the main question:
DESCRIPTION
The main question: How is the topographical information in the olfactory bulb transmitted to and interpreted in the brain to decode the odor map?. Zone-to-Zone Projection (receptor identity). Zone-to-Zone Projection (zone specific markers + olfactory receptor subtypes). coronal slice. - PowerPoint PPT PresentationTRANSCRIPT
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The main question:
How is the topographical information in the olfactory bulb transmitted to and
interpreted in the brain to decode the odor map?
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Zone-to-Zone Projection
(receptor identity)
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Zone-to-Zone Projection
(zone specific markers + olfactory receptor subtypes)
Class I receptor
Class II receptor
(O-MAC)
(OCAM)
coronal slice
Markers:
O-MAC- olfactory specific medium-chain acyl-CoA synthetase (expressed only in the D-zone). OCAM (NCAM2) - olfactory cell adhesion molecule (expressed only in the V-zone).
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ΔIIΔD
Synaptotagmin GFP OCAM
wt
Receptor expression
Two strains of mice
(specific expression of diphtera toxin)
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ΔD mice
ΔD
Synaptotagmin GFP OCAM
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Morphological consequences of ΔD (1)
(Arrangement of glomeruli in the olfactory bulb)
Appropriate glomeruli are missing in ΔD mice (“empty” spaces left – competition?)
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Morphological consequences of ΔD (2)
(otherwise normal cytoarchitecture with distinct layers)
- Appropriate layers were formed (except for missing glomeruli)
TH+ = PGNsGABA+ = GCsSynaptotagmin = synapsesReelin+ = MCs
- Mitral cells in the D domain do not form dendritic terminal tufts (probably no input from OSNs).
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Functional consequences of ΔD (Zif268 + ISI)
Dorsal surface of the OB (ISI):
“unrolled” whole OB (Zif268):
ISI= intrinsic signal imaging
Zif268= immediate early gene
- No ISI odor response in the dorsal surface of the OB.
- Odorants which evoke a response in the V and D domains only activate the V domain in ΔD mice.
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Behavioral consequences of ΔD (1) (odor detection)
- The detection thresholds for pentanal and TMT were not affected, whereas it was ten-times higher for 2MB acid.
- In rats, the most responsive glomerulus for pentanal is located in the V-domain. The same seems to be true in mice, for pentanal and for TMT.
Habituation-dishabituation test:Pentanal - spoiled food (avoidance response) 2MB acid - spoiled food (avoidance response) TMT - fox urine (fear avoidance response)
Thus, ΔD mice can detect odors fairly normally
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Behavioral consequences of ΔD
(2) (odor discrimination)
Thus, ΔD can discriminate between odors normally
- In the odor discrimination test, hungry mice associate 1 odorant with sugar thus and dig longer when smelling it.
- Both wt and ΔD have similar discrimination capabilities.
-Wt mice cannot be trained to associate TMT with sugar (fear avoidance).
- ΔD do not have this problem (but they do detect it).
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Behavioral consequences of ΔD
(3) (Innate avoidance)
Aversive odors
- Innate preference test: in contrast to wt mice, ΔD mice do not display innate avoidance. They are even attracted in some cases.
- Innate avoidance test: in contrast to wt mice, ΔD mice do not display innate avoidance. They are even attracted in some cases. The same is seen in increasing concentrations of 2MB acid.
Thus, the D domain is necessary for innate avoidance
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So… ΔD mice can detect and discriminate between
odors, but they do not exhibit innate avoidance.
Can they be trained?
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Behavioral consequences of ΔD
(3) (Learned avoidance)
- Conditioned avoidance (preference
test): ΔD mice can be conditioned to avoid
aversive odors (LiCl-induced nausea).
Thus, the ΔD mice do not exhibit innate avoidance BUT they do exhibit learned avoidance
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The D domain is necessary for innate avoidance, but is
it sufficient ?
ΔII mice
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ΔII mice
(Do not have any glomeruli except the DI glomeruli)
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(DII but not DI responds to TMT so it is not
avoided)
Behavioral consequences of ΔII
(1) (Innate avoidance)
- Innate avoidance test: in
contrast to ΔD mice, ΔII mice do
display innate avoidance just like
wt mice (except in response to
TMT).
Thus, the D domain is necessary and sufficient for innate avoidance
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Two different “fear pathways”: nature and
nurture
BST
- In wt mice, the BST was strongly activated in the BST-MA, and moderately in the BST-LD.
- This is consistent with the previous observation that TMT activates the BST-MA, leading to the stimulation of the HPA axis (the “stress pathway”) in rats.
- In contrast, the BST-MA was not activated by TMT in the ΔD mice, although the BST-LD was activated as in wild-type mice.
- 2MB acid response was similar between wt and ΔD mice.
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Two different “fear pathways”: nature and
nurture
- TMT strongly activated the HPA axis (measured by ACTH) in wt mice but not in ΔD mice.
- 2MB acid also moderately activated the HPA axis.
“The Stress Pathway”:
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Two different “fear pathways”: nature and nurture
The proposed model:
- TMT activates two different neuronal pathways: one for the innate fear response (in the D-domain) and the other for the learned fear response (in the V-domain).
- For TMT, the D-domain glomeruli activate the olfactory cortex, and subsequently the BST-MA, which activates the HPA axis and causes an increase the plasma ACTH concentration.
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Eliminate a specific population of neurons
Detect morphological consequences
Detect functional consequences
Detect behavioral consequences
Show opposite behavioral consequences
Eliminate all but the specific population of neurons
“Guidelines” for discovering what a neural circuit “does”:
and to be even more persuasive, establish sufficiency (in addition to necessity):
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Question?