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natal weeks of development (Burgard and Hablitz,
1993), and synaptic potentials in the rat hippocampus
display a similar schedule of maturation. Even
synapses in the brainstem display marked alterations
during postnatal development. In the lateral superior
olive, the maximum duration of both glutamatergic
EPSPs and glycinergic inhibitory postsynaptic poten-
tials (IPSPs) declines approximately 10-fold during
the first three postnatal weeks (Sanes, 1993). The
reduction in IPSP and EPSP duration has a similar rate
of development, suggesting that some of the underly-
ing mechanisms are the same. These long-lasting
synaptic potentials probably limit the behavior capa-
bilities of young animals (see Chapter 10).
Why are synaptic potentials of such long duration
in developing neurons? One common difference is that
young synapses usually express a unique form of the
neurotransmitter receptor, called a neonatal isoform .
These transiently expressed receptors often have dif-
ferent functional properties than the receptor that is
expressed by adult neurons. In particular, the receptor-
coupled ion channels in young cells tend to remain
open for a longer period of time, compared to those in
mature cells. In mammalian muscle cells, recordings
were made from single channels with the patch-clamp
recording technique (see BOX: Biophysics: Nuts and
Bolts of Functional Maturation), and the mean channel
open time was found to decline from about 6 to 1 ms
during development (Siegelbaum et al., 1984; Vicini
and Schuetze, 1985). This functional change is due, in
part, to the molecular composition of AChRs in neon-
tates (g-subunit) versus that of adults (e-subunit)
(Figure 8.27A).
Even though nerve cells limp along on one nucleus
in their soma, it appears that they are able to respond
to innervation by altering the receptor isoform expres-
sion. When chick sympathetic ganglion neurons are
innervated, their sensitivity to ACh is enhanced, and
this is correlated with increased expression of 5 AChR
transcripts (Moss and Role, 1993; Corriveau and Berg,
1993). At E11, only 30% of neurons have significant
AChR activity, and each individual patch of membrane
contains a mixture of AChRs. At E17, the great major-
ity of patches have a single functional type receptor.
Similar changes in specific AChR subunits have been
observed in rat brainstem, spinal cord, and dorsal
route ganglia during prenatal development.
A developmental switch in receptor subunits has
now been demonstrated in nearly every transmitter
system in the central nervous system. For example, the
adult form of the glycine receptor heteromer involves
the substitution of a 48 kD ligand-binding subunit for
a neonatal isoform (Becker et al., 1988). Recordings
from rat dorsal spinal cord neurons during develop-
ment showed that there is a complementary change in
function (Takahashi et al, 1992). The glycine-gated
channels from young animals (<P5) open for a much
longer period of time and pass a greater amount of
current, compared to older postnatal animals (Figure
8.29). By examining the properties of two different
glycine receptor subunits in a Xenopus expression
system, it was determined that a transition from the a2
to the a1 subunit could explain the functional change.
When a receptor family has many subunits, the type
of receptor that is produced becomes a combinatorial
problem. The temporal and regional expression of 13
different GABA A receptor subunits in the developing
rat brain provides an interesting example (Laurie et al.,
1992). The expression patterns are determined by in
situ hybridization, a technique in which radiolabeled
antisense oligonucleotides are used as probes for each
species of mRNA (Figure 8.30). The onset of expression
and the adult level of expression can vary greatly for
a single subunit, depending on location. Moreover,
there are a large number of subunits that are tran-
siently expressed within a given structure. As one of
many examples, the onset of g2 subunit expression
occurs throughout the brain at embryonic day 17.
A Young
Long open times, large currents
a 2
B Adult
Short open times, small currents
a 1
FIGURE 8.29 Neonatal glycine receptors have immature func-
tional properties. A. In neonatal mammalian neurons, the glycine
receptor is composed of b and a 2 subunits. When bound by glycine,
the receptors remain open for a relatively long time and pass a rel-
atively large current. B. In adult neurons, the glycine receptor con-
tains a b subunit, but the neonatal isoform, a 2 , is replaced by the a 1
subunit. These receptors open briefly and pass less current than the
neonatal form. (Adapted from Takahashi et al., 1992)
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