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Appendix D:

Approaches to Explore

the Brain

Morphological studies

Gross dissection of the brain provided classical information on brain parts.

Histology: Light microscopic examination of brain sections coupled

with various staining procedures provides basic information at the cellular

level. A classic example consists of the Golgi staining method (based on

silver), which provided crucial information on neuronal connections,

giving rise to the “neuron doctrine,” the cornerstone of neuroscience.

Histo-chemistry: Microscopic examination of brain sections or

cultured brain cells using enzyme reagents, antibodies, polynucleotide

probes, coupled with radioactivity or fluorescent reagents, provides chem-

ical information on the cellular and subcellular makeup of brain tissue.

Confocal microscopy provides information on various depths of

the brain tissue. It is particularly powerful when combined with fluores-

cence microscopy.

Transmission electron microscopy (TEM), or simply electron

microscopy (EM), visualizes subcellular structures down to the macro-

molecular level, including the organization of the synaptic junction and

the presence of synaptic vesicles that contain neurotransmitters.

Scanning electron microscopy (SEM) reveals surface structures

of isolated brain cells or serial brain sections.

Chemical/pharmacological studies

Chemical analysis identifies the molecules (neurotransmitters) respon-

sible for message transmission across the synapse. Molecules that affect

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