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Rodents are not able to report migraine symptoms. Here, we describe a manageable test paradigm (light/dark and open field assays) to measure light aversion, one of the most common and bothersome symptoms in patients with migraines.
Migraine is a complex neurological disorder characterized by headache and sensory abnormalities, such as hypersensitivity to light, observed as photophobia. Whilst it is impossible to confirm that a mouse is experiencing migraine, light aversion can be used as a behavioral surrogate for the migraine symptom of photophobia. To test for light aversion, we utilize the light/dark assay to measure the time mice freely choose to spend in either a light or dark environment. The assay has been refined by introducing two critical modifications: pre-exposures to the chamber prior to running the test procedure and adjustable chamber lighting, permitting the use of a range of light intensities from 55 lux to 27,000 lux. Because the choice to spend more time in the dark is also indicative of anxiety, we also utilize a light-independent anxiety test, the open field assay, to distinguish anxiety from light-aversive behavior. Here, we describe a modified test paradigm for the light/dark and open field assays. The application of these assays is described for intraperitoneal injection of calcitonin gene-related peptide (CGRP) in two mouse strains and for optogenetic brain stimulation studies.
Migraine is a prevalent neurological disease, affecting approximately 17% of Americans1 and is the second leading cause of disability globally2,3. Patients experience headache that lasts 4-72 hours accompanied with at least one of the following symptoms: nausea and/or vomiting, or photophobia and phonophobia4. Recent advances in the development of calcitonin gene-related peptide (CGRP) antibodies that are now FDA approved have begun a new era for migraine treatment5,6,7.....
Animal procedures were approved by the University of Iowa Animal Care and Use Committee and performed in compliance with the standards set by the National Institutes of Health.
1. Light/dark assay
This behavioral test paradigm is designed to test light-aversive behavior. It can be performed using both naïve wildtype mice and optogenetic mice to investigate light aversion in real time during the stimulation of a targeted neuronal population.
This procedure has been used to study the effect of peripheral CGRP treatment in CD1 and C57BL/6J mice10,16 and optical stimulation of neurons in the posterior thalamic nuclei in C57BL/6.......
The light/dark assay is widely used to assess anxiety-like behavior12. The assay relies on the innate aversion of mice to light and their drive to explore when placed into a novel environment (light zone). However, as we report here, this assay can also be used to assess light-aversive behavior as well.
It is critical to consider the number and necessity of pre-exposures prior to testing. This depends on the mouse strain or model. For example, in our light/dark assay pr.......
This work was supported by grants from the NIH NS R01 NS075599 and RF1 NS113839. The contents do not represent the views of VA or the United States Government.
....Name | Company | Catalog Number | Comments |
Activity monitor | Med Assoc. Inc | Software tracking mouse behavior | |
Customized acrylic shelf | For adjusting the height of the LED panel | ||
Dark box insert | Med Assoc. Inc | ENV-511 | |
DC power supply | Med Assoc. Inc | SG-500T | |
DC regulated power supply | Med Assoc. Inc | SG-506 | |
Fiber-optic cannula | Doric | MFC_200/ 240-0.22_4.5mm_ZF1.25_FLT | |
Germicidal disposable wipes | Sani-Cloth | SKU # Q55172 | |
Heat Sink | Wakefield | 490-6K | Connecting to LED panel |
IR controller power cable | Med Assoc. Inc | SG-520USB-1 | |
IR USB controller | Med Assoc. Inc | ENV-520USB | |
Mating sleeve | Doric | SLEEVE_ZR_1.25 | |
Modified LED light panel | Genaray Spectro | SP-E-360D | Daylight-balanced color (5600K) |
Power supply | MEAN WELL USA | SP-320-12 | Connecting to LED panel |
Seamless open field chamber | Med Assoc. Inc | ENV-510S | |
Sound-attenuating cubicle | Med Assoc. Inc | ENV-022MD-027 | |
Stand and clamp | |||
Three 16-beam IR arrays | Med Assoc. Inc | ENV-256 |
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