Circuit mechanisms encoding odors and driving aging-associated behavioral declines in Caenorhabditis elegans
- University of California, San Diego, United States
- Salk Institute for Biological Studies, United States
- University of Michigan, United States
- Worcester Polytechnic Institute, United States
Figures
Figure 1 with 1 supplement
Multiple sensory neurons detect the odor benzaldehyde (BZ).
(A) Image of a young adult C. elegans and schematic depicting the twelve pairs of sensory neurons in the anterior amphid ganglia whose dendrites project to the nose of the animal where they detect …
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Figure 1—source data 1
Young adult chemotaxis performance data.
- https://doi.org/10.7554/eLife.10181.004
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Figure 1—source data 2
Odor-evoked responses in wild-type young adult data.
- https://doi.org/10.7554/eLife.10181.005
Figure 1—figure supplement 1
Combinatorial olfactory coding in C. elegans.
(A) Maximum ΔF/F of each individual wild-type animal's AWCON, AWA, ASEL or AWB neuron response to medium BZ. (B) Quantification of the time to maximum ΔF/F following stimulus change for each …
Figure 2
Cell ablation reveals primary and secondary BZ sensory neurons.
(A) Average young adult AWCON neuron responses to medium BZ in control (Ctrl) mock-ablated animals compared to animals with the AWA, ASE or AWB sensory neurons ablated (neurons ablated at an early …
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Figure 2—source data 1
Odor responses in cell ablated animal data.
- https://doi.org/10.7554/eLife.10181.008
Figure 3 with 1 supplement
Primary olfactory neurons release neuropeptides and classical neurotransmitters to recruit secondary neurons into the BZ circuit.
(A, B) Average young adult (A) AWCON and (B) AWA neuron calcium responses to BZ in wild-type, unc-13 mutants with impaired synaptic vesicle release, and unc-31 mutants with impaired dense core …
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Figure 3—source data 1
Odor responses in neurotransmitter release pathway genetic mutant data.
- https://doi.org/10.7554/eLife.10181.010
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Figure 3—source data 2
Odor responses in genetic mutant data.
- https://doi.org/10.7554/eLife.10181.011
Figure 3—figure supplement 1
Primary and secondary olfactory neurons respond to BZ.
(A-D) Average calcium responses of young adult (A) AWCOFF, (B) ASER, (C) ASEL and (D) AWB neurons in wild-type, unc-13 mutants with impaired synaptic vesicle release, and unc-31 mutants with …
Figure 4 with 1 supplement
Insulin peptidergic and cholinergic transmission from the two primary olfactory sensory neurons recruits two secondary olfactory neurons.
(A) BZ-evoked activity in young adult ASEL neurons in wild-type, ins-1 insulin-like peptide mutants, ins-1; AWC-specific ins-1 rescue and ins-1; AWA-specific ins-1 rescue. (B) Average ASEL responses …
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Figure 4—source data 1
Odor responses and chemotaxis performance in insulin and acetycholine pathway mutant and transgenic data.
- https://doi.org/10.7554/eLife.10181.014
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Figure 4—source data 2
Additional odor responses in insulin and acetycholine pathway mutant and transgenic data.
- https://doi.org/10.7554/eLife.10181.015
Figure 4—figure supplement 1
Odor-evoked calcium dynamics in genetic mutants.
(A–C) Young adult AWCON neuron average responses to BZ stimulation in wild-type animals compared to (A) insulin-like peptide ins-1 mutants, (B) daf-2 insulin receptor mutants and (C) age-1 …
Figure 5 with 5 supplements
BZ-evoked secondary neuron activity and behavior specifically degrade with age.
(A) Chemotaxis performance of wild-type worms from young adulthood (day 1) through early stage aging (day 6) towards a point source of medium BZ. (B) Speed of wild-type young (day 1) and aged (day …
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Figure 5—source data 1
Age-related decay in odor responses and chemotaxis behavior data.
- https://doi.org/10.7554/eLife.10181.018
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Figure 5—source data 2
Primary and secondary neuron activity in young and aged animal data.
- https://doi.org/10.7554/eLife.10181.019
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Figure 5—source data 3
Correlated behavior and functional imaging in aged animal data.
- https://doi.org/10.7554/eLife.10181.020
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Figure 5—source data 4
Dose-dependent odor response data.
- https://doi.org/10.7554/eLife.10181.021
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Figure 5—source data 5
Salt and 2-nonanone responses in young and aged animal data.
- https://doi.org/10.7554/eLife.10181.022
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Figure 5—source data 6
Longevity mutant odor response data.
- https://doi.org/10.7554/eLife.10181.023
Figure 5—figure supplement 1
Quantification of BZ-evoked primary and secondary neuron activity in young and aged animals.
(A) Measurement of the perimeter of day 5 aged worms and the more variable day 6 aged worms (see ‘Materials and methods’ section). Thick red line shows mean and error bars represent standard …
Figure 5—figure supplement 2
Olfactory behavior in aged animals is correlated with reliability of odor-evoked neuronal activity.
(A) Schematic of animals from a chemotaxis assay washed and sorted into two populations, based on success or failure in navigating up the BZ odor gradient, for calcium imaging. (B, C) Heat maps of …
Figure 5—figure supplement 3
Dose-dependent odor-evoked calcium dynamics in young and aged adults.
(A) Chemotaxis performance of wild-type worms of different ages towards a point source of high concentration BZ. Numbers on bars represent number of assay plates and error bars indicate s.e.m. NS, p …
Figure 5—figure supplement 4
ASE and AWB primary responses to salt and 2-nonanone, respectively, remain reliable with aging.
(A) Chemotaxis performance of wild-type young (day 1) and aged (day 5) adults towards a point source of 500 mM NaCl. NS p > 0.05, two-tailed t-test. (B) Heat maps of ratio change in fluorescence to …
Figure 5—figure supplement 5
Long and short-lived mutants do not influence the aging-associated declines in neuronal function.
(A, B) Heat maps of ratio change in fluorescence to total fluorescence for aged adult (day 5) (A) ASEL and (B) AWB neurons stimulated with medium BZ (0.005% vol/vol) in wild-type, glp-1 mutants and a…
Figure 6 with 1 supplement
Increased neurotransmitter release from AWC neurons rescues aging-associated ASEL activity and behavioral deficits.
(A) Schematic representation of genetic manipulations to overcome aging-associated decay of neurotransmission. (B–E) Heat maps of ratio change in fluorescence to total fluorescence for aged adult …
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Figure 6—source data 1
Odor responses in AWC-released neurotransmitter manipulation animal data.
- https://doi.org/10.7554/eLife.10181.030
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Figure 6—source data 2
Additional odor responses in AWC-released neurotransmitter manipulation animal data.
- https://doi.org/10.7554/eLife.10181.031
Figure 6—figure supplement 1
AWC-released neurotransmitters modify aging-associated neuronal activity and behavioral deficits.
(A) Heat maps of ratio change in fluorescence to total fluorescence for young adult (day 1) ASEL neuron responses to medium BZ (0.005% vol/vol) in wild-type animals and in transgenic animals with …
Figure 7 with 1 supplement
Increased release from AWA primary neurons rescues aging-associated AWB activity and behavioral deficits.
(A) Schematic representation of genetic and pharmacologic manipulations to overcome aging-associated decay of neurotransmission. (B–D) Heat maps of ratio change in fluorescence to total fluorescence …
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Figure 7—source data 1
Odor responses in AWA-released neurotransmitter manipulation animal data.
- https://doi.org/10.7554/eLife.10181.034
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Figure 7—source data 2
Additional odor responses in AWA-released neurotransmitter manipulation animal data.
- https://doi.org/10.7554/eLife.10181.035
Figure 7—figure supplement 1
AWA neurotransmission modifies aging-associated neuronal activity and behavioral deficits.
(A) Heat maps of ratio change in fluorescence to total fluorescence for young (day 1) adult AWB neuron responses to medium BZ (0.005% vol/vol) in wild-type animals, transgenic animals with …
Figure 8 with 3 supplements
Aged animal olfactory abilities and neurotransmission from primary neurons are correlated with lifespan.
(A) Schematic of animals from a chemotaxis assay washed and sorted into two populations based on successful or failed navigation up the BZ odor gradient, for lifespan analysis. (B) Animals that …
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Figure 8—source data 1
Lifespan of animals sorted by their chemotaxis performance and lifespan of neurotransmitter manipulation transgenic animal data.
- https://doi.org/10.7554/eLife.10181.038
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Figure 8—source data 2
Additional lifespan of neurotransmitter manipulation transgenic animal data.
- https://doi.org/10.7554/eLife.10181.039
Figure 8—figure supplement 1
Sorting animals based on their performance on odor chemotaxis affects lifespan.
Wild-type (N2) worms were separated into a population that successfully reached the BZ odor or salt side of the chemotaxis plate and a population that failed to do so (Ctrl side) as young adults …
Figure 8—figure supplement 2
Sorting animals based on their performance on salt chemotaxis and silencing primary neurons modifies lifespan.
(A) Animals sorted by their aged (day 5) adult chemotaxis to sodium chloride do not have significantly different lifespans (see Figure 8—figure supplement 1 and Figure 8—source data 2 for …
Figure 8—figure supplement 3
Manipulating neurotransmission from primary olfactory neurons modifies lifespan.
The survival of wild-type, AWC-neuron specific tom-1 RNAi, AWC-specific ins-1 OE, AWA-specific unc-17 OE, AWA-specific tetanus toxin expression and AWC-specific tetanus toxin expression transgenic …
Tables
Author response table 1
Comparison of Averaged ΔF/F in 10s time window listed below for young and aged WT odor responsive neurons (by two-tailed t-test)
Neuron | 10-20s | 20-30s | 30-40s | 40-50s | 50-60s | 60-70s |
|---|---|---|---|---|---|---|
AWCON | NS, P=0.1682 | NS, P=0.2114 | NS, P=0.2306 | NS, P=0.3829 | NS, P=0.4481 | NS, P=0.5167 |
ASEL | NS, P=0.2593 | NS, P=0.1983 | NS, P=0.1421 | NS, P=0.2748 | NS, P=0.2067 | NS, P=0.1822 |
AWB | NS, P=0.0601 | NS, P=0.1168 | NS, P=0.1327 | NS, P=0.2933 | NS, P=0.3453 | NS, P=0.3298 |
Neuron | 70-80s | 80-90s | 90-100s | 100-110s | 110-120s | 120-129s |
AWCON | NS, P=0.4226 | NS, P=0.4927 | NS, P=0.4857 | NS, P=0.5729 | NS, P=0.5361 | NS, P=0.6571 |
ASEL | NS, P=0.1531 | NS, P=0.1408 | NS, P=0.1446 | NS, P=0.1471 | NS, P=0.0620 | NS, P=0.0895 |
AWB | NS, P=0.2249 | NS, P=0.4059 | NS, P=0.2927 | NS, P=0.3530 | NS, P=0.2368 | NS, P=0.2538 |
Author response table 2
Is there a significant difference between the young and the aged odor responsive neurons?
Neuron | 130-140s | 140-150s | 150-160s | 160-170s | 170-180s |
|---|---|---|---|---|---|
AWCON | NS, P=0.0643 | NS, P=0.1383 | NS, P=0.6332 | NS, P=0.1942 | NS, P=0.0939 |
ASEL | *P=0.0336 | NS, P=0.0599 | NS, P=0.1584 | NS, P=0.4384 | NS, P=0.4712 |
AWB | NS, P=0.0909 | NS, P=0.0709 | NS, P=0.0886 | NS, P=0.3076 | NS, P=0.5934 |
Neuron | 10-20s | 20-30s | 30-40s | 40-50s | 50-60s |
AWA | NS, P=0.3929 | NS, P=0.3771 | NS, P=0.1101 | NS, P=0.1425 | NS, P=0.1957 |
Additional files
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Supplementary file 1
C. elegans strain list.
- https://doi.org/10.7554/eLife.10181.043
