Neurobiological links between stress and anxiety

Daviu, Núria; Bruchas, Michael R.; Moghaddam, Bita; Sandi, Carmen; Beyeler, Anna

doi:10.1016/j.ynstr.2019.100191

“…Nuclei of the amygdala help to regulate emotional stress and pain perception (82)(83)(84). Elevated baseline activity in the amygdala is associated with fibromyalgia-induced and inflammatory bowel syndrome-induced chronic pain and depression.…”

Section: Amygdalamentioning

confidence: 99%

The Mesolimbic Dopamine System in Chronic Pain and Associated Affective Comorbidities

Serafini

¹

,

Pryce

²

,

Zachariou

³

2020

Biological Psychiatry

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Chronic pain is a complex neuropsychiatric disorder characterized by sensory, cognitive, and affective symptoms. Over the past 2 decades, researchers have made significant progress toward understanding the impact of mesolimbic dopamine circuitry in acute and chronic pain. These efforts have provided insights into the circuits and intracellular pathways in the brain reward center that are implicated in sensory and affective manifestations of chronic pain. Studies have also identified novel therapeutic targets as well as factors that affect treatment responsiveness. Dysregulation of dopamine function in the brain reward center may further promote comorbid mood disorders and vulnerability to addiction. This review discusses recent clinical and preclinical findings on the neuroanatomical and neurochemical adaptations triggered by prolonged pain states in the brain reward pathway. Furthermore, this discussion highlights evidence of mechanisms underlying comorbidities among pain, depression, and addiction.

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“…Insular neurons were shown to project to the amygdala [60], a region essential for emotional processing, including valence and anxiety [45,[63][64][65]. The insula is also known to project to the lateral hypothalamus (LH), controlling autonomous responses which are part of anxiety symptoms [54].…”

Section: Circuit Specific Expression Of 5-ht Receptorsmentioning

confidence: 99%

Expression of serotonin 1A and 2A receptors in molecular- and projection-defined neurons of the mouse insular cortex

Ju

¹

,

Fernandez-Arroyo

²

,

Wu

³

et al. 2020

Preprint

Self Cite

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Abstract The serotonin (5-HT) system is the target of multiple anxiolytics, including Buspirone, which is a partial agonist of the serotonin 1A receptor (5‑HT1A). Similarly, ligands of the serotonin 2A receptor (5-HT2A) were shown to alter anxiety level. The 5-HT1A and 2A receptors are widely expressed across the brain, but the target region(s) underlying the influence of those receptors on anxiety remain unknown. Interestingly, recent studies in human and non-human primates have shown that the 5-HT1A and 5-HT2A binding potential within the insular cortex (insula) are correlated to anxiety. As an initial step to define the function of 5‑HT transmission in the insula, we quantified the proportion of specific neuronal populations of the insula expressing 5‑HT1A or 5‑HT2A. We analyzed seven neural populations, including three defined by a molecular marker (putative glutamate, GABA or parvalbumin), and four defined by their projections to different downstream targets. First, we found that more than 70% of putative glutamatergic neurons, and only 30% of GABAergic neurons express the 5‑HT1A. Second, within insular projection neurons, 5-HT1A is highly expressed (75-80%) in the populations targeting one sub-nuclei of the amygdala (central or basolateral), or targeting the rostral or caudal sections of the lateral hypothalamus (LH). Similarly, 70% of putative glutamatergic neurons and only 30% of insular GABAergic neurons contain 5-HT2A. Finally, the 5-HT2A is present in a majority of insula-amygdala and insula-LH projection neurons (73-82%). These observations suggest that most glutamatergic neurons can respond to 5‑HT through 5-HT1A or 5‑HT2A in the insula, and that 5-HT directly affects a limited number of GABAergic neurons. This study defines a molecular and neuroanatomical map of the 5-HT system within the insular cortex, providing ground knowledge to identify the potential role of serotonergic modulation of selective insular populations in anxiety.

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“…Insular neurons were shown to project to the amygdala [50], a region essential for emotional processing, including valence and anxiety [45,[53][54][55]. The insula is also known to project to the lateral hypothalamus (LH), controlling autonomous responses which are part of anxiety symptoms [43].…”

Section: Circuit Specific Expression Of 5-ht Receptorsmentioning

confidence: 99%

Expression of serotonin 1A and 2A receptors in molecular- and projection-defined neurons of the mouse insular cortex

Ju

¹

,

Fernandez-Arroyo

²

,

Wu

³

et al. 2020

Preprint

Self Cite

0

View full text Add to dashboard Cite

Abstract The serotonin (5-HT) system is the target of multiple anxiolytics, including Buspirone, which is a partial agonist of the serotonin 1A receptor (5‑HT1A). Similarly, ligands of the serotonin 2A receptor (5-HT2A) were shown to alter anxiety level. The 5-HT1A and 2A receptors are widely expressed across the brain, but the target region(s) underlying the influence of those receptors on anxiety remain unknown. Interestingly, recent studies in human and non-human primates have shown that the 5-HT1A and 5-HT2A binding potential within the insular cortex (insula) are correlated to anxiety. As an initial step to define the function of 5‑HT transmission in the insula, we quantified the proportion of specific neuronal populations of the insula expressing 5‑HT1A or 5‑HT2A. We analyzed seven neural populations, including three defined by a molecular marker (putative glutamate, GABA or parvalbumin), and four defined by their projections to different downstream targets. First, we found that more than 70% of putative glutamatergic neurons, and only 30% of GABAergic neurons express the 5‑HT1A. Second, within insular projection neurons, 5-HT1A is highly expressed (75-80%) in the populations targeting one sub-nuclei of the amygdala (central or basolateral), or targeting the rostral or caudal sections of the lateral hypothalamus (LH). Similarly, 70% of putative glutamatergic neurons and only 30% of insular GABAergic neurons contain 5-HT2A. Finally, the 5-HT2A is present in a majority of insula-amygdala and insula-LH projection neurons (73-82%). These observations suggest that most glutamatergic neurons can respond to 5‑HT through 5-HT1A or 5‑HT2A in the insula, and that 5-HT directly affects a limited number of GABAergic neurons. This study defines a molecular and neuroanatomical map of the 5-HT system within the insular cortex, providing ground knowledge to identify the potential role of serotonergic modulation of selective insular populations in anxiety.

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Neurobiological links between stress and anxiety

Cited by 288 publications

References 93 publications

The Mesolimbic Dopamine System in Chronic Pain and Associated Affective Comorbidities

The Mesolimbic Dopamine System in Chronic Pain and Associated Affective Comorbidities

Expression of serotonin 1A and 2A receptors in molecular- and projection-defined neurons of the mouse insular cortex

Expression of serotonin 1A and 2A receptors in molecular- and projection-defined neurons of the mouse insular cortex

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