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#37
SYMPOSIUM: WIRING NEURAL CIRCUITS
IN OLFACTORY SYSTEMS
Developmental Regulation of Neural Circuit Formation in the
Mouse Olfactory System
Hitoshi Sakano
Department of Biophysics & Biochemistry, Graduate School of
Science, University of Tokyo Tokyo, Japan
In the mouse olfactory system, much of axon wiring in neural map
formation occurs autonomously by axon-axon interactions of
olfactory sensory neurons (OSNs). Axonal projection along the
dorsal-ventral (D-V) axis is regulated by positional information of
OSNs within the olfactory epithelium (OE). Unlike the projection
along the D-V axis, anterior-posterior (A-P) projection is instructed
by OR molecules that regulate the expression levels of axon
guidance molecules using cAMP as a second messenger. Many
G-protein coupled receptors are known to have two conformations,
active and inactive, and spontaneously transit between the two,
generating the basal activity in the absence of agonists. We assume
that the OR-derived basal activity participates in the olfactory map
formation. Beta2-adrenergic receptor (beta2-AR) is known to share
many functional similarities with OR molecules and substitute ORs
for OR-instructed OSN projection. Taking advantage of these
previous observations, we have analyzed axonal projection of
OSNs instructed by the mutant-type beta2-AR with the altered
levels of basal activity. We have found that the basal activity
mutants of beta2-AR alter expression levels of axon guidance
molecules, e.g., Nrp1 and Sema3A, and change glomerular
locations along the A-P axis in the OB. After establishing the
topographic map of glomeruli, the map needs to be properly
connected with second-order neurons, mitral/tufted (M/T) cells.
We have found that Sema3F, a repulsive ligand to Nrp2, which is
secreted by early-arriving dorsal OSN axons, guides both late-
arriving Nrp2
+
OSN axons and their partner Nrp2
+
M/T cells to the
ventral region of the OB. This coordinated guidance is an important
process for proper alignment and synapse formation of OSN axons
and M/T cells during olfactory development. Acknowledgements:
Specially promoted grant from the Japanese Government
#38
SYMPOSIUM: WIRING NEURAL CIRCUITS
IN OLFACTORY SYSTEMS
Olfactory sensory axons target specific identified
protoglomeruli in the zebrafish
Jonathan A. Raper
University of Pennsylvania School of Medicine, Dept. of
Neuroscience Philadelphia, PA, USA
The zebrafish is an almost ideal system in which to study the
initial targeting of olfactory sensory axons within the olfactory
bulb. It is relatively simple, develops very quickly, and is accessible
to observation and manipulation at all stages of development.
Importantly, the initial targets of sensory axons in the olfactory
bulb are distinct, individually identifiable protoglomeruli, making it
possible to access the specificity of early targeting. We have
mapped the projections of two broad classes of olfactory sensory
neurons that target mutually exclusive protoglomeruli. OMP
expressing sensory axons project to the Central Zone, Dorsal Zone,
MG, and LG3 protoglomeruli. TRPC expressing axons project to
the Olfactory Plexus, VP, LG1, LG2, and LG4 protoglomeruli. We
have engineered transgenic fish lines in which the expression of a
particular odorant receptor is linked to the expression of an axonal
tracer. In the first line we produced, a minigene construct drives
expression of the odorant receptor OR111-7 and a tracer.
Depending on the developmental age, approximately 5-25
fluorescently labeled olfactory sensory neurons are observed in
each olfactory pit. At 3 dpf, their axons project predominantly to
the Central Zone protoglomerulus while a much smaller number of
axons sometimes project to the LG1 protoglomerulus. The high
specificity of this projection allows us to determine the
contributions of candidate guidance cues on olfactory guidance in
mutant embryos or with morpholino knockdown experiments.
Using this approach, we have found that netrins 1a and 1b
expressed at the ventral and midline margins of the bulb act as
attractants that draw the axons of OR111-7 transgene expressing
sensory neurons into the ventrally and medially positioned Central
Zone protoglomerulus. Acknowledgements: This work was
supported by 9RO1-DA025407 from NIDA
#39
SYMPOSIUM: WIRING NEURAL CIRCUITS
IN OLFACTORY SYSTEMS
Representations of Olfactory Information in Mammalian
Olfactory Cortex
Sandeep R Datta
Harvard Medical School Department of Neurobiology Boston,
MA, USA
Sensory information is transmitted to the brain where it is
processed to translate stimulus features into appropriate behavioral
outputs. In the olfactory system, distributed neural activity in the
nose is converted into a segregated glomerular map in the olfactory
bulb. Here we describe the development and deployment of a
neural tracing technique that enables us to ask how this ordered
representation is transformed in higher centers in mouse olfactory
cortex. We use this tracing strategy to characterize the neural
circuits that convey information from defined glomeruli in the
olfactory bulb to the piriform cortex and the cortical amygdala.
We find that the spatial order apparent in the olfactory bulb is
discarded in piriform cortex; axons from individual glomeruli
project diffusely to the piriform cortex without apparent spatial
preference. In contrast, within the cortical amygdala we observe
broad patches of projections that are spatially stereotyped for
individual glomeruli. The identification of a distributive pattern of
projections to the piriform cortex and stereotyped projections to the
cortical amygdala suggests distinct roles for each of these brain
areas in processing olfactory information. Acknowledgements:
NIH Director’s Office DP2OD007109, NIH NIDCD
RO1DC011558, Burroughs Wellcome Fund, Searle Foundation,
McKnight Foundation, Sloan Foundation.
O R A L A B S T R A C T S