Age-Dependent Changes in Dopaminergic Neuron Firing Patterns in Substantia Nigra Pars Compacta

  • Yoshiyuki IshidaEmail author
  • Tatsuya Kozaki
  • Yoshikazu Isomura
  • Sachiko Ito
  • Ken-ichi Isobe
Part of the Journal of Neural Transmission. Supplementa book series (NEURALTRANS, volume 73)


Dopaminergic neurons in the substantia nigra pars compacta modulate complex motor control. Nigral dopaminergic neurons exhibit three different firing patterns in vivo: a pacemaker mode, a random mode, and a burst mode. These firing patterns are closely related to motor control. However, the changes in the proportion of the firing patterns with respect to age have not been fully established. To clarify the age-dependent changes in the proportion of dopaminergic firing patterns, we used single unit extracellular recordings in male F344/N rats. We observed that, with age, the distribution of the spikes fired by dopaminergic neurons shifts from pacemaker to random mode, and then from random to burst mode. These results suggest that the age-dependent changes in the proportion of nigral dopaminergic firing patterns may have an effect on motor function.


Aging Electrophysiology F344 rat Firing pattern Substantia nigra pars compacta 



Coefficient of variation








Substantia nigra pars compacta





The authors thank Ms. Fulva Shah and Dr. James Tepper for technical advice and Dr. Christian Lee for comments on the manuscript. This work was supported by Research Grants for Longevity Sciences (10C-03) from the Ministry of Health, Labour and Welfare of Japan.


  1. Bilbao G, Ruiz-Ortega JA, Miguens N, Ulibarri I, Linazasoro G, Gómez-Urquijo S, Garibi J, Ugedo L (2006) Electrophysiological characterizaion of substantia nigra dopaminergic neurons in partially lesioned rats: Effect of subthalamotomy and levodopa treatment. Brain Res 1084(1):175–184CrossRefPubMedGoogle Scholar
  2. Campbell A, Baldessarini RJ, Stoll A, Teicher MH, Maynard P (1984) Effect of age on behavioral responses and tissue levels of apomorphine in the rat. Neuropharmacology 23(7A):725–730CrossRefPubMedGoogle Scholar
  3. Chergui K, Suaud-Chagny MF, Gonon F (1994) Nonlinear relationship between impulse flow, dopamine release and dopamine elimination in the rat brain in vivo. Neuroscience 62(3):641–645CrossRefPubMedGoogle Scholar
  4. Deniau JM, Hammond C, Riszk A, Feger J (1978) Electrophysiological properties of identified output neurons of the rat substantia nigra (pars compacta and pars reticulata): evidences for the existence of branched neurons. Exp Brain Res 32:409–422CrossRefPubMedGoogle Scholar
  5. Freeman AS, Kelland MD, Rouillard C, Chiodo LA (1989) Electrophysiological characteristics and pharmacological responsiveness of midbrain dopaminergic neurons of the aged rat. J Pharmacol Exp Ther 249(3):790–797PubMedGoogle Scholar
  6. Freeman AS, Meltzer LT, Bunny BS (1985) Firing properties of substantia nigra dopaminergic neurons in freely moving rats. Life Sci. 36(20):1983–1994Google Scholar
  7. Gonon FG (1988) Nonlinear relationship between impulse flow and dopamine released by rat midbrain dopaminergic neurons as studied by in vivo electrochemistry. Neuroscience 24(1):19–28CrossRefPubMedGoogle Scholar
  8. Grace AA, Bunney BS (1984) The control of firing pattern in nigral dopamine neurons: burst firing. J Neurosci 4(11):2877–2890PubMedGoogle Scholar
  9. Guyenet PG, Aghajanian GK (1978) Antidromic identification of dopaminergic and other output neurons of the rat substantia nigra. Brain Res 150:69–84CrossRefPubMedGoogle Scholar
  10. Hebert MA, Gerhardt GA (1998) Normal and drug-induced locomotor behavior in aging: comparison to evoked DA release and tissue content in fischer 344 rats. Brain Res 797(1):42–54CrossRefPubMedGoogle Scholar
  11. Hyland BI, Reynolds JN, Hay J, Perk CG, Miller R (2002) Firing modes of midbrain dopamine cells in the freely moving rat. Neuroscience 114:475–492CrossRefGoogle Scholar
  12. Ishida Y, Okawa Y, Ito S, Shirokawa T, Isobe K (2007) Age-dependent changes in dopaminergic projections from the substantia nigra pars compacta to the neostriatum. Neurosci Lett 418(3):257–261CrossRefPubMedGoogle Scholar
  13. Payne AP, Campbell JM, Russell D, Favor G, Sutcliffe RG, Bennett NK, Davies RW, Stone TW (2000) The AS/AGU rat: a spontaneous model of disruption and degeneration in the nigrostriatal dopaminergic system. J Anat 196:629–633CrossRefPubMedGoogle Scholar
  14. Sakata M, Farooqui SM, Prasad C (1992) Post-transcriptional regulation of loss of rat striatal D2 dopamine receptor during aging. Brain Res 575(2):309–314CrossRefPubMedGoogle Scholar
  15. Schultz W, Dayan P, Montague PR (1997) A neural substrate of prediction and reward. Science 275(5306):1593–1599CrossRefPubMedGoogle Scholar
  16. Suzuki M, Hatano K, Sakiyama Y, Kawasumi Y, Kato T, Ito K (2001) Age-related changes of dopamine D1-like and D2-like receptor binding in the F344/N rat striatum revealed by positron emission tomography and in vitro receptor autoradiography. Synapse 41(4):285–293CrossRefPubMedGoogle Scholar
  17. Tepper JM, Martin LP, Anderson DR (1995) GABAA receptor-mediated inhibition of rat substantia nigra dopaminergic neurons by pars reticulata projection neurons. J Neurosci 15(4):3092–3103PubMedGoogle Scholar
  18. Wilson CJ, Young SJ, Groves PM (1977) Statistical properties of neuronal spike trains in the substantia nigra: cell types and their interactions. Brain Res 136(2):243–260CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag/Wien Printed in Germany 2009

Authors and Affiliations

  • Yoshiyuki Ishida
    • 1
    • 2
    Email author
  • Tatsuya Kozaki
    • 3
  • Yoshikazu Isomura
    • 4
  • Sachiko Ito
    • 3
  • Ken-ichi Isobe
    • 2
    • 3
  1. 1.Radioisotope Research CenterNagoya University Graduate School of MedicineAichiJapan
  2. 2.Department of Mechanism of AgingNational Institute for Longevity SciencesAichiJapan
  3. 3.Department of ImmunologyNagoya University Graduate School of MedicineNagoyaJAPAN
  4. 4.Neural Circuit TheoryRIKEN Brain Science InstituteWako CityJAPAN

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