Computer-assisted 3D reconstruction of the human basal forebrain complex

Grinberg, Lea Tenenholz; Heinsen, Helmut

doi:10.1590/S1980-57642008DN10200005

Abstract

The basal forebrain complex (BFC) is a small but intricate structure. Its organization and function is hard to investigate using conventional methods, especially in humans. By combining new methods of research we present a comprehensive overview of this complex, in order to better understand its function in normal and diseased brains.

Methods:

The right and left BFC of a 29-year-old male were reconstructed from gallcocyanin (Nissl) stained 440 mm-thick serial horizontal sections by using advanced computer-assisted 3D reconstruction software.

Results:

The reconstructed components in the present case include Ch2, Ch3, Ch4am-al, Ch4i, Ch4p, juxtacommissural, Ayala's medial (subpallidal) and lateral (periputaminal) subnuclei. These components are arranged in an arch-like course mainly beneath the anterior commissure. The bilateral volume of all subnuclei was 99.06 mm³, the left side accounting for 48.05 mm³. Some of the subnuclei exhibited volume asymmetry indices varying from 28.3 to 12.9%.The volume of Ayalas' lateral or periputaminal nucleus was 9.7% higher on the right, than on the left side.

Conclusions:

Our methodological approach promises to be highly efficient and reproducible in studying morphofunctional correlations in complex cognitive features

Key words:
human; adults; models/ structural; substantia innominata; nucleus basalis of Meynert; quantitative analysis; neurons/cytology.

Resumo

O complexo prosencefálico basal (CPB) é uma estrutura complicada, apesar de pequena. É difícil estudar sua organização e função por métodos convencionais, especialmente em humanos. Ao combinar novos métodos de investigação, apresentamos uma abordagem completa deste complexo, com objetivo de auxiliar a compreensão de sua função em cérebros controles e acometidos por doenças.

Métodos:

Os CPBs direito e esquerdo de um homem de 29 anos de idade foram reconstruídos tridimensionalmente com uso de um software potente, à partir de secções histológicas horizontais de 440 mm de espessura.

Resultados:

Os núcleos reconstruídos no presente caso são: Ch2, Ch3, Ch4am-al, Ch4i, Ch4p, e os subnúcleos juxtacommissural, Ayala medial (ou subpalidal) e lateral (periputaminal). Essas estruturas se arranjam em forma de arco, praticamente acompanhando a comissura anterior. O volume bilateral de todas as estruturas é de 99.06 mm³, sendo que o lado esquerdo responde por 48.05 mm³. Alguns dos subnúcleos exibem índices de assimetria variando de 28.3 a 12.9%. O volume do subnúcleo de Ayala lateral ou periputaminal é 9.7% maior à direita.

Conclusão:

O método apresentado tem grande potencial de ser bastante eficiente e reprodutível para estudos de correlação morfofuncional relacionadas a características cognitivas complexas.

Palavras-chave:
humano; adulto; modelos/estruturas; substância innominata; núcleo basal de Meynert; análise quantitativa; neurônios; citologia.

Texto completo disponível apenas em PDF.

Full text available only in PDF format.

References

¹
Mesulam MM. The cholinergic contribution to neuromodulation in the cerebral cortex. Semin Neurosci 1995;7:297-307.
²
Heimer L, van Hoesen GW. The limbic lobe and its output channels: implications for emotional functions and adaptive behavior. Neurosci Biobehav Rev 2006;30:126-147.
³
Mesulam MM, Mufson EJ, Wainer BH, Levey AI. Central cholinergic pathways in the rat: an overview based on an alternative nomenclature (Ch1-Ch6). Neuroscience 1983;10:1185-1201.
⁴
Selden NR, Gitelman DR, Salamon-Murayama N, Parrish TB, Mesulam MM. Trajectories of cholinergic pathways within the cerebral hemispheres of the human brain. Brain 1998;121:2249-2257.
⁵
Alonso JR, U HS, Amaral DG. Cholinergic innervation of the primate hippocampal formation: II. Effects of fimbria/fornix transection. J Comp Neurol 1996;375:527-551.
⁶
Simic G, Mrzljak L, Fucic A, Winblad B, Lovric H, Kostovic I. Nucleus subputaminalis (Ayala): the still disregarded magnocellular component of the basal forebrain may be human specific and connected with the cortical speech area. Neuroscience 1999;89:73-89.
⁷
Heinsen H, Hampel H, Teipel SJ. Nucleus subputaminalis: neglected part of the basal nucleus of Meynert - Response to Boban et al: computer-assisted 3D reconstruction of the nucleus basalis complex, including the nucleus subputaminalis (Ayala's nucleus). Brain 2006;129:U1-U4.
⁸
Arendt T, Bigl V, Arendt A, Tennstedt A. Loss of neurons in the nucleus basalis of Meynert in Alzheimer's disease, paralysis agitans and Korsakoff's Disease. Acta Neuropathol 1983;61:101-108.
⁹
Sassin I, Schultz C, Thal DR, et al. Evolution of Alzheimer's disease-related cytoskeletal changes in the basal nucleus of Meynert. Acta Neuropathol 2000;100:259-269.
¹⁰
Hauw JJ, Agid Y. Progressive supranuclear palsy (PSP) or Steele-Richardson-Olszewski disease. In: Dickson DW, editor. Neurodegeneration: the molecular pathology of dementia and movement disorders Neurodegeneration: the molecular pathology of dementia and movement disorders. Basel: ISN Neuropath Press; 2003:103-114.
¹¹
Dickson DW, Bergeron C, Chin SS, et al. Office of rare diseases neuropathologic criteria for corticobasal degeneration. J Neuropathol Exp Neurol 2002;61:935-946.
¹²
Mesulam MM, Mufson EJ, Levey AI, Wainer BH. Cholinergic innervation of cortex by the basal forebrain: cytochemistry and cortical connections of the septal area, diagonal band nuclei, nucleus basalis (substantia innominata), and hypothalamus in the rhesus monkey. J Comp Neurol 1983;214:170-197.
¹³
Geula C, Schatz CR, Mesulam MM. Differential localization of NADPH-diaphorase and calbindin- d(28k) within the cholinergic neurons of the basal forebrain, striatum and brainstem in the rat, monkey, baboon and human. Neuroscience 1993;54:461-476.
¹⁴
Mesulam MM, Hersh LB, Mash DC, Geula C. Differential cholinergic innervation within functional subdivisions of the human cerebral cortex: a choline acetyltransferase study. J Comp Neurol 1992;318:316-328.
¹⁵
Heinsen H, Arzberger T, Schmitz C. Celloidin mounting (embedding without infiltration) - a new, simple and reliable method for producing serial sections of high thickness through complete human brains and its application to stereological and immunohistochemical investigations. J Chem Neuroanat 2000;20:49-59.
¹⁶
Mesulam MM. Cholinergic pathways and the ascending reticular activating system of the human brain. Ann N Y Acad Sci 1995;757:169-179.
¹⁷
Boban M, Kostovic I, Simic G. Nucleus subputaminalis: neglected part of the basal nucleus of Meynert. Brain 2006;129:2005-2006.
¹⁸
Eidelberg D, Galaburda AM. Symmetry and asymmetry in the human posterior thalamus. Arch Neurol 1982;39:325-332.
¹⁹
Hedreen JC, Struble RG, Whitehouse PJ, Price DL. Topography of the magnocellular basal forebrain system in human brain. J Neuropathol Exp Neurol 1984;43:1-21.
²⁰
Arendt T, Bigl V, Tennstedt A, Arendt A. Correlation between cortical plaque count and neuronal loss in the nucleus basalis in Alzheimer's disease. Neurosci Lett 1984;48:81-85.
²¹
Arendt T, Bigl V, Tennstedt A, Arendt A. Neuronal loss in different parts of the nucleus basalis is related to neuritic plaque formation in cortical target areas in Alzheimer's disease. Neuroscience 1985;14:1-14.
²²
Cullen KM, Halliday GM, Double KL, Brooks WS, Creasey H, Broe GA. Cell loss in the nucleus basalis is related to regional cortical atrophy in Alzheimer's disease. Neuroscience 1997;78:641-652.
²³
Cullen KM, Halliday GM. Neurofibrillary degeneration and cell loss in the nucleus basalis in comparison to cortical Alzheimer pathology. Neurobiol Aging 1998;19:297-306.
²⁴
Lehericy S, Hirsch EC, Cerverapierot P, et al. Heterogeneity and selectivity of the degeneration of cholinergic neurons in the basal forebrain of patients with Alzheimer's disease. J Comp Neurol 1993;330:15-31.
²⁵
McGeer PL, McGeer EG, Suzuki J, Dolman CE, Nagai T. Aging, Alzheimer's disease, and the cholinergic system of the basal forebrain. Neurology 1984;34:741-745.
²⁶
Whitehouse PJ, Price DL, Clark AW, Coyle JT, DeLong MR. Alzheimer disease: evidence for selective loss of cholinergic neurons in the nucleus basalis. Ann Neurol 1981;10:122-126.
²⁷
Teipel SJ, Flatz WH, Heinsen H, et al. Measurement of basal forebrain atrophy in Alzheimer's disease using MRI. Brain 2005;128:2626-2644.
²⁸
Amunts VV. Structural asymmetry of the basal nucleus of Meynert in men and women. Zh Nevrol Psikhiatr Im S S Korsakova 2006;106:50-54.
²⁹
Doucette R, Ball MJ. Left-right symmetry of neuronal cell counts in the nucleus basalis of Meynert of control and of Alzheimer-diseased brains. Brain Res 1987;422:357-360.
³⁰
Lowes-Hummel P, Gertz HJ, Ferszt R, Cervos-Navarro J. The basal nucleus of Meynert revised: the nerve cell number decreases with age. Arch Gerontol Geriatr 1989;8:21-27.
³¹
Vogels OJ, Broere CA, Ter Laak HJ, Ten Donkelaar HJ, Nieuwenhuys R, Schulte BP. Cell loss and shrinkage in the nucleus basalis Meynert complex in Alzheimer's disease. Neurobiol Aging 1990;11:3-13.
³²
Zubenko GS, Moossy J, Hanin I, Martinez AJ, Rao GR, Kopp U. Bilateral symmetry of cholinergic deficits in Alzheimer's disease. Arch Neurol 1988;45:255-259.
³³
Halliday GM, Cullen K, Cairns MJ. Quantitation and three-dimensional reconstruction of Ch4 nucleus in the human basal forebrain. Synapse 1993;15:1-16.
³⁴
Lewis PR, Shute CC. The cholinergic limbic system: projections to hippocampal formation, medial cortex, nuclei of the ascending cholinergic reticular system, and the subfornical organ and supra-optic crest. Brain 1967;90:521-540.
³⁵
Kievit J, Kuypers HG. Subcortical afferents to the frontal lobe in the rhesus monkey studied by means of retrograde horseradish peroxidase transport. Brain Res 1975;85:261-266.
³⁶
Mesulam MM, Mufson EJ. Neural inputs into the nucleus basalis of the substantia innominata (Ch4) in the rhesus monkey. Brain 1984;107:253-274.
³⁷
Rye DB, Wainer BH, Mesulam MM, Mufson EJ, Saper CB. Cortical projections arising from the basal forebrain: a study of cholinergic and noncholinergic components employing combined retrograde tracing and immunohistochemical localization of choline acetyltransferase. Neuroscience 1984;13:627-643.
³⁸
Jones BE, Cuello AC. Afferents to the basal forebrain cholinergic cell area from pontomesencephalic - catecholamine, serotonin, and acetylcholine - neurons. Neuroscience 1989;31:37-61.
³⁹
Russchen FT, Amaral DG, Price JL. The afferent connections of the substantia innominata in the monkey, Macaca fascicularis. J Comp Neurol 1985;242:1-27.
⁴⁰
Mesulam MM. The systems-level organization of cholinergic innervation in the human cerebral cortex and its alterations in Alzheimer's disease. Prog Brain Res 1996;109:285-297.
⁴¹
Gaykema RP, Zaborszky L. Direct catecholaminergic-cholinergic interactions in the basal forebrain. II. Substantia nigra-ventral tegmental area projections to cholinergic neurons. J Comp Neurol 1996;374:555-577.

Publication Dates

Publication in this collection
Apr-Jun 2007

This is an open-access article distributed under the terms of the Creative Commons Attribution License

[1] ¹
Mesulam MM. The cholinergic contribution to neuromodulation in the cerebral cortex. Semin Neurosci 1995;7:297-307.

[2] ²
Heimer L, van Hoesen GW. The limbic lobe and its output channels: implications for emotional functions and adaptive behavior. Neurosci Biobehav Rev 2006;30:126-147.

[3] ³
Mesulam MM, Mufson EJ, Wainer BH, Levey AI. Central cholinergic pathways in the rat: an overview based on an alternative nomenclature (Ch1-Ch6). Neuroscience 1983;10:1185-1201.

[4] ⁴
Selden NR, Gitelman DR, Salamon-Murayama N, Parrish TB, Mesulam MM. Trajectories of cholinergic pathways within the cerebral hemispheres of the human brain. Brain 1998;121:2249-2257.

[5] ⁵
Alonso JR, U HS, Amaral DG. Cholinergic innervation of the primate hippocampal formation: II. Effects of fimbria/fornix transection. J Comp Neurol 1996;375:527-551.

[6] ⁶
Simic G, Mrzljak L, Fucic A, Winblad B, Lovric H, Kostovic I. Nucleus subputaminalis (Ayala): the still disregarded magnocellular component of the basal forebrain may be human specific and connected with the cortical speech area. Neuroscience 1999;89:73-89.

[7] ⁷
Heinsen H, Hampel H, Teipel SJ. Nucleus subputaminalis: neglected part of the basal nucleus of Meynert - Response to Boban et al: computer-assisted 3D reconstruction of the nucleus basalis complex, including the nucleus subputaminalis (Ayala's nucleus). Brain 2006;129:U1-U4.

[8] ⁸
Arendt T, Bigl V, Arendt A, Tennstedt A. Loss of neurons in the nucleus basalis of Meynert in Alzheimer's disease, paralysis agitans and Korsakoff's Disease. Acta Neuropathol 1983;61:101-108.

[9] ⁹
Sassin I, Schultz C, Thal DR, et al. Evolution of Alzheimer's disease-related cytoskeletal changes in the basal nucleus of Meynert. Acta Neuropathol 2000;100:259-269.

[10] ¹⁰
Hauw JJ, Agid Y. Progressive supranuclear palsy (PSP) or Steele-Richardson-Olszewski disease. In: Dickson DW, editor. Neurodegeneration: the molecular pathology of dementia and movement disorders Neurodegeneration: the molecular pathology of dementia and movement disorders. Basel: ISN Neuropath Press; 2003:103-114.

[11] ¹¹
Dickson DW, Bergeron C, Chin SS, et al. Office of rare diseases neuropathologic criteria for corticobasal degeneration. J Neuropathol Exp Neurol 2002;61:935-946.

[12] ¹²
Mesulam MM, Mufson EJ, Levey AI, Wainer BH. Cholinergic innervation of cortex by the basal forebrain: cytochemistry and cortical connections of the septal area, diagonal band nuclei, nucleus basalis (substantia innominata), and hypothalamus in the rhesus monkey. J Comp Neurol 1983;214:170-197.

[13] ¹³
Geula C, Schatz CR, Mesulam MM. Differential localization of NADPH-diaphorase and calbindin- d(28k) within the cholinergic neurons of the basal forebrain, striatum and brainstem in the rat, monkey, baboon and human. Neuroscience 1993;54:461-476.

[14] ¹⁴
Mesulam MM, Hersh LB, Mash DC, Geula C. Differential cholinergic innervation within functional subdivisions of the human cerebral cortex: a choline acetyltransferase study. J Comp Neurol 1992;318:316-328.

[15] ¹⁵
Heinsen H, Arzberger T, Schmitz C. Celloidin mounting (embedding without infiltration) - a new, simple and reliable method for producing serial sections of high thickness through complete human brains and its application to stereological and immunohistochemical investigations. J Chem Neuroanat 2000;20:49-59.

[16] ¹⁶
Mesulam MM. Cholinergic pathways and the ascending reticular activating system of the human brain. Ann N Y Acad Sci 1995;757:169-179.

[17] ¹⁷
Boban M, Kostovic I, Simic G. Nucleus subputaminalis: neglected part of the basal nucleus of Meynert. Brain 2006;129:2005-2006.

[18] ¹⁸
Eidelberg D, Galaburda AM. Symmetry and asymmetry in the human posterior thalamus. Arch Neurol 1982;39:325-332.

[19] ¹⁹
Hedreen JC, Struble RG, Whitehouse PJ, Price DL. Topography of the magnocellular basal forebrain system in human brain. J Neuropathol Exp Neurol 1984;43:1-21.

[20] ²⁰
Arendt T, Bigl V, Tennstedt A, Arendt A. Correlation between cortical plaque count and neuronal loss in the nucleus basalis in Alzheimer's disease. Neurosci Lett 1984;48:81-85.

[21] ²¹
Arendt T, Bigl V, Tennstedt A, Arendt A. Neuronal loss in different parts of the nucleus basalis is related to neuritic plaque formation in cortical target areas in Alzheimer's disease. Neuroscience 1985;14:1-14.

[22] ²²
Cullen KM, Halliday GM, Double KL, Brooks WS, Creasey H, Broe GA. Cell loss in the nucleus basalis is related to regional cortical atrophy in Alzheimer's disease. Neuroscience 1997;78:641-652.

[23] ²³
Cullen KM, Halliday GM. Neurofibrillary degeneration and cell loss in the nucleus basalis in comparison to cortical Alzheimer pathology. Neurobiol Aging 1998;19:297-306.

[24] ²⁴
Lehericy S, Hirsch EC, Cerverapierot P, et al. Heterogeneity and selectivity of the degeneration of cholinergic neurons in the basal forebrain of patients with Alzheimer's disease. J Comp Neurol 1993;330:15-31.

[25] ²⁵
McGeer PL, McGeer EG, Suzuki J, Dolman CE, Nagai T. Aging, Alzheimer's disease, and the cholinergic system of the basal forebrain. Neurology 1984;34:741-745.

[26] ²⁶
Whitehouse PJ, Price DL, Clark AW, Coyle JT, DeLong MR. Alzheimer disease: evidence for selective loss of cholinergic neurons in the nucleus basalis. Ann Neurol 1981;10:122-126.

[27] ²⁷
Teipel SJ, Flatz WH, Heinsen H, et al. Measurement of basal forebrain atrophy in Alzheimer's disease using MRI. Brain 2005;128:2626-2644.

[28] ²⁸
Amunts VV. Structural asymmetry of the basal nucleus of Meynert in men and women. Zh Nevrol Psikhiatr Im S S Korsakova 2006;106:50-54.

[29] ²⁹
Doucette R, Ball MJ. Left-right symmetry of neuronal cell counts in the nucleus basalis of Meynert of control and of Alzheimer-diseased brains. Brain Res 1987;422:357-360.

[30] ³⁰
Lowes-Hummel P, Gertz HJ, Ferszt R, Cervos-Navarro J. The basal nucleus of Meynert revised: the nerve cell number decreases with age. Arch Gerontol Geriatr 1989;8:21-27.

[31] ³¹
Vogels OJ, Broere CA, Ter Laak HJ, Ten Donkelaar HJ, Nieuwenhuys R, Schulte BP. Cell loss and shrinkage in the nucleus basalis Meynert complex in Alzheimer's disease. Neurobiol Aging 1990;11:3-13.

[32] ³²
Zubenko GS, Moossy J, Hanin I, Martinez AJ, Rao GR, Kopp U. Bilateral symmetry of cholinergic deficits in Alzheimer's disease. Arch Neurol 1988;45:255-259.

[33] ³³
Halliday GM, Cullen K, Cairns MJ. Quantitation and three-dimensional reconstruction of Ch4 nucleus in the human basal forebrain. Synapse 1993;15:1-16.

[34] ³⁴
Lewis PR, Shute CC. The cholinergic limbic system: projections to hippocampal formation, medial cortex, nuclei of the ascending cholinergic reticular system, and the subfornical organ and supra-optic crest. Brain 1967;90:521-540.

[35] ³⁵
Kievit J, Kuypers HG. Subcortical afferents to the frontal lobe in the rhesus monkey studied by means of retrograde horseradish peroxidase transport. Brain Res 1975;85:261-266.

[36] ³⁶
Mesulam MM, Mufson EJ. Neural inputs into the nucleus basalis of the substantia innominata (Ch4) in the rhesus monkey. Brain 1984;107:253-274.

[37] ³⁷
Rye DB, Wainer BH, Mesulam MM, Mufson EJ, Saper CB. Cortical projections arising from the basal forebrain: a study of cholinergic and noncholinergic components employing combined retrograde tracing and immunohistochemical localization of choline acetyltransferase. Neuroscience 1984;13:627-643.

[38] ³⁸
Jones BE, Cuello AC. Afferents to the basal forebrain cholinergic cell area from pontomesencephalic - catecholamine, serotonin, and acetylcholine - neurons. Neuroscience 1989;31:37-61.

[39] ³⁹
Russchen FT, Amaral DG, Price JL. The afferent connections of the substantia innominata in the monkey, Macaca fascicularis. J Comp Neurol 1985;242:1-27.

[40] ⁴⁰
Mesulam MM. The systems-level organization of cholinergic innervation in the human cerebral cortex and its alterations in Alzheimer's disease. Prog Brain Res 1996;109:285-297.

[41] ⁴¹
Gaykema RP, Zaborszky L. Direct catecholaminergic-cholinergic interactions in the basal forebrain. II. Substantia nigra-ventral tegmental area projections to cholinergic neurons. J Comp Neurol 1996;374:555-577.

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