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

cortex no t onl y assum e th e functiona l propertie s an d
arrangement o f neurons i n th e visua l corte x but als o
are capabl e o f mediatin g visuall y guide d behavio r
(von Melchner et al, 2000).
Hence, intrinsi c factors suc h a s gen e expressio n
and extrinsi c factor s suc h a s induction , neuron -
neuron interactions , and patterne d activit y are all capable
of regulating cell fate at various (and sometimes
overlapping) point s i n development . No t al l of thes e
mechanisms ar e necessaril y invoke d o r eve n neces -
sary during the production o f any given neuron .
Postnatal Development and
Critical Period s
Critical periods ar e tim e window s i n postnata l de -
velopment durin g whic h neuron s an d circuitr y ar e
particularly receptive to acquiring certain kinds of information
critica l fo r normal developmen t (Hensch ,
2004). Critica l period s hav e bee n extensivel y doc -
umented fo r sensor y systems , moto r systems , an d
multimodal function s suc h a s imprinting , birdson g
learning, soun d localization , an d huma n languag e
learning. How are critical periods useful fo r ensuring
normal development, when i t seems that the unlucky
absence of a particular experience at a particular time
might permanently derail normal development? Th e
answer i s that the critical-perio d onset , duration, and
termination are not regulated simpl y by age, but rathe r
by experience. I f appropriate neura l activatio n i s not
provided at all, then developing circuit s often remai n
in a waiting state until such input is available. For instance,
the segregation of ocular dominance column s
depends o n visual experience. If all visual experience
is denied, the representatio n of the tw o eyes does no t
begin it s segregation an d th e specia l neurotransmit -
ters an d receptor s that ar e responsibl e fo r this structural
chang e ar e hel d i n their initia l state (Kirkwoo d
et al., 1995) . Within certai n constraints , whe n experi -
ence i s reinstated, anatomical , pharmacological , an d
physiological event s then progress as they would have
independent of the ag e of the animals. A similar phenomenon
ha s als o been observe d i n bird s that learn
their songs from tutors—fo r the unfortunate nestlings
born to o late i n th e seaso n t o hear an y of the spring
songs that establish territory, the critical period is held
over unti l nex t spring , whe n singin g begin s agai n
(Doupe an d Kuhl , 1999) . Critica l period s hav e vul -
nerabilities. If activation i s only partial, i t may initiate
the progressio n o f the critica l period , stabilizin g a n
DEVELOPMENTAL DISORDERS AND EVOLUTIONARY EXPECTATIONS 11 5
abnormal state , as has been seen i n the production of
ocular dominanc e columns : i f both eye s ar e closed ,
the critica l period i s delayed. O n th e othe r hand , if
just on e ey e i s closed , th e critica l period proceeds ,
dedicating al l resource s t o th e ope n ey e (Kat z an d
Shatz, 1996) .
ETHANOL AND THE DEVELOPING
NERVOUS SYSTEM:
EVOLUTIONARY CONSIDERATIONS
Here we look at a few of the cases in which the effect s of
ethanol o n developin g system s have been investigated
and consider them in the context of self-regulation. The
effects o f ethanol o n th e nervou s system—at any stage
of development—are known to be numerou s an d varied
(se e Chapter s 11-18) . Fo r instance , ethano l ca n
both inhibi t an d stimulat e neuro n proliferation , de -
pending o n th e physica l locatio n o f the cells , an d th e
concentration an d eve n timin g (da y or night) o f expo -
sure (Luo and Miller, 1998; see Chapter 11) .
Given tha t the effect s o f ethanol o n th e develop -
ing nervous system are numerous, complex, and con -
tingent upo n man y factors , ca n w e b e sur e tha t al l
these effect s ar e malignant? To be sure, some ar e un -
ambiguously deleterious . Ethano l ca n induc e neu -
ronal deat h i n vitro and i n vivo, oxidative stress, an d
excitotoxicity (Chapter s 1 5 an d 16) ; interfer e wit h
glucose transpor t an d uptake; an d reduce th e expres -
sion an d adhesiv e propertie s o f cell adhesio n mole -
cules (Chapter 13) . Other effects of ethanol, however,
may no t necessaril y be maladaptive . Fo r instance, i n
addition t o causin g neurona l deat h i n developin g
cerebellum (L i et al. , 2002 ) and corte x (Jacob s an d
Miller, 2001) , ethano l ca n slo w th e productio n o f
developing cerebella r (L i e t al. , 2002 ) an d cortica l
(Miller an d Nowakowski , 1991 ; Miller , 2003 ) neu -
rons, and it can increase th e time during which post -
mitotic cortica l neuron s remai n i n th e proliferativ e
zone before commencin g thei r migratio n whil e als o
decreasing th e rat e o f neurona l migratio n (Miller ,
1993). Give n tha t developmen t i s dynamically regulated
an d sensitiv e t o environmenta l cues , i t i s no t
implausible that these delays might be an adaptive response
to a hostile developmenta l environmen t (hig h
concentrations o f ethanol) i n whic h cel l productio n
and migratio n ar e retarded unti l a more favorable environment
becomes available. This interpretation gen -
erates testable predictions . I f cell-cycle an d migratio n