Stimulation of Posterior Thalamic Nuclei Induces Photophobic Behavior in Mice.

Published on Oct 1, 2020in Headache4.041
· DOI :10.1111/HEAD.13917
Levi P. Sowers10
Estimated H-index: 10
(UI: University of Iowa),
Mengya Wang2
Estimated H-index: 2
(UI: University of Iowa)
+ 7 AuthorsAndrew F. Russo46
Estimated H-index: 46
OBJECTIVE A hallmark of migraine is photophobia. In mice, photophobia-like behavior is induced by calcitonin gene-related peptide (CGRP), a neuropeptide known to be a key player in migraine. In this study, we sought to identify sites within the brain from which CGRP could induce photophobia. DESIGN We focused on the posterior thalamic region, which contains neurons responsive to both light and dural stimulation and has CGRP binding sites. We probed this area with both optogenetic stimulation and acute CGRP injections in wild-type mice. Since the light/dark assay has historically been used to investigate anxiety-like responses in animals, we measured anxiety in a light-independent open field assay and asked if stimulation of a brain region, the periaqueductal gray, that induces anxiety would yield similar results to posterior thalamic stimulation. The hippocampus was used as an anatomical control to ensure that light-aversive behaviors could not be induced by the stimulation of any brain region. RESULTS Optogenetic activation of neuronal cell bodies in the posterior thalamic nuclei elicited light aversion in both bright and dim light without an anxiety-like response in an open field assay. Injection of CGRP into the posterior thalamic region triggered similar light-aversive behavior without anxiety. In contrast to the posterior thalamic nuclei, optogenetic stimulation of dorsal periaqueductal gray cell bodies caused both light aversion and an anxiety-like response, while CGRP injection had no effect. In the dorsal hippocampus, neither optical stimulation nor CGRP injection affected light aversion or open field behaviors. CONCLUSION Stimulation of posterior thalamic nuclei is able to initiate light-aversive signals in mice that may be modulated by CGRP to cause photophobia in migraine.
📖 Papers frequently viewed together
86 Citations
15 Citations
11 Citations
#1Yinglu Liu (Xi'an Jiaotong University)H-Index: 1
#1Yinglu Liu (Xi'an Jiaotong University)H-Index: 1
Last. Min Zhuo (Xi'an Jiaotong University)H-Index: 89
view all 6 authors...
Recent studies demonstrate that calcitonin gene-related peptide (CGRP) plays critical roles in migraine. Immunohistochemistry and in situ hybridization studies have shown that CGRP and its receptors are expressed in cortical areas that are critical for pain perception including the anterior cingulate cortex (ACC) and insular cortex (IC). Recent studies reported that CGRP enhanced excitatory transmission in the ACC. However, little is known about the possible effect of CGRP on excitatory transmis...
4 CitationsSource
#1Anne-Sophie Wattiez (UI: University of Iowa)H-Index: 6
#2Levi P. Sowers (UI: University of Iowa)H-Index: 10
Last. Andrew F. Russo (UI: University of Iowa)H-Index: 46
view all 3 authors...
ABSTRACTIntroduction: The neuropeptide calcitonin gene-related peptide (CGRP) is recognized as a critical player in migraine pathophysiology. Excitement has grown regarding CGRP because of the deve...
12 CitationsSource
#1Rodrigo Noseda (BIDMC: Beth Israel Deaconess Medical Center)H-Index: 21
#2David R. Copenhagen (UCSF: University of California, San Francisco)H-Index: 51
Last. Rami Burstein (BIDMC: Beth Israel Deaconess Medical Center)H-Index: 76
view all 3 authors...
ObjectiveTo review clinical and pre-clinical evidence supporting the role of visual pathways, from the eye to the cortex, in the development of photophobia in headache disorders.BackgroundPhotophobia is a poorly understood light-induced phenomenon that emerges in a variety of neurological and ophthalmological conditions. Over the years, multiple mechanisms have been proposed to explain its causes; however, scarce research and lack of systematic assessment of photophobia in patients has made the ...
28 CitationsSource
#1Carolyn A. Bernstein (Harvard University)H-Index: 8
#2Rony-Reuven Nir (Harvard University)H-Index: 3
Last. Rami BursteinH-Index: 76
view all 11 authors...
: Migraine-type photophobia, most commonly described as exacerbation of headache by light, affects nearly 90% of the patients. It is the most bothersome symptom accompanying an attack. Using subjective psychophysical assessments, we showed that migraine patients are more sensitive to all colors of light during ictal than during interictal phase and that control subjects do not experience pain when exposed to different colors of light. Based on these findings, we suggested that color preference i...
12 CitationsSource
#1Xu-Hui Li (Xi'an Jiaotong University)H-Index: 13
#2Takanori Matsuura (U of T: University of Toronto)H-Index: 3
Last. Min Zhuo (Xi'an Jiaotong University)H-Index: 89
view all 5 authors...
The neuropeptide of calcitonin gene-related peptide (CGRP) plays critical roles in chronic pain, especially in migraine. Immunohistochemistry and in situ hybridization studies have shown that CGRP ...
13 CitationsSource
#1Andrew F. Russo (UI: University of Iowa)H-Index: 46
Migraine is a debilitating neurological condition that involves the neuropeptide calcitonin gene-related peptide (CGRP). An exciting development is the recent FDA approval of the first in an emerging class of CGRP-targeted drugs designed to prevent migraine. Yet despite this efficacy, there are some fundamental unanswered questions, such as where and how CGRP works in migraine. Preclinical data suggest that CGRP acts via both peripheral and central mechanisms. The relevance of peripheral sites i...
12 CitationsSource
#1Jane Y Chen (UW: University of Washington)H-Index: 2
#2Carlos A. Campos (UW: University of Washington)H-Index: 5
Last. Richard D. Palmiter (UW: University of Washington)H-Index: 161
view all 4 authors...
Summary Food aversions develop when the taste of a novel food is associated with sickness, which often occurs after food poisoning or chemotherapy treatment. We identified calcitonin-gene-related peptide (CGRP) neurons in the parabrachial nucleus (PBN) as sufficient and necessary for establishing a conditioned taste aversion (CTA). Photoactivating projections from CGRP PBN neurons to either the central nucleus of the amygdala or the bed nucleus of the stria terminalis can also induce robust CTA....
44 CitationsSource
#1Lars Jacob StovnerH-Index: 73
#2Emma NicholsH-Index: 28
Last. Christopher J L MurrayH-Index: 220
view all 53 authors...
Summary Background Through the Global Burden of Diseases, Injuries, and Risk Factors (GBD) studies, headache has emerged as a major global public health concern. We aimed to use data from the GBD 2016 study to provide new estimates for prevalence and years of life lived with disability (YLDs) for migraine and tension-type headache and to present the methods and results in an accessible way for clinicians and researchers of headache disorders. Methods Data were derived from population-based cross...
405 CitationsSource
#1John SimmsH-Index: 23
#2Romez Uddin (Aston University)H-Index: 4
Last. David R. Poyner (Aston University)H-Index: 43
view all 10 authors...
Calcitonin gene-related peptide (CGRP) binds to the complex of the calcitonin receptor-like receptor (CLR) with receptor activity-modifying protein 1 (RAMP1). How CGRP interacts with the transmembrane domain (including the extracellular loops) of this family B receptor remains unclear. In this study, a photoaffinity cross-linker, p-azido l-phenylalanine (azF), was incorporated into CLR, chiefly in the second extracellular loop (ECL2) using genetic code expansion and unnatural amino acid mutagene...
10 CitationsSource
#1Dominic A. Evans (LMB: Laboratory of Molecular Biology)H-Index: 3
#2A. Vanessa Stempel (LMB: Laboratory of Molecular Biology)H-Index: 8
Last. Tiago Branco (LMB: Laboratory of Molecular Biology)H-Index: 25
view all 6 authors...
Escaping from imminent danger is an instinctive behaviour that is fundamental for survival, and requires the classification of sensory stimuli as harmless or threatening. The absence of threat enables animals to forage for essential resources, but as the level of threat and potential for harm increases, they have to decide whether or not to seek safety 1 . Despite previous work on instinctive defensive behaviours in rodents2–11, little is known about how the brain computes the threat level for i...
157 CitationsSource
Cited By2
#1Brandon Baksh (UM: University of Miami)H-Index: 1
#2Julia Costa Garcia (UM: University of Miami)
Last. Anat Galor (UM: University of Miami)H-Index: 24
view all 3 authors...
Dry eye and migraine are common diseases with large societal and economic burdens that have recently been associated in the literature. This review outlines the link between dry eye and migraine, which may have implications for reducing their respective burdens. We highlight possible shared pathophysiology, including peripheral and central sensitization, as the potential link between dry eye and migraine. Finally, therapies targeting similar pathophysiological mechanisms between dry eye and migr...
#1Mengya WangH-Index: 2
Last. Andrew F. RussoH-Index: 46
view all 3 authors...