Nat Rev Neurosci 13:107–120

    Article  CAS  PubMed  Google Scholar 

  15. Mallet N, Ballion B, Le Moine C et al (2006) Cortical inputs and GABA interneurons imbalance projection neurons in the striatum of parkinsonian rats. J Neurosci 26:3875–3884

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Kitai ST, Kocsis JD, Preston RJ et al (1976) Monosynaptic inputs to caudate neurons identified by intracellular injection of horseradish peroxidase. Brain Res 109:601–606

    Article  CAS  PubMed  Google Scholar 

  17. Dube L, Smith AD, Bolam JP (1988) Identification of synaptic terminals of thalamic or cortical origin in contact with distinct medium-size spiny neurons in the rat neostriatum. J Comp Neurol 267:455–471

    Article  CAS  PubMed  Google Scholar 

  18. Deschenes M, Bourassa J, Doan VD et al (1996) A single-cell study of the axonal projections arising from the posterior intralaminar thalamic nuclei in the rat. Eur J Neurosci 8:329–343

    Article  CAS  PubMed  Google Scholar 

  19. Smith AD, Bolam JP (1990) The neural network of the basal ganglia as revealed by the study of synaptic connections of identified neurones. Trends Neurosci 13:259–265

    Article  CAS  PubMed  Google Scholar 

  20. Berendse HW, Groenewegen HJ (1990) Organization of the thalamostriatal projections in the rat, with special emphasis on the ventral striatum. J Comp Neurol 299:187–228

    Article  CAS  PubMed  Google Scholar 

  21. Gerfen CR (1988) Synaptic organization of the striatum. J Electron Microsc Tech 10:265–281

    Article  CAS  PubMed  Google Scholar 

  22. Herkenham M, Pert CB (1981) Mosaic distribution of opiate receptors, parafascicular projections and acetylcholinesterase in rat striatum. Nature 291:415–418

    Article  CAS  PubMed  Google Scholar 

  23. Lacey CJ, Boyes J, Gerlach O et al (2005) GABA(B) receptors at glutamatergic synapses in the rat striatum. Neuroscience 136:1083–1095

    Article  CAS  PubMed  Google Scholar 

  24. Raju DV, Shah DJ, Wright TM et al (2006) Differential synaptology of vGluT2-containing thalamostriatal afferents between the patch and matrix compartments in rats. J Comp Neurol 499:231–243

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Lei W, Jiao Y, Del MN et al (2004) Evidence for differential cortical input to direct pathway versus indirect pathway striatal projection neurons in rats. J neurosci 24:8289–8299

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Dimova R, Vuillet J, Nieoullon A et al (1993) Ultrastructural features of the choline acetyltransferase-containing neurons and relationships with nigral dopaminergic and cortical afferent pathways in the rat striatum. Neuroscience 53:1059–1071

    Article  CAS  PubMed  Google Scholar 

  27. Meredith GE, Chang HT (1994) Synaptic relationships of enkephalinergic and cholinergic neurons in the nucleus accumbens of the rat. Brain Res 667:67–76

    Article  CAS  PubMed  Google Scholar 

  28. Lapper SR, Bolam JP (1992) Input from the frontal cortex and the parafascicular nucleus to cholinergic interneurons in the dorsal striatum of the rat. Neuroscience 51:533–545

    Article  CAS  PubMed  Google Scholar 

  29. Meredith GE, Wouterlood FG (1990) Hippocampal and midline thalamic fibers and terminals in relation to the choline acetyltransferase-immunoreactive neurons in nucleus accumbens of the rat: a light and electron microscopic study. J Comp Neurol 296:204–221

    Article  CAS  PubMed  Google Scholar 

  30. Kachidian P, Vuillet J, Nieoullon A et al (1996) Striatal neuropeptide Y neurones are not a target for thalamic afferent fibres. Neuroreport 7:1665–1669

    Article  CAS  PubMed  Google Scholar 

  31. Vuillet J, Kerkerian L, Kachidian P et al (1989) Ultrastructural correlates of functional relationships between nigral dopaminergic or cortical afferent fibers and neuropeptide Y-containing neurons in the rat striatum. Neurosci Lett 100:99–104

    Article  CAS  PubMed  Google Scholar 

  32. Clarke DJ, Dunnett SB (1993) Synaptic relationships between cortical and dopaminergic inputs and intrinsic GABAergic systems within intrastriatal striatal grafts. J Chem Neuroanat 6:147–158

    Article  CAS  PubMed  Google Scholar 

  33. Roux L, Buzsaki G (2015) Tasks for inhibitory interneurons in intact brain circuits. Neuropharmacology 88:10–23

    Article  CAS  PubMed  Google Scholar 

  34. Smith Y, Raju D, Nanda B et al (2009) The thalamostriatal systems: anatomical and functional organization in normal and parkinsonian states. Brain Res Bull 78:60–68

    Article  CAS  PubMed  Google Scholar 

  35. Rudkin TM, Sadikot AF (1999) Thalamic input to parvalbumin-immunoreactive GABAergic interneurons: organization in normal striatum and effect of neonatal decortication. Neuroscience 88:1165–1175

    Article  CAS  PubMed  Google Scholar 

  36. Sidibe M, Smith Y (1999) Thalamic inputs to striatal interneurons in monkeys: synaptic organization and co-localization of calcium binding proteins. Neuroscience 89:1189–1208

    Article  CAS  PubMed  Google Scholar 

  37. Lapper SR, Smith Y, Sadikot AF et al (1992) Cortical input to parvalbumin-immunoreactive neurones in the putamen of the squirrel monkey. Brain Res 580:215–224

    Article  CAS  PubMed  Google Scholar 

  38. Sciamanna G, Ponterio G, Mandolesi G et al (2015) Optogenetic stimulation reveals distinct modulatory properties of thalamostriatal vs corticostriatal glutamatergic inputs to fast-spiking interneurons. Sci Rep 5:16742

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Hu H, Gan J, Jonas P (2014) Interneurons. Fast-spiking, parvalbumin(+) GABAergic interneurons: from cellular design to microcircuit function. Science 345:1255263

    Article  PubMed  Google Scholar 

  40. Kita H, Kosaka T, Heizmann CW (1990) Parvalbumin-immunoreactive neurons in the rat neostriatum: a light and electron microscopic study. Brain Res 536:1–15

    Article  CAS  PubMed  Google Scholar 

  41. Bennett BD, Bolam JP (1994) Synaptic input and output of parvalbumin-immunoreactive neurons in the neostriatum of the rat. Neuroscience 62:707–719

    Article  CAS  PubMed  Google Scholar 

  42. Schuermann M, Neuberg M, Hunter JB et al (1989) The leucine repeat motif in Fos protein mediates complex formation with Jun/AP-1 and is required for transformation. Cell 56:507–516

    Article  CAS  PubMed  Google Scholar 

  43. Herschman HR (1989) Extracellular signals, transcriptional responses and cellular specificity. Trends Biochem Sci (Amsterdam) 14:455

    Article  CAS  Google Scholar 

  44. Herdegen T, Leah JD, Manisali A et al (1991) c-JUN-like immunoreactivity in the CNS of the adult rat: basal and transynaptically induced expression of an immediate-early gene. Neuroscience 41:643–654

    Article  CAS  PubMed  Google Scholar 

  45. Herdegen T, Kovary K, Leah J et al (1991) Specific temporal and spatial distribution of JUN, FOS, and KROX-24 proteins in spinal neurons following noxious transsynaptic stimulation. J Comp Neurol 313:178–191

    Article  CAS  PubMed  Google Scholar 

  46. Hunt SP, Pini A, Evan G (1987) Induction of c-fos-like protein in spinal cord neurons following sensory stimulation. Nature 328:632–634

    Article  CAS  PubMed  Google Scholar 

  47. Pearse DD, Bushell G, Leah JD (2001) Jun, Fos and Krox in the thalamus after C-fiber stimulation: coincident-input-dependent expression, expression across somatotopic boundaries, and nucleolar translocation. Neuroscience 107:143–159

    Article  CAS  PubMed  Google Scholar 

  48. Li S, Ye F, Farber JP et al (2019) Dependence of c-fos expression on amplitude of high-frequency spinal cord stimulation in a rodent model. Neuromodulation 22:172–178

    Article  PubMed  Google Scholar 

  49. Hitier M, Sato G, Zhang YF et al (2018) Effects of electrical stimulation of the rat vestibular labyrinth on c-Fos expression in the hippocampus. Neurosci Lett 677:60–64

    Article  CAS  PubMed  Google Scholar 

  50. Stiles L, Reynolds JN, Napper R et al (2018) Single neuron activity and c-Fos expression in the rat striatum following electrical stimulation of the peripheral vestibular system. Physiol Rep 6:e13791

    Article  PubMed  PubMed Central  Google Scholar 

  51. Paxinos GWC (1986) The rat brain in stereotaxic coordinates. Elsevier Academic Press, San Diego

    Google Scholar 

  52. Kreitzer AC (2009) Physiology and pharmacology of striatal neurons. Annu Rev Neurosci 32:127–147

    Article  CAS  PubMed  Google Scholar 

  53. Mu S, OuYang L, Liu B et al (2011) Protective effect of melatonin on 3-NP induced striatal interneuron injury in rats. Neurochem Int 59:224–234

    Article  CAS  PubMed  Google Scholar 

  54. Ma Y, Zhan M, OuYang L et al (2014) The effects of unilateral 6-OHDA lesion in medial forebrain bundle on the motor, cognitive dysfunctions and vulnerability of different striatal interneuron types in rats. Behav Brain Res 266:37–45

    Article  CAS  PubMed  Google Scholar 

  55. Mu S, Lin E, Liu B et al (2014) Melatonin reduces projection neuronal injury induced by 3-nitropropionic acid in the rat striatum. Neurodegener Dis 14:139–150

    Article  CAS  PubMed  Google Scholar 

  56. Nakano Y, Karube F, Hirai Y et al (2018) Parvalbumin-producing striatal interneurons receive excitatory inputs onto proximal dendrites from the motor thalamus in male mice. J Neurosci Res 96:1186–1207

    Article  CAS  PubMed  Google Scholar 

  57. Deng YP, Wong T, Bricker-Anthony C et al (2013) Loss of corticostriatal and thalamostriatal synaptic terminals precedes striatal projection neuron pathology in heterozygous Q140 Huntington’s disease mice. Neurobiol Dis 60:89–107

    Article  CAS  PubMed  Google Scholar 

  58. Lei W, Deng Y, Liu B et al (2013) Confocal laser scanning microscopy and ultrastructural study of VGLUT2 thalamic input to striatal projection neurons in rats. J Comp Neurol 521:1354–1377

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Chen S, Yang G, Zhu Y et al (2016) A comparative study of three interneuron types in the rat spinal cord. PLoS One 11:e162969

    Google Scholar 

  60. Reiner A, Hart NM, Lei W et al (2010) Corticostriatal projection neurons—dichotomous types and dichotomous functions. Front Neuroanat 4:142

    Article  PubMed  PubMed Central  Google Scholar 

  61. Liu B, Ouyang L, Mu S et al (2011) The morphological characteristics of corticostriatal and thalamostriatal neurons and their intrastriatal terminals in rats. Surg Radiol Anat 33:807–817

    Article  PubMed  Google Scholar 

  62. Gittis AH, Nelson AB, Thwin MT et al (2010) Distinct roles of GABAergic interneurons in the regulation of striatal output pathways. J Neurosci 30:2223–2234

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Gustafson N, Gireesh-Dharmaraj E, Czubayko U et al (2006) A comparative voltage and current-clamp analysis of feedback and feedforward synaptic transmission in the striatal microcircuit in vitro. J Neurophysiol 95:737–752

    Article  PubMed  Google Scholar 

  64. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Goldberg JH, Tamas G, Yuste R (2003) Ca2+ imaging of mouse neocortical interneurone dendrites: Ia-type K+ channels control action potential backpropagation. J Physiol 551:49–65

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Eggermann E, Jonas P (2011) How the “slow” Ca(2+) buffer parvalbumin affects transmitter release in nanodomain-coupling regimes. Nat Neurosci 15:20–22

    Article  PubMed  PubMed Central  Google Scholar 

  67. Aponte Y, Bischofberger J, Jonas P (2008) Efficient Ca2+ buffering in fast-spiking basket cells of rat hippocampus. J Physiol 586:2061–2075

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Assous M, Tepper JM (2018) Excitatory extrinsic afferents to striatal interneurons and interactions with striatal microcircuitry. Eur J Neurosci 49(5):593–603

    Article  PubMed  PubMed Central  Google Scholar 

  69. Day M, Wang Z, Ding J et al (2006) Selective elimination of glutamatergic synapses on striatopallidal neurons in Parkinson disease models. Nat Neurosci 9:251–259

    Article  CAS  PubMed  Google Scholar 

  70. Parker PR, Lalive AL, Kreitzer AC (2016) Pathway-specific remodeling of thalamostriatal synapses in parkinsonian mice. Neuron 89:734–740

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Calabresi P, Pisani A, Mercuri NB et al (1996) The corticostriatal projection: from synaptic plasticity to dysfunctions of the basal ganglia. Trends Neurosci 19:19–24

    Article  CAS  PubMed  Google Scholar 

  72. Somogyi P (1977) A specific “axo-axonal” interneuron in the visual cortex of the rat. Brain Res 136:345–350

    Article  CAS  PubMed  Google Scholar 

  73. Woo TU, Whitehead RE, Melchitzky DS et al (1998) A subclass of prefrontal gamma-aminobutyric acid axon terminals are selectively altered in schizophrenia. Proc Natl Acad Sci USA 95:5341–5346

    Article  CAS  PubMed  Google Scholar 

  74. Liu B (2011) Morphological characteristics of the striatal neural pathway by biotinylated dextran amine tracing in. Neural Regen Res 6:1931–1936

    CAS  Google Scholar 

  75. Fujiyama F, Unzai T, Nakamura K et al (2006) Difference in organization of corticostriatal and thalamostriatal synapses between patch and matrix compartments of rat neostriatum. Eur J Neurosci 24:2813–2824

    Article  PubMed  Google Scholar 

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (81471288), and by the National Key R&D Program of China (2017YFA0104704).

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  1. Xuefeng Zheng, Liping Sun and Bingbing Liu have contributed equally to this article.

Authors and Affiliations

  1. Department of Anatomy, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China

    Xuefeng Zheng, Ziyun Huang, Yaofeng Zhu, Tao Chen, Linju Jia, Yanmei Li & Wanlong Lei

  2. Department of Anatomy, Neuroscience Laboratory for Cognitive and Developmental Disorders, Medical College of Jinan University, Guangzhou, China

    Xuefeng Zheng

  3. Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China

    Liping Sun

  4. Department of Anesthesiology, Guangdong Second Provincial General Hospital, Guangzhou, China

    Bingbing Liu

  5. Institute of Medicine, College of Medicine, Jishou University, Jishou, China

    Yaofeng Zhu

  6. The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China

    Bingbing Liu

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  1. Xuefeng Zheng
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All animal experiments were performed according to the National Institutes of Health Guide for the Care and Use of Laboratory Animals conducted and approved by the Animal Care and Use Committee of Sun Yat-sen University (ethical permission No.: Zhongshan Medical Ethics 2014-23).

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Zheng, X., Sun, L., Liu, B. et al. Morphological Study of the Cortical and Thalamic Glutamatergic Synaptic Inputs of Striatal Parvalbumin Interneurons in Rats. Neurochem Res 46, 1659–1673 (2021). https://doi.org/10.1007/s11064-021-03302-4

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