Neurochemical and Structural Organization of the Principal Nucleus of the Inferior Olive in the Human

Abstract

The inferior olive (IO) is the sole source of the climbing fibers that innervate the Purkinje cells of the cerebellar cortex. The IO comprises several subdivisions, the dorsal accessory olive (DAO), medial accessory olive (MAO), and principal nuclei of the IO (IOpr); the relative sizes of these subnuclei vary among species. In human, there is an expansion of the cerebellar hemispheres and a corresponding expansion of the IOpr. We have examined the structural and neurochemical organization of the human IOpr, using sections stained with cresyl violet (CV) or immunostained for the calcium-binding proteins calbindin (CB), calretinin (CR), and parvalbumin (PV), the synthetic enzyme for nitric oxide (nNOS), and nonphosphorylated neurofilament protein (NPNFP). We found qualitative differences in the folding patterns of the IOpr among individuals and between the two sides of the brainstem. Quantification of IOpr volumes and indices of folding complexity, however, did not reveal consistent left-right differences in either parameter. Single-label immunohistochemistry showed that populations of neurons in the IOpr express CB, CR, NPNFP, and nNOS. Individual fibers labeled for PV, CB, CR, NPNFP, and nNOS were also found. There was individual variability in the numbers and density of stained neurons in the human IOpr; such variability was not seen in other brainstem nuclei. These data are consistent with, and complement, earlier studies showing a dramatic age-related increase in lipofuscin and decrease in RNA in the human IOpr. The impact of these changes in the IOpr on cerebellar function is, however, not known. Anat Rec, 294:1198Rec, 294: -1216Rec, 294: , 2011. V V C 2011 Wiley-Liss, Inc.

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“…To test this idea, we compared two measurements for the left and right, volume and an index of folding complexity. We did not find that the IOpr was larger or had a more complex folding pattern in the side contralateral to the preferred hand (Baizer et al, 2011b). There may be more subtle measurements like cell packing density, sizes of cells, thickness of the IOpr ribbon, or total number of cells that would show differences correlated with handedness.…”

“…We asked if these left–right differences in the IOpr might be related to handedness. We compared the volume and a measure of folding complexity of the IOpr for the left and right sides but did not find a significant difference (Baizer et al, 2011b). Left–right differences in folding pattern can also be observed in the IOpr of the chimpanzee (Figure 6).…”

“…We also photographed sections from the cat, macaque, squirrel monkey, and rat that had been prepared in this laboratory in the context of several different projects (Baizer and Baker, 2005, 2006b; Baizer et al, 2007, 2011a,b, 2013b,c; Baizer, 2008, 2009; Baizer and Broussard, 2010; Sultan et al, 2010). The methods and results for each project were described in detail in the individual publications.…”

“…Use of this tissue was approved by the IRB at the University at Buffalo. For one project, the study of the inferior olive (IO), we also used samples from the Mount Sinai School of Medicine (MSSM) Brain Bank; sections from a case at the Barrow Neurological Institute were used to develop a 3D model of the principal nucleus of the inferior olive (IOpr; Baizer et al, 2011b). Table 1 shows critical parameters for the cases.…”

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“…These results show a laminar organization that is similar to that of other species. We have also begun studying the neurochemical organization of the human DCN using immunoreactivity to different markers that have been useful in understanding the organization of other brainstem structures (Baizer et al, 2007; Baizer and Broussard, 2010; Baizer et al, 2011). Figure 7C shows expression of nonphosphorylated neurofilament protein (NPNFP, “SMI32” antibody) in the DCN.…”