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hypothalamus, it has been found that some protocad-
herins are found just at excitatory synapses (Phillips et
al., 2003). Of course, these molecules are likely to do
more than simply glue particular synapses together;
they are also likely to be involved in the maturation,
structural organization, and stabilization of synapses,
topics that will be covered in more detail in Chapter 8.
A
B
6
6
7
7
Wild type
Increase in FAS II on
muscle 6 only
TN
RP3
TN
RP3
SNIFFING OUT TARGETS
C
D
6
6
6
6
The way that the axons of olfactory receptor neurons
find their particular targets in the olfactory bulb of the
vertebrate brain has proven to be an extraordinary case
of cell-specific targeting. Olfactory receptors are located
in the olfactory sensory epithelium of the nose, and they
send axons into the bulb where they make connections
with second-order cells in synaptic complexes called
glomeruli . Physiological studies reveal that distinct
odorants cause activity in distinct glomeruli, and in the
zebrafish, a careful anatomical study showed a repro-
ducible pattern of about 80 glomeruli that have the
same position and size from individual to individual
(Baier and Korsching, 1994). Surprisingly, the receptors
projecting to a single glomerulus are scattered all over
the olfactory epithelium in a fairly random pattern, and
there is no regionalization of odorant receptors on the
sensory epithelium (Figure 6.25). So point-to-point
mapping does not occur as it does in the visual or
somatosensory systems. In the mammalian olfactory
epithelium, about 1000 different genes code for the
seven transmembrane receptors to odorants (Buck and
Axel, 1991). By using in situ hybridization, it is possible
to label all the olfactory sensory cells that express a
particular receptor molecule. Odorant receptor genes
are expressed in nonoverlapping subsets of sensory
neurons, each neuron expressing only one of the 1000
odorant receptor genes. All the sensory neurons that
express a particular odorant receptor are located within
one of four zones, and neurons in each of these zones
send axons to the glomeruli situated in matching zones
of the olfactory bulb. So there is some topography, but
again surprisingly within each zone, all the receptors
that express a particular odorant receptor gene are dis-
persed widely and randomly throughout the zone, so
there is no spatial topography with the zones. The
amazing thing is that all the olfactory neurons that
express the same olfactory receptor genes, though dis-
tributed over a wide area of the olfactory epithelium,
nevertheless project their axons to single glomeruli
in specific regions of the olfactory bulb (Vassar et al.,
1994). And although there are more than 2500 choices
of glomeruli, the olfactory neurons that express the
7
7
7
7
TN
TN
TN
TN
Increase of NET or FAS II
or Decrease of SEMA II
Increase in NET or FAS II
plus increase in SEMA II
E
F
6
6
6
6
7
7
7
7
RP3
RP3
RP3
RP3
Decrease in NET
or increase in SEMA II
Increase in NET and SEMA II
or decrease in SEMA II and NET
FIGURE 6.24 Combinatorial coding of targeting at a single-cell
level. A. In wild-type Drosophila larva, the TN nerve does not inner-
vate muscle fibers 6 and 7, whereas the RP3 nerve innervates
both. B. When FasII is increased on muscle 6 only, both the TN nerve
and the RP3 nerve innervate this muscle differentially. C. When
Netrin expression or FasII expression is increased on both muscles,
or when SemaII is decreased on both, the TN nerve innervates both
6 and 7. D. When Netrin or FasII is increased but SemaII is also
increased simultaneously, then the TN nerve does not innervate 6
and 7. E. When there is a decrease in Netrin or an increase SemaII,
the RP3 nerve does not innervate muscles 6 and 7. F. However, when
there is either an increase or a decrease in both SemaII and Netrin,
the RP3 nerve innervates as normal. (Adapted from Winberg et al.,
1998)
Sdks and Sygs discussed above, are involved in a
synaptic targeting code (Redies and Takeichi, 1996). As
an example of how this might work, consider the N-
and E-cadherins, which are distributed at synaptic
junctions in a mutually exclusive pattern along the
dendritic shafts of single pyramidal neurons (Fannon
and Colman, 1996). Ultrastructural examination of
double immunolabeled material revealed the existence
of many unlabeled synapses on these cells as well as
raising the possibility that synapses at these other
synapses are linked by other cadherins or CAMs. In the
 
 
 
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