Brain Development: Normal Processes and the Effects of Alcohol ...

184 ETHANOL-AFFECTE D DEVELOPMENT
ontogenetic column i s a hypothetical uni t of developing
cortex that includes the proliferative cells and the
radial array of the progen y (e.g. , Rakic, 1978, 2000).
This conclusion i s supported b y data showing that the
density o f radia l glia l fiber s (th e guides commonl y
used t o coordinate neurona l migration ) is unaffected
by prenatal exposur e t o ethanol (Mille r and Robert -
son, 1993).
Finally, th e inside-ou t sequence i s largely maintained
until the end of cortical neurona l generation .
At this time , man y neuron s destine d fo r superficial
cortex en d u p i n deep corte x because o f a defect in
neuronal migratio n (se e Chapter 13) . The effect s o f
ethanol o n neuronal generation may be best appreciated
b y tracing the ontogen y of select populations of
cortical neurons , fo r example, corticospinal (Miller ,
1987) an d callosa l projectio n (Miller , 1997 ) neu -
rons. In general, they are distributed in laminae that
are normal for their phenotype, with the notabl e exception
o f the late-generated callosa l neurons. Many
of thes e neuron s resid e i n infragranula r laminae .
Thus, in addition to the conclusions described above,
it appears that (a) ethanol doe s not affect the connectional
phenotype of a particular neuron (regardles s of
a migratio n defect) and (b ) the decisio n about neuronal
lineag e occur s a t the tim e o f neuronal origin .
Similar cortica l disorganizatio n o f neurona l pheno -
types occur s i n cortice s in whic h cell s i n th e proliferative
zone s ar e heterochronicall y transplante d
(McConnell, 1988) .
Sites o f Proliferation . Th e proliferatio n o f neuronal
precursor s occur s i n specifi c site s generall y
located proxima l t o th e ventricula r syste m (se e
Chapter 2) . For neocortex, cell proliferation occurs in
three sites (Fig. 11-2). The ventricula r zone (VZ) is a
pseudostratified epitheliu m linin g th e latera l ventri -
cles (Sauer , 1936 ; Watterso n e t al., 1956 ; Saue r an d
Chittenden, 1959 ; Jacobson, 1991) . The subventricu -
lar zone (SZ ) is a stratified epitheliu m externa l to the
neocortical V Z (Ramo n y Cajal , 1909-1911 ; Rakic
et al, 1974 ; Shoukimas and Hinds, 1978) . Th e ganglionic
eminenc e (GE ) generates som e loca l circui t
neurons (Tamamaki et al, 1997 ; Zhu et al, 1999 ; Anderson
étal, 2001; Wichterle étal, 2001).
The tw o primary neocortical proliferatio n zone s
are th e V Z an d SZ , an d ther e i s some controvers y
about the contribution of the VZ and S Z in the generation
o f neocortica l neurons . Som e investigator s
FIGURE 11- 2 Effect s o f ethanol o n the thre e sources
of neocortica l neurons . Neuron s tha t populat e th e
cortical plat e (CP ) are derive d from th e ventricular
zone (VZ) , subventricular zone (SZ) , and ganglioni c
eminence (GE) . In norma l rats , V Z an d S Z cell s
principally giv e rise to infra - an d supragranula r neurons,
respectively (solid lines). The G E generate s local
circui t neuron s tha t ar e distribute d throughou t
neocortex. Followin g prenata l exposur e t o ethanol ,
many late-generate d neuron s (originatin g largely in
the SZ ) complet e thei r migration s i n dee p corte x
(dashed line) . IZ, intermediat e zone ; MZ , marginal
argue that the V Z i s the sit e o f neuronal origi n an d
that th e S Z generate s gli a an d glia l precursor s
(Gomes et al, 2003 ; Samuelson et al, 2003) . In contrast,
other s argu e tha t al l neuron s ar e derive d fro m
the S Z and that the VZ is merely a self-replacing population
(Doetsc h e t al , 1997 , 1999; Alvarez-Buylla
and Garcia-Verdugo , 2002 ; Marten s e t al , 2000 ,
2002). Other studies support a different mode l o f cortical
development, that both th e VZ and S Z give rise
to cortica l neuron s (Miller , 1992 ; Luo an d Miller ,
1998).
Studies on th e consequence s o f prenatal exposure
to moderate amounts of ethanol (sufficien t to produce