Brain Structure and Function

, Volume 223, Issue 4, pp 1667–1681 | Cite as

Individual variability in the structural properties of neurons in the human inferior olive

  • Joan S. Baizer
  • Keit Men Wong
  • Chet C. Sherwood
  • Patrick R. Hof
  • Sandra F. Witelson
Original Article


The inferior olive (IO) is the sole source of the climbing fibers innervating the cerebellar cortex. We have previously shown both individual differences in the size and folding pattern of the principal nucleus (IOpr) in humans as well as in the expression of different proteins in IOpr neurons. This high degree of variability was not present in chimpanzee samples. The neurochemical differences might reflect static differences among individuals, but might also reflect age-related processes resulting in alterations of protein synthesis. Several observations support the latter idea. First, accumulation of lipofuscin, the “age pigment” is well documented in IOpr neurons. Second, there are silver- and abnormal tau-immunostained intraneuronal granules in IOpr neurons (Ikeda et al. Neurosci Lett 258:113–116, 1998). Finally, Olszewski and Baxter (Cytoarchitecture of the human brain stem, Second edn. Karger, Basel, 1954) observed an apparent loss of IOpr neurons in older individuals. We have further investigated the possibility of age-related changes in IOpr neurons using silver- and immunostained sections. We found silver-labeled intraneuronal granules in neurons of the IOpr in all human cases studied (n = 17, ages 25–71). We did not, however, confirm immunostaining with antibodies to abnormal tau. There was individual variability in the density of neurons as well as in the expression of the calcium-binding protein calretinin. In the chimpanzee, there were neither silver-stained intraneuronal granules nor irregularities in immunostaining. Overall, the data support the hypothesis that in some, but not all, humans there are functional changes in IOpr neurons and ultimately cell death. Neurochemical changes of IOpr neurons may contribute to age-related changes in motor and cognitive skills mediated by the cerebellum.


Cerebellar cortex Purkinje cells Aging Climbing fibers Lysosomes Lipofuscin Hyperphosphorylated tau protein Tauopathies 



We are grateful to Matthew Stone, Yaechan Choi and Jessica Kichigin for help with immunohistochemistry and the plotting of IOpr sections. Supported in part by the Department of Physiology and Biophysics, University at Buffalo. We thank the National Chimpanzee Brain Resource, NS092988, for the chimpanzee brainstems.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  • Joan S. Baizer
    • 1
  • Keit Men Wong
    • 1
  • Chet C. Sherwood
    • 2
  • Patrick R. Hof
    • 3
  • Sandra F. Witelson
    • 4
  1. 1.Department of Physiology and Biophysics, School of Medicine and Biomedical SciencesUniversity at BuffaloBuffaloUSA
  2. 2.Department of Anthropology and Center for the Advanced Study of Human PaleobiologyThe George Washington UniversityWashingtonUSA
  3. 3.Fishberg Department of Neuroscience and Friedman Brain InstituteIcahn School of Medicine at Mount SinaiNew YorkUSA
  4. 4.Department of Psychiatry and Behavioural Neurosciences, Michael G. DeGroote School of MedicineMcMaster UniversityHamiltonCanada

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