Page 102 - ACHEMS 2012 PROGRAM

#P224 POSTER SESSION VI:
OLFACTION CNS; TASTE PERIPHERY &
CNS; MULTIMODAL RECEPTION
Rehabilitation of Olfactory Function Despite Persistent
Olfactory Nerve Pathophysiology in a Mouse Model of
Cadmium-Induced Neurotoxicity
Lindsey A. Czarnecki1, Andrew H. Moberly1, Daniel J. Turkel1,
Tom Rubinstein1, Jospeh Pottackal1, Michelle C. Rosenthal1,
Elizabeth F.K. McCandlish2, Brian Buckley2, John P. McGann1
1Rutgers University, Psychology Department Piscataway, NJ, USA,
2Rutgers University, Environmental and Occupational Health
Sciences Institute Piscataway, NJ, USA
Exposure to aerosols of the heavy metal cadmium has been linked
to olfactory dysfunction including anosmia, hyposmia and
parosmia in humans. However, behavioral studies of olfactory
function following Cd exposure in rodent models have produced
mixed results. Here we a) investigate the pathophysiological,
histopathological, and sensory consequences of intranasal cadmium
exposure for four weeks following acute exposure and b) evaluate a
model of sensory training for rehabilitating the observed olfactory
impairments. Using in vivo optical imaging in transgenic mice
expressing the fluorescent exocytosis indicator synaptopHluorin in
olfactory receptor neuron terminals (Bozza et al., 2004), we found
that acute intranasal Cd exposure greatly suppresses odorant-
evoked neurotransmitter release from the olfactory nerve compared
to vehicle controls, and this effect persists for at least 4
weeks. Throughout this time, Cd levels remain elevated in the
olfactory bulb (measured using mass spectrometry), and there is a
gradual reduction in ORN axonal projection density
to the olfactory bulb. In mice trained to perform a go/no go
olfactory detection task, Cd-exposure drops performance to chance.
Remarkably, two weeks of additional explicit training in the
detection task was sufficient to recover behavioral performance to
baseline levels in all mice. However, optical imaging in
rehabilitated mice revealed that this training did not induce any
restoration of olfactory nerve physiology, suggesting that the
recovery of sensory function reflects a learned reinterpretation of
degraded sensory input in downstream brain regions. These results
demonstrate that sensory learning can mask severe underlying
pathophysiology, but also suggests that rehabilitation training may
rescue toxicant-induced olfactory deficits. Acknowledgements:
This work was supported by the National Institute on Deafness and
Other Communication Disorders, grant number R00 DC009442 to
JPM as well as a grant from the Busch Biomedical Research
Program to JPM.
#P225 POSTER SESSION VI:
OLFACTION CNS; TASTE PERIPHERY &
CNS; MULTIMODAL RECEPTION
Mouse Strain effects on the distribution of glomeruli
throughout the glomerular layer
Ernesto Salcedo, Kyle Hanson, Xuan Ly, Diego Restrep
University of Colorado School of Medicine Aurora, CO, USA
The surface of the main olfactory bulb (MOB) represents a massive
convergence of olfactory information. In mice, axons from ten
million olfactory sensory neurons (OSN), distributed
pseudorandomly in the olfactory epithelium, are sorted into ~1800
spherical neuropil called glomeruli. Due to the topographic patterns
of activation seen in this layer during olfactory perception, the
glomerular layer is thought to contain an odor map important for
encoding olfactory information. Despite intense scrutiny, we still
do not fully understand the complete addressing mechanism that
allows for the precise wiring of the sensory neurons to their
destined glomerulus in the MOB. Nor do we understand the full
implication of the topographic organization of glomeruli as it
relates to odor coding and, ultimately, olfactory-driven behavior.
We have recently shown that environmental factors play a role in
the proper formation and maintenance of semiochemically-
responsive glomeruli. In this study, we have fully characterized
glomerular metrics throughout the MOBs of two strains of mice,
C57Bl6 and SVJ129, raised in identical housing conditions. In both
strains of animals, we find roughly the same number of glomeruli
asymmetrical distributed in both size and number throughout the
glomerular layer, where the highest density and largest glomeruli
are found primarily in the ventral regions of the bulb. Interestingly,
however these asymmetrical distributions differ significantly
between the two strains. This work suggests that strain of the
animal has a subtle, but significant effect on the size and
distribution of glomeruli throughout the surface of the MOB.
Acknowledgements: NIDCD
#P226 POSTER SESSION VI:
OLFACTION CNS; TASTE PERIPHERY &
CNS; MULTIMODAL RECEPTION
Adult-born Interneurons are Necessary for Intrabulbar
Map Refinement
Diana M. Cummings1, Jason S. Snyder2, Heather A. Cameron2,
Leonardo Belluscio 1
1NINDS/Developmental Neural Plasticity Section Bethesda, MD,
USA, 2NIMH/Mood and Anxiety Disorders Program Bethesda,
MD, USA
The olfactory system is unique in that organizational maps persist
in spite of ongoing replacement of sensory and interneuron
populations. Superficial tufted cells receive input from glomeruli
on one side of the olfactory bulb and send their axons to discrete
locations on the opposite side of the same bulb, producing an
intrabulbar map. These projections connect isofunctional odor
columns within the olfactory bulb and are activity dependent such
that they broaden in response to sensory deprivation and gradually
re-refine once afferent activity is restored. We tested the hypothesis
that newly generated interneurons play a role in intrabulbar map
plasticity. We conducted experiments using transgenic mice
expressing the herpes simplex virus thymidine kinase under the
control of either the glial fibrillary acidic protein (GFAP) promoter
(GFAP-TK) or the nestin promoter (Nestin-TK). When GFAP-TK
or Nestin-TK mice are given the antiviral agent ganciclovir (GCV),
stem cells expressing these markers are selectively killed as they
divide, thus eliminating most adult born interneurons. We first
induced a period of sensory deprivation in GFAP-TK and Nestin-
TK mice and used targeted tracer injections to observe the
characteristic broadening of intrabulbar projections. We then
treated with GCV for the following 8 week “recovery” period and
compared the intrabulbar maps in TK and wild type mice. We
found that all wild type mice that underwent deprivation exhibited
normal recovery. In contrast, sensory deprived GFAP-TK and
Nestin-TK mice treated with GCV during the recovery period were
unable to re-refine their intrabulbar projections and exhibited
reduced map specificity. Therefore, we conclude that
adult-born neurons play an integral role in intrabulbar map
plasticity. Acknowledgements: NIH Intramural Program
1ZIANS003002-09 (Belluscio), 1ZIAMH002784-10 (Cameron),
and K01 Award (Cummings)
102 | AChemS Abstracts 2012 Abstracts are printed as submitted by the author(s)
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