Metabolic sensing in AgRP neurons integrates homeostatic state with dopamine signalling in the striatum
- Monash Biomedicine Discovery Institute and Department of Physiology, Monash University, Australia
- Monash Biomedical Imaging Facility, Monash University, Australia
- Florey Institute of Neuroscience & Mental Health, Australia
- Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University, Australia
- Warwick Medical School, University of Warwick, United Kingdom
- Gene Nutrient Interactions Laboratory, Pennington Biomedical Research Center, Louisiana State University System, United States
- Departments of Psychiatry, Anesthesiology, and Neuroscience, Washington University in St Louis, United States
- School of Biomedical Sciences and Pharmacy, University of Newcastle, Australia
- Department of Biochemistry and Pharmacology, University of Melbourne, Australia
Figures
Figure 1 with 2 supplements
Deletion of Crat in AgRP neurons is a model of impaired metabolic sensing.
Intrinsic electrophysiological properties were little affected in WT versus KO mice including resting membrane potential (A, n = 22/23 cells WT/KO), input resistance (B n = 13/16 cells WT/KO), …
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Figure 1—source data 1
Deletion of Crat in AgRP neurons is a model of impaired metabolic sensing.
- https://cdn.elifesciences.org/articles/72668/elife-72668-fig1-data1-v3.zip
Figure 1—figure supplement 1
Deletion of Crat in AgRP neurons is a model of impaired metabolic sensing.
Spontaneous excitatory (A) and inhibitory (C) post-synaptic potentials compared in WT and KO mice in response to an increase in glucose from 2 mM to 5 mM. Sample traces showing examples of glucose …
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Figure 1—figure supplement 1—source data 1
Deletion of Crat in AgRP neurons is a model of impaired metabolic sensing.
- https://cdn.elifesciences.org/articles/72668/elife-72668-fig1-figsupp1-data1-v3.zip
Figure 1—figure supplement 2
Deletion of Crat from AgRP neurons does not affect ghrelin-induced food intake or AgRP activation.
Cumulative food intake measured in BioDaq feeding cages over a 24-hr (A) and 4-hr time frame (B) in WT and KO mice treated with saline (WT n = 5, KO n = 7) and ghrelin (WT n = 5, KO n = 7). No …
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Figure 1—figure supplement 2—source data 1
Deletion of Crat from AgRP neurons does not affect ghrelin-induced food intake or AgRP activation.
- https://cdn.elifesciences.org/articles/72668/elife-72668-fig1-figsupp2-data1-v3.zip
Figure 2
Impaired metabolic sensing in AgRP neurons affects dopamine release in the nucleus accumbens.
Experimental design to examine dopamine signalling in nucleus accumbens (A). Female (3 WT, 4 KO) and male (4 WT, 4 KO) mice, trained to receive peanut butter chips, were tethered to a fiber optic …
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Figure 2—source data 1
Impaired metabolic sensing in AgRP neurons affects dopamine release in the nucleus accumbens.
- https://cdn.elifesciences.org/articles/72668/elife-72668-fig2-data1-v3.zip
Figure 3
Impaired metabolic sensing in AgRP neurons affects motivation for sucrose rewards during fasting.
Mice (8 WT, 9 KO) were trained to nose poke for sucrose rewards using fixed ratio schedule (A - FR1, FR3, FR5) to reliably nose poke on average 75% correct for three consecutive nights (C), before …
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Figure 3—source data 1
Impaired metabolic sensing in AgRP neurons affects motivation for sucrose rewards during fasting.
- https://cdn.elifesciences.org/articles/72668/elife-72668-fig3-data1-v3.zip
Figure 4
Impaired metabolic sensing in AgRP neurons reduces dopamine release in the nucleus accumbens during a progressive ratio session.
Experimental design (A) - mice with fiberoptic implant in the nucleus accumbens were trained to nose poke for a sucrose pellet prior to experimental testing. During testing, mice were tethered to a …
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Figure 4—source data 1
Impaired metabolic sensing in AgRP neurons reduces dopamine release in the nucleus accumbens during a progressive ratio session.
- https://cdn.elifesciences.org/articles/72668/elife-72668-fig4-data1-v3.zip
Figure 5
The effect of impaired metabolic sensing in AgRP neurons on dopamine release in the dorsal striatum.
Experimental design to examine dopamine signalling in dorsal striatum (A): Female (2 WT, 3 KO) and male (4 WT, 4 KO) mice, trained to receive PB chips, were tethered to a fiber optic cable in their …
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Figure 5—source data 1
The effect of impaired metabolic sensing in AgRP neurons on dopamine release in the dorsal striatum.
- https://cdn.elifesciences.org/articles/72668/elife-72668-fig5-data1-v3.zip
Figure 6 with 1 supplement
Impaired metabolic sensing in AgRP neurons does not affect dopamine release in the dorsal striatum during a progressive ratio session.
Experimental design (A) - mice with a fiberoptic implant in the dorsal striatum were trained to nose poke for a sucrose pellet prior to experimental testing. During testing, mice were tethered to a …
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Figure 6—source data 1
Impaired metabolic sensing in AgRP neurons does not affect dopamine release in the dorsal striatum during a progressive ratio session.
- https://cdn.elifesciences.org/articles/72668/elife-72668-fig6-data1-v3.zip
Figure 6—figure supplement 1
Dynamic basal dopamine uptake in dorsal (A) and ventral striatum (B) in fasted mice without reward presentation and observed no differences in fDOPA uptake.
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Figure 6—figure supplement 1—source data 1
Dynamic basal dopamine uptake in dorsal and ventral striatum in fasted mice without reward presentation and observed no differences in fDOPA uptake.
- https://cdn.elifesciences.org/articles/72668/elife-72668-fig6-figsupp1-data1-v3.zip
Figure 7
Schematic representation of the approximate viral injections sites for GRAB-DA in the Nucleus Accumbens (A) and dorsal striatum (B).
AP = anterior posterior position relative to bregma.
Author response image 1
Videos
Video 1
GCaMP6s AgRP neural activity time locked to behaviour at 10 x normal speed in an ad libitum-fed WT mouse previously exposed to a peanut butter pellet.
The video shows raw data collected in mV at the photoreceiver prior to df/f calculations.
Video 2
GCaMP6s AgRP neural activity time locked to behaviour at 10 x normal speed in an ad libitum-fed KO mouse previously exposed to a peanut butter pellet.
The video shows raw data collected in mV at the photoreceiver prior to df/f calculations.
Video 3
GRAB-DA activity (dopamine release) time locked to behaviour at 10 x normal speed in an ad libitum-fed WT mouse.
The mouse is first exposed to wood dowel, followed by chow, followed by a ~ 70 mg PB chip. The video shows raw data collected in mV at the photoreceiver prior to df/f calculations.
Video 4
GRAB-DA activity (dopamine release) time locked to behaviour at 10 x normal speed in a fasted WT mouse.
The mouse is first exposed to wood dowel, followed by chow, followed by a ~ 70 mg PB chip. The video shows raw data collected in mV at the photoreceiver prior to df/f calculations.
Video 5
GRAB-DA activity (dopamine release) time locked to behaviour at 10 x normal speed in an ad libitum-fed KO mouse.
The mouse is first exposed to wood dowel, followed by chow, followed by a ~ 70 mg PB chip. The video shows raw data collected in mV at the photoreceiver prior to df/f calculations.
Video 6
GRAB-DA activity (dopamine release) time locked to behaviour at 10 x normal speed in a fasted KO mouse.
The mouse is first exposed to wood dowel, followed by chow, followed by a ~ 70 mg PB chip. The video shows raw data collected in mV at the photoreceiver prior to df/f calculations.
