Tool Module: Identifying Pathways in the Brain
To identify the connections between the various structures in the
brain, researchers can work directly with the human brain, but often, they use
animal models instead.
In animal studies,
researchers can use two different types of experimental
techniques, based on the reaction of neurons to lesions
axon is disconnected from the body of its neuron, it degenerates and is eventually
attacked by phagocytic cells. Researchers therefore produce highly localized lesions,
then use dyes to trace certain pathways. This approach is limited, however, because
not all neurons display marked degeneration after a lesion.
Tracing techniques, based on the ability of neurons to transport molecules
through their axons
To locate the origin of a neural pathway, researchers
can inject a molecular marker such as the enzyme horseradish peroxidase into the
region where the axons terminate. This marker is then transported toward the neuronal
cell bodies by a phenomenon known as retrograde axonal transport. Once it reaches
these cell bodies, the marker catalyzes a reaction whose product can be detected
under an electron microscope. Thus the neurons where the pathway originates are
Conversely, researchers can also determine the point where axons
terminate by injecting certain radioactive precursors into the region where the
neuronal cell bodies are located. The cell bodies incorporate these radioactive
precursors into macromolecules, which are then carried to the ends of the axons
by anterograde axonal transport. Radiation-sensitive film is then used to capture
images of the pathways thus marked.
The Emotional Brain, by Joseph LeDoux
Even though the brain contains billions of neurons that form an incredibly
complex network, such tracing techniques can reveal very specific connection patterns.
In the diagram here, for example, the central neural network receives inputs from
regions B and C, but not from regions A and D. This network also sends outputs
to regions X and Y, but not W or Z. Also, region C communicates with region Y
both directly and through the central network.
studying human brains directly, researchers
obviously cannot create lesions or inject markers, so they must use other approaches.
Instead, they take advantage of the fact that after a lesion occurs naturally
in the brain, there are long distances over which the axons do not regenerate.
The space created in the nervous system by the disappearance of these axons becomes
filled with astrocytes that will leave “scars” where the pathways once were. By
observing such tissue changes following very specific types of accidental lesions,
researchers have accumulated reliable data on the connectivity of the human brain.
data, combined with those from animal studies, have given scientists a good idea
of the general connectivity of the brain. They also help us understand why we
do not yet have a complete picture of all the pathways in the brain.