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

56 NORMA L DEVELOPMENT
stop axon extension or stimulate the generation of terminal
arbors for synapse formation.
SYNAPTOGENESIS
Sherrington coine d th e ter m synapse i n 189 7 t o de -
scribe the site s where axons contact th e dendrite s o r
soma o f other neurons , i n keepin g wit h th e neuro n
doctrine that nervous tissue comprises separat e cells .
Although thi s doctrine also was espoused b y Ramon y
Cajal? Kôlliker , His, Forél, and severa l other contem -
poraries, Golgi and other s fervently supported a n opposing
reticular theory that the nervous system was an
anastomosing network (Shepherd, 1991) . Sinc e arguments
fro m bot h side s were base d mostl y o n Golgi -
impregnated sample s viewe d b y ligh t microscopy ,
unequivocal evidence supportin g the former doctrin e
did not come until half a century later from a series of
electrophysiological an d E M studies . Kuffle r (1942 )
and Fat t an d Kat z (1951 ) demonstrate d a t th e fro g
neuromuscular junctio n tha t th e curren t underlyin g
changes i n membran e potentia l a t th e postsynapti c
muscle endplat e coul d no t deriv e directl y fro m th e
presynaptic moto r axon, as the reticular theory would
have predicted . The n studie s b y Palad e an d Pala y
(1954) an d D e Roberti s an d Bennet t (1955 ) i n th e
mid-1950s provided clear, high-resolution EM image s
of a cleft separating pre- and postsynapti c membrane s
at chemica l synapses . Ironically , soli d evidenc e
supporting th e existenc e o f a n electrotoni c synaps e
came shortly thereafter, with the identificatio n o f gap
junctions, wher e Bennet t (1963 ) an d other s demon -
strated tha t ioni c curren t ca n flow directly from on e
neuron t o anothe r (Peter s e t al. , 1991 ; Shepherd ,
1991).
Subsequent electrophysiological , anatomical, and
biochemical findings continu e to challenge our col -
lective notio n o f th e synaps e beyon d Sherrington' s
general conceptualization . Thoug h characterizin g
the matur e synapse in differentiate d neura l networks
has occupied neurobiologist s fo r more than a century,
more recen t wor k indicate s tha t earlie r stages o f assembly
and differentiatio n ar e crucial for generating a
normal network . In thi s vein, the las t sections o f this
chapter describ e ho w axona l and dendriti c morpho -
logies an d compositio n ar e modifie d t o assembl e
synapses i n th e vertebrat e CNS . Sinc e maturatio n is
generally assesse d b y th e exten t t o whic h adul t fea -
tures are present, the following discussion of chemical
and electrica l synapse s begin s wit h description s o f
their mature form and composition .
Structure an d Composition of
Mature Chemical Synapse s
Ultrastructural Features
The matur e chemical synaps e is a polarized, adhesiv e
junction formed most commonly between axon s and
dendrites. In electro n micrograph s thi s synaps e
(sometimes called a zonula adherens) i s characterized
by rigidly parallel pre - and postsynapti c membranes ,
separated b y a clef t o f 1 2 to 2 0 nm, electron-dens e
material withi n th e clef t and , i n most cases , thick ,
electron-dense materia l i n th e cytoso l subjacen t t o
the postsynapti c membran e (Fig . 4-7) . Thi s synapse
resembles othe r adhesive junctions , but can be distinguished
b y th e presenc e o f synapti c vesicle s (SVs )
close to the junction i n the presynaptic cytoso l (Gray ,
1963). I n aldehyde-fixe d E M specimens , SV s ar e
roughly 40-50 nm i n width, can appea r spherica l o r
oblong (pleomorphic) , an d ca n hav e agranula r o r
electron-dense core s (Grill o an d Palay , 1963 ; Val -
divia, 1971) . A t mos t synapse s the y ar e foun d i n a
readily releasable pool near the plasma membrane or
in a more remove d reserv e pool. Vesicle s within thi s
pool ca n b e foun d docke d withi n a gridded arra y of
presynaptic cytomatri x component s or , i n photore -
ceptors, along a presynaptic ribbon that runs orthogonal
t o th e junctio n (Sjostrand , 1958 ; Gray , 1959a ;
Bloom an d Aghajanian , 1966 , 1968) . Mitochondri a
are ofte n foun d both pre - and postsynapticall y (Ibat a
and Otsuka , 1968 ; Bodian , 1971) , an d a postsynapti c
web of filaments is often subjacent to the postsynaptic
density (PSD ) (D e Roberti s e t al, 1961 ; Gray , 1963 ;
Peters an d Kaiserman-Abramof , 1969 ; Stewar d an d
Levy, 1982 ; Space k and Harris , 1997) .
Although dendrodendritic, dendrosomatic, and all
other conceiveable pairing s do occur in the vertebrate
CNS, th e larg e majorit y o f chemica l synapse s
encountered ar e axosomati c o r axodendriti c (Peter s
et al , 1991) . Axodendriti c synapses occur o n eithe r
smooth dendriti c shaft s o r mushroom-shaped protru -
sions calle d spines tha t stu d th e dendriti c arbor s
of most glutamatergi c neuron s (Nimchinsk y e t al ,
2002). Spin e synapse s are typifie d b y a pronounced
PSD, a relativel y wide clef t (nea r 2 0 nm), polyribo -
somes i n clos e proximit y t o smoot h endoplasmi c
reticulum, an d rounde d presynapti c vesicle s i n