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(OECs), an olfactory-specific glial cell. OECs wrap around OSN
axons as they exit the epithelium and enter the bulb. The
mechanisms by which OECs support regeneration are not fully
understood. Intriguingly, OECs express proteolipid protein (PLP),
a myelin protein, yet OECs do not produce myelin in the olfactory
system. The role of PLP in OEC function has not been explored.
We propose that PLP is important for OEC-mediated support of
OSN regeneration after injury based on the finding that that full
glomerular recovery after injury is impaired in the absence of PLP.
In this study nerve transection was performed on 1 month old
PLP+/Y and PLP-/Y mice. The amount of recovery was evaluated
after 2 weeks. PLP-/Y mice had fewer glomeruli structures on the
injured side than PLP+/Y mice, and those that formed were smaller
and demonstrated lower OMP intensity as compared to PLP+/Y
mice, suggesting deficiencies in the regenerative process as a result
of the loss of PLP. Acknowledgements: University of Colorado
Denver Neuroscience Program Training Grant
#P95
POSTER SESSION III:
OLFACTION DEVELOPMENT & CNS;
HUMAN PSYCHOPHYSICS; TASTE PERIPHERY
High-fat diet or genetically-induced obesity reduces the number
of olfactory sensory neurons and their axonal projections
Nicolas Thiebaud
1
, Melissa C. Johnson
2
, Alana M. Gale
3
,
Debra A. Fadool
1,4
1
The Florida State University, Department of Biological Sciences
Tallahassee, FL, USA,
2
University of West Georgia, Department of
Biology Carrolton, GA, USA,
3
Larry A. Ryle High School Union,
KY, USA,
4
The Florida State University, Programs in Neuroscience
and Molecular Biophysics Tallahassee, FL, USA
The nutritional status of an individual impacts olfactory function as
mediated through a myriad of internal metabolic cues (nutrients,
hormones...) received at the olfactory mucosa (OM) and the
olfactory bulb (OB). Here, we examined the structural effect of a
long-term deregulation of the nutritional status on the development
of the olfactory system. We studied anatomical changes in two
models of obese mice 1) a diet-induced obesity where mice were
maintained for 6 months on a moderately high-fat diet (MHF, 32%
fat) and 2) a late-onset obesity in melanocortin 4 receptor null mice
(MC4R-/-) where diabetes secondarily precipitates following
disruption of the hypothalamic axis. M72-receptor β-gal positive
(M72+) olfactory sensory neurons (OSNs) and the total number of
mature, OMP+ OSNs were significantly decreased following the
MHF-diet. The reduction in the axonal projections of M72+ OSNs
lead to a decrease in the size of the corresponding glomeruli.
These effects were more moderate in the MC4R-/- genetically-
obese mice. MHF-fed mice also exhibited an increase in
proliferation (α-Ki67) and apoptotic (α-activated-caspase 3 and
TUNEL) markers at the OM level. We also investigated the effect
of Kv1.3 potassium channel deletion (Kv1.3-/-) in mice which,
besides a “Super-smeller” phenotype, are resistant to adiposity
and weight gain upon MHF-diet challenge. Although Kv1.3-/- mice
did not gain weight and remained euglycemic, thin body plan failed
to prevent the loss in the number of M72+ OSNs and the reduced
glomerular size associated with the MHF diet. Our results suggest
that a diet high in fat durably affects the neuroanatomy of the
olfactory system independent of body weight. Furthermore, the
increased proliferation and apoptosis of OSNs suggests a
mechanism attributed to chronic inflammation.
Acknowledgements: This work was supported by R01 DC003387
and ARRA DC003387-SUMM from the NIH/NIDCD.
#P96
POSTER SESSION III:
OLFACTION DEVELOPMENT & CNS;
HUMAN PSYCHOPHYSICS; TASTE PERIPHERY
Wnt5
AND
DRL
REGULATE DENDRITIC TARGETING IN
DROSOPHILA OLFACTORY MAP FORMATION
Huey Hing
1
, Yuping Wu
2
, Jasprina Noordermeer
3
, Lee Fradkin
3
1
SUNY Brockportport/Biology Brockport, NY, USA,
2
Stowers
Institute Kansas City, KS, USA,
3
Leiden University Medical Center
Leiden Netherlands
In the development of the
Drosophila
antennal lobes, targeting
of the projection neuron (PN) dendrites is alone sufficient to create
the nascent olfactory map. The mechanisms regulating PN
dendrites targeting are poorly understood. We observed that the
secreted protein, Wnt5, and its receptor, Drl, are required for this
process. Loss-of-function mutations of the
Wnt5
and
Drl
genes
result in distinct dendritic targeting defects. Interestingly, the
Drl
mutant defects could be rescued by the removal of a copy of the
Wnt5
gene, indicating that
Wnt5
and
Drl
act antagonistically. To
investigate how Wnt5 and Drl regulate PN dendrites targeting, we
examine the relative distribution of the two proteins in the nascent
antennal lobe. We show that Wnt5 is expressed in discrete domains,
each of which spans only a few glomerular boundaries. Drl
expression is also tightly controlled, with adjacent dendritic arbors
expressing different levels of the protein. Comparison of the Wnt5
and Drl expression patterns showed that Drl+ arbors are located
inside, while Drl- arbors are located outside of the Wnt5 domains,
suggesting that Drl modulates dendritic responses to Wnt5. We
propose that Drl+ dendrites are attracted to, while Drl- dendrites are
repelled by Wnt5. Wnt5 may thus act as a local organizer of the PN
dendrites, thereby elaborating the rough dendritic map of the
nascent antennal lobe. Our findings begin to define the molecular
and cellular mechanisms that guide PN dendrites movement and
pattern the early olfactory map. Acknowledgements: NIH/NIDCD
1R15DC010916
#P97
POSTER SESSION III:
OLFACTION DEVELOPMENT & CNS;
HUMAN PSYCHOPHYSICS; TASTE PERIPHERY
How many colors do you need to paint an olfactory map?
Alexei Koulakov, Brian Kolterman, Toma Marinov
Cold Spring Harbor Laboratory Cold Spring Harbor, NY, USA
Olfactory sensory neurons (OSN) expressing a particular olfactory
receptor selectively project their axons to a particular subset of
glomeruli in the olfactory bulb (OB). The resulting olfactory map
yields robust odorant- specific activation patterns of the glomeruli.
A well understood example of a neural map is the continuous
topographic projection of the retinal ganglion cells to the superior
colliculus in the visual system. It has been demonstrated that this
retinotopic map is a result of a combination of axonal guidance due
to global gradients of chemoattractants/chemorepellents and a local
map refinement due to correlated neural activity. We study the
computational model of the olfactory map formation that is similar
to the models of visual map development. We simulate the
projection of the OSNs from a receptotopic space to the surface of
the OB, similarly to the retinotopic projection to the superior
colliculus. The role of the global molecular labels is played by the
gradients of axon guidance molecules (Slit1/Robo2, Nrp1/Sema3A,
Nrp2/Sema3F). The local activity-dependent refinement is
implemented via discrete mosaic levels of OR-specific molecules
(EphA/ephrin-A, Kir2/Kir3, Big2). The OSN axons are arranged in
the receptotopic space according to Nrp1 and Nrp2 levels, which is
Abstracts | 59
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