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bellar effects. The mature cerebellum is made up of
several distinct cell types, each repeated in an almost
crystalline array (Figure 3.23). The two most distinctive
of these cell types are the giant Purkinje cells and the
very small granule cells. Purkinje cells are the principal
neurons of the cerebellar cortex, sending axons out of
the cortex to the deep cerebellar nuclei. The cerebellar
granule neurons are much more numerous than the
Purkinje cells. In fact, the cerebellar granule cells are
the most numerous type of neuron in the brain. In the
mature cerebellum, they form a layer deep to the Pur-
kinje cells, and their axons extend past the Purkinje cell
layer into the molecular layer. The axons of the granule
cells bifurcate in the molecular layer, into a T-shape,
and these axons extend in the molecular layer for a con-
siderable distance, synapsing on the Purkinje cell den-
drites. One can think of the Purkinje cells as telephone
poles and the granule cell axons as the telephone wires.
The generation of the intricate cerebellar architec-
ture is a complex process. The large Purkinje neurons
are generated from a ventricular zone near the fourth
ventricle of the brainstem, in a manner similar to the
way in which the neurons of the cerebral cortex are
produced (as described in the previous section). Once
they have finished their final mitotic division, the
Purkinje cells migrate a short distance radially to
accumulate as an irregular layer, known as the cere-
bellar plate. As the cerebellum expands, these cells
become aligned to form a single, regularly spaced
layer. The Purkinje cells then grow their elaborate den-
drites. In addition to the Purkinje cells, the ventricular
zone generates several other cerebellar interneurons,
such as the stellate and basket cells.
In contrast to the somewhat standard pattern of
neurogenesis of the Purkinje cells and the stellate and
basket cells, the granule cells arise from a completely
separate progenitor zone, known as the rhombic lip
(Figure 3.24). The granule cell precursors are initially
generated near the rim of the fourth ventricle but then
migrate away from the ventricular zone, over the top
of the developing Purkinje cells to form a secondary
zone of neurogenesis, called the external granule layer .
The cells in this layer continue to actively proliferate,
generating an enormous number of granule cell
progeny, thus increasing the thickness of the external
granule layer considerably. The external granular layer
persists for a considerable time after birth in most
mammals and continues to generate new granule
neurons. There are still granule neurons migrating
from the external granule layer as late as two years
after birth in humans (Jacobson, 1978).
Although the granule neurons are generated super-
ficially in the cerebellar cortex, they come to lie deep to
the Purkinje cells in the mature cerebellum. The devel-
oping granule neurons must therefore migrate past the
FIGURE 3.21 The cells generated by the subventricular zone in
mature rodents migrate to the olfactory bulb in the rostral migratory
stream. The cells migrate in chains, along extended astrocyte net-
works that lie adjacent to the lateral ventricles of the cerebral cortex.
These networks are complex but in general have rostral-caudal
orientation. (From Doetsch and Alvarez-Ruylla, 1996)
neurons of a region of the hippocampus known as the
dentate gyrus originate from the ventricular zone for
relatively short periods of embryonic development in
the rat prior to E14 . These progenitor cells then migrate
to the growing dentate gyrus, and they, too, produce
additional neurons for the rest of embryonic develop-
ment, and even into adult life (see below).
Are radial glial cells also important for the migration
of neurons and progenitors of neurons and progenitors
in the secondary zones of histogenesis? Studies of the
SVZ have been particularly illuminating. After the
initial burst of gliogenesis (see above), most of the cells
generated in the SVZ during the postnatal period and
in mature rodents migrate to the olfactory bulb, in what
is known as the rostral migratory stream (Lois et al.,
1996). The cells migrate in chains, along extended
astrocyte networks. These networks are complex (see
Figure 3.21) but in general have rostral-caudal orienta-
tion. One might imagine that the association of migrat-
ing SVZ cells is analogous to the migration of cortical
neurons along radial glia; however, the SVZ cells do
not appear to require the glia. The migration of SVZ
cells has been termed chain migration and is distinct
from the migration of neurons along radial glia. The
SVZ cells form a chain in vitro, even in cultures devoid
of glial cells, and migrate by sliding along one another.
Figure 3.22 shows this process of leapfrogging SVZ
cells in a time-lapse series. Thus, glia might help to
orient SVZ migration but are not essential for it.
As noted above, the cerebellum is a large, highly
convoluted part of the brain that is critical for control of
our movements, particularly our balance. Cerebellar
function is particularly susceptible to ethanol; the
weaving motion of alcoholics is likely due to the cere-
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