Electron Microscopy

Overview

The lab opened in 1966 when Dr. Alan Peters assumed the position of Waterhouse Professor and Chairman of the Department of Anatomy, as it was known then. The focus of the lab was electron microscopy, the goal, to characterize the fine structure of synapses and cell types, neurons and neuroglia, in the cerebral cortex.

Over the past several years we have examined the organization of neurons in cerebral cortex, with emphasis on the pyramidal cell modules. But more recently our focus has been on the effects of aging on primary cerebral cortex and white matter.

electron

The pyramidal cell module By combining the results of careful cell counts, with antibody studies we have defined the pyramidal cell module, which we propose to be the smallest functional unit of cortex.(Figure A)

The cells in figure B and C are stained with an antibody to Calbindin. Photographed with Nomarsky optics, (figure B) bundles of axons are clearly visible as they cascade below the cell bodies. When visualized with a fluorescent marker and viewed in cross section on the confocal microscope (figure C) each bundle of axons appear as a brightly staining cluster.

With the addition of immunocytochemistry and confocal microscopy we have been able to modify the original diagram to include some of the inhibitory neurons in the modules (figure D).

We are now focusing on the effects of normal aging on the cerebral cortex and white matter. To carry out these studies we use electron microscopy, confocal microscopy, antibodies, and stereology, to try to determine which of the morphological changes that occur with age are responsible for the cognitive decline exhibited by aging primates.

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This pair of electron micrographs illustrates some of the changes that occur in visual cortex with age. On the far left is an example of young, normal, myelinated axons. In an aging cortex, the myelin sheaths exhibit changes such as splits, ballooning, and dark cytoplasmic inclusions.

Publications

The most recent publications from our laboratory have been concerned with the effects of normal aging on cerebral cortex and white matter tracts of the monkey brain. Some of these publications are listed below. For a complete list of publications please see the individual pages for the members of our laboratory.

Peters, A. and Sethares, C. 1997 The organization of double bouquet cells in monkey striate cortex. J. Neurocytol. 26: 779- 797.

Peters, A. and Sethares, C. 2002 The effects of age on the cells in layer 1 of primate cerebral cortex. Cerebr. Cortex. 12: 27 Ð 36

Peters A. and Sethares C. 2003 Is there remyelination during aging of the primate central nervous system? J. Comp. Neurol. 460: 238 Ð 254.

Peters A. and Rosene D.L. 2003. In aging, is it gray or white? J. Comp. Neurol. 462 : 139 Ð 143.

Sandell J.H. and Peters A. 2003 Disrupted myelin and axon loss in the anterior commissure of the aged rhesus monkey. J. Comp. Neurol. 466: 14 Ð 30.

Peters, A., S.L. Palay and H. deF. Webster (eds.) 1991 The Fine Structure of the Nervous System. Neurons and their Supporting Cells. Third Edition, Oxford University Press, N.Y

Bertram R. Payne and Alan Peters (eds) 2002 The Cat Primary Visual Cortex. Academic Press. San Diego.

Methodology

Since the focus of the laboratory is electron microscopy, most techniques used in the lab, or developed here are designed specifically for the electron microscope. For example, the Golgi-electron microscope technique 1, allows stained neurons to be first studied by light microscopy, and then their axons and dendrites examined by electron microscopy to ascertain their synaptic relationships.

We also developed a Myelin staining technique 2 , useful both in the light microscopic analysis and electron microscopic analysis of myelin sheaths in cortex. As antibodies became available they have allowed us to study specific types of local circuit neurons in cortex. Immunocytochemical staining has been useful to ascertain how the pyramidal cells are organized into modules at both the light and electron microscopic levels. However, employing fluorescent markers allows us to further investigate the relationship between pyramidal cells and interneurons using the Confocal microscope.

1. Fairín, A., A. Peters and J. Saldanha 1977 A new procedure for examining Golgi impregnated neurons by light and electron microscopy. J. Neurocytol. 6: 311-337.
2. McNally, K.J. and Peters, A. 1998 A new method for intense staining of myelin. J. Histochem. Cytochem. 46 : 541 – 545.

People

Apart from the personnel listed below, currently Dr. Peters lab has no full time grad students or post-docs. The lab does host grad students from other labs who are interested in learning and applying electron microscopic techniques to support their theses.

Alan Peters, Ph.D
Since retiring from the position of Chairman of the Department in 1998, Alan Peters is now doing full time research into the effects of normal aging on cerebral cortex.

Claire Sethares, Neuroscience Technologist
With the lab since 1986, Claire provides technical assistance and manages the lab.

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Contact Information:

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Department of Anatomy & Neurobiology
Boston University School of Medicine
72 East Concord St (L 1004)
Boston, Massachusetts 02118
Phone 617-638-4200
Fax 617-638-4216
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