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A Normal P2 projection
postnatally such that eventually each glomerulus is
innervated by only a single receptor type (Zou et al.,
2004). The importance of successful physiological activ-
ity in mapping is also supported by experiments
showing that inhibition of all spontaneous activity in a
subset of olfactory sensory neurons that express a single
odorant receptor causes a selective unraveling of the
target glomerulus, with the axons that originally
invaded this glomerulus now making inappropriate
contacts in various regions of the bulb (Yu et al., 2004).
There is a suggestion that activity is important for the
continued expression of particular odorant receptors.
Therefore, physiologically ineffective olfactory neurons,
like those just mentioned, may express other receptors
and cause the axons of these cells to begin to wander the
bulb in an attempt to innervate other glomeruli.
Insects have olfactory sensory neurons in their
antennae, and these also send axons into olfactory
glomeruli in the brain, according to a “one receptor
type one glomerulus” rule. However, in Drosophila,
odorant receptor gene manipulations suggest that,
unlike mammals, the receptor molecules themselves
are not critically involved in targeting. However,
specific olfactory receptor neuron classes require the
cell surface protein Dscam (Down Syndrome Cell
Adhesion Molecule) in order to target to the correct
glomeruli (Hummel et al., 2003). In Dscam mutants,
the axons of these cells often do not find the correct
target glomerulus. Multiple forms of Dscam RNA are
detected in the developing antenna, and Dscam protein
is localized to developing ORN axons. Dscam is an
IgG-superfamily member, and the gene encoding it has
a huge number of potential splice variants. Many of
these variants are expressed differentially in subsets
of neurons, including subsets of olfactory sensory
neurons. Amazingly, there are more than 38,000 iso-
forms of the Dscam protein (Schmucker et al., 2000)
(Figure 6.28), and studies suggest that each isoform
binds homophilically to itself but does not bind to other
isoforms; even closely related isoforms exhibit isoform-
specific homophilic binding (Wojtowicz et al., 2004). It
has not escaped the attention of developmental neuro-
biologists that such diversity could contribute to the
specificity of neuronal connectivity.
Olfactory bulb
P2 olfactory
P2 receptor
Axons converging
on P2 glomerulus
B Receptor deletion
P2 olfactory
with P2
Axons grow into bulb
but fail to converge
C Receptor swap from different zone
M71 glomerulus
M71 P2
P2 olfactory
M71 rec eptor
(M71 P2)
Axons converge at new glomerulus
between M71 and P2 glomerulus
D Receptor swap from same zone
P2 P3
FIGURE 6.27 Olfactory receptors are involved in central target-
ing. A. Axons from olfactory neurons expressing the P2 receptor
converge on the P2 glomerulus. B. If the P2 receptor is deleted, these
axons do not converge on any glomerulus. C. If these neurons are
made to express the M71 receptor instead of the P2 receptor, they
converge on a glomerulus somewhere in-between P2 and M71. D. If
they are forced to express the P3 receptor and the P3 glomerulus is
in the same zone as the P2 glomerulus, they converge on a glomeru-
lus right next to P3. (After Mombaerts, 1996; Wang et al., 1998)
P2 olfactory
P3 r ec eptor
(P3 P2)
Axons converge on
new glomerulus right next
to P3 glomerulus
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