Investigating Migraine-Like Behavior Using Light Aversion in Mice

Summary

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.

Abstract

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.

Introduction

Migraine is a prevalent neurological disease, affecting approximately 17% of Americans¹ and is the second leading cause of disability globally^2,3. 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 treatment^5,6,7.....

Protocol

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

1. Light/dark chamber apparatus (see Table of Materials) setup. All the equipment in this section is commercially available.
   1. On a shelf, place the sound-attenuating cubicle (interior: 59.7 x 38 x 35.6 cm in W x H x D) containing a pull-out drawer for easy access .......

Discussion

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.......

Materials

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