How an anxious heart talks to the brain

Couderc, Yoni; Beyeler, Anna

doi:10.1038/d41586-023-00502-6

Cited by 3 publications

(2 citation statements)

References 10 publications

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“…This may be explained by the fact that neuroinflammation contributes to anxious and depressive behavior (Guo et al 2023). In particular, neuroinflammation in ACC is associated with mood disorders (Matisz and Gruber 2022;Zhou et al 2022), also activity in posterior insular cortex correlates with heart-induced anxiety (Couderc and Beyeler 2023;Hsueh et al 2023). Furthermore, our results are very relevant for ADHD management in patients since anxiety occurs as a comorbid symptom in approximately 50% of cases studied (Bishop et al 2019), providing an alternative therapeutic tool.…”

Section: Discussionmentioning

confidence: 62%

Abscisic Acid rescues behavior in adult female mice in Attention Deficit Disorder with Hyperactivity model of dopamine depletion by regulating microglia and increasing Vesicular GABA Transporter expression

Meseguer-Beltrán,

Sánchez-Sarasúa,

Kerekes

et al. 2024

Preprint

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Background: Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental syndrome influenced by both genetic and environmental factors. While genetic studies have highlighted catecholamine dysfunction, emerging epidemiological evidence suggest neuroinflammation as a significant trigger. However, understanding the relative contributions of these alterations to ADHD symptomatology remains elusive. Method: This study employed 93 female Swiss mice of the ADHD dopamine deficit model. Dopaminergic lesions were induced via 6-hydroxidopamine (6-OHDA) injection on postnatal day 5. The impact of these lesions during development was examined by comparing young and adult mice (at postnatal day 21 and 90, respectively). We sought to mitigate adult symptoms through abscisic acid (ABA) administration during two-months. Postmortem analyses encompassed the evaluation of neuroinflammation (microglia morphology, NLRP3 inflammasome activation, cytokine expression) and excitatory/inhibitory (E/I) ratio in specific brain regions. Results: Neonatal dopaminergic lesions elicited hyperactivity, impulsivity, increased social interaction in both young and adult females and lesion induce impaired memory in adults. ABA exposure significantly ameliorated hyperactivity, impulsivity, anxiety, hypersensitivity, and social interaction alterations, but not cognitive impairment in adults. In the anterior cingulate cortex (ACC) of young mice dopamine-deficit induced microglia morphology alterations, elevated IL-1β and TNFa expression and reduced Arg1 mRNA levels, along with E/I imbalance. ABA intervention restored microglia morphology, IL-1β expression and enhanced vGAT levels. Conclusions: This study strongly suggest that dopamine deficit induced alteration of microglia and E/I ratio underling distinct ADHD symptoms. Reinstating healthy microglia by anti-inflammatory agents in specific areas emerges as a promising strategy for managing ADHD.

show abstract

Section: Discussionmentioning

confidence: 62%

Abscisic Acid rescues behavior in adult female mice in Attention Deficit Disorder with Hyperactivity model of dopamine depletion by regulating microglia and increasing Vesicular GABA Transporter expression

Meseguer-Beltrán,

Sánchez-Sarasúa,

Kerekes

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…This may be explained by the fact that neuroinflammation contributes to anxious and depressive behavior (77). In particular, neuroinflammation in ACC is associated with mood disorders (78,79), also activity in posterior insular cortex correlates with heart-induced anxiety (80,81). Furthermore, our results are very relevant for ADHD management in patients since anxiety occurs as a comorbid symptom in approximately 50% of cases studied (82), providing an alternative therapeutic tool.…”

Section: Discussionmentioning

confidence: 99%

Abscisic Acid rescues behavior in adult female mice in Attention Deficit Disorder with Hyperactivity model of dopamine depletion by regulating microglia and vesicular GABA transporter

Meseguer-Beltrán,

Sánchez-Sarasúa,

Kerekes

et al. 2024

Preprint

View full text Add to dashboard Cite

Background: Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental syndrome influenced by both genetic and environmental factors. While genetic studies have highlighted catecholamine dysfunction, emerging epidemiological evidence suggest neuroinflammation as a significant trigger. However, understanding the relative contributions of these alterations to ADHD symptomatology remains elusive. Method: This study employed 93 female Swiss mice of the ADHD dopamine deficit model. Dopaminergic lesions were induced via 6-hydroxidopamine (6-OHDA) injection on postnatal day 5. The impact of these lesions during development was examined by comparing young and adult mice (at postnatal day 21 and 90, respectively). We sought to mitigate adult symptoms through abscisic acid (ABA) administration during two-months. Postmortem analyses encompassed the evaluation of neuroinflammation (microglia morphology, NLRP3 inflammasome activation, cytokine expression) and excitatory/inhibitory (E/I) ratio in specific brain regions. Results: Neonatal dopaminergic lesions elicited hyperactivity, impulsivity, hypersensitivity increased social interaction in both one-month and three-month females and induced impaired memory in three-month mice. ABA exposure significantly ameliorated hyperactivity, impulsivity, anxiety, hypersensitivity, and social interaction alterations, but not cognitive impairment. In the anterior cingulate cortex (ACC) of one-month mice dopamine-deficit elevated IL-1β and TNF-alpha; expression and reduced Arg1 mRNA levels, along with E/I imbalance. ABA intervention restored microglia morphology, IL-1beta, Arg1 expression and enhanced vGAT levels. Conclusions: This study strongly suggest that dopamine deficit induced alteration of microglia and E/I ratio underling distinct ADHD symptoms. Reinstating healthy microglia by anti-inflammatory agents in specific areas emerges as a promising strategy for managing ADHD

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Dopamine transmission in the anterior insula shapes the neural coding of anxiety

Couderc,

Reddy,

Vardiero

et al. 2024

Preprint

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The insular cortex (or insula), and particularly its anterior region, plays a crucial role in the control of emotional valence and anxiety (Etkin & Wager, 2007; Mendez-Ruette et al., 2019; Nicolas et al., 2023). While dopamine neurotransmission is known to modulate anxiety levels in humans (Hjorth et al., 2021) and animal models (de la Mora et al., 2010; Bananej et al., 2012; Zarrindast & Khakpai, 2015; DeGroot et al., 2020; Godino et al., 2023), its regulatory effects on the anterior insula remained unexplored. Here, using a multifaceted approach, we uncovered how dopamine shapes anterior insula function in anxiety and valence processing. First, we revealed a high density of neurons expressing type-1 dopamine receptors (D1) in the insula, particularly important in the anterior insula, and seven times greater than the density of neurons expressing type-2 dopamine receptors (D2). Few neurons co-expressed Drd1 and Drd2 mRNAs in the anterior and posterior insula, and the density of Drd1+ neurons in the anterior insula was twice higher among inhibitory neurons than excitatory neurons. Second, we found that pharmacological activation of D1 in the anterior insula is anxiogenic, suggesting a direct link between insular dopamine signaling and anxiety-related behaviors. Using fiber-photometry recordings, we identified that the amplitude of dopamine release onto D1+ neurons in the anterior insula while mice were in anxiogenic spaces or receiving mild foot shocks was both positively correlated with mice level of trait anxiety. Population dynamics and deep-learning analyses of anterior insula single-unit recordings uncovered distinct coding patterns of anxiety-provoking and safe environments, as well as tastants of positive and negative valence. Remarkably, systemic D1 activation, which heightens anxiety-related behaviors, dampens this coding dichotomy by increasing coding variability for protected spaces while increasing the coding reliability for anxiogenic spaces. Interestingly, the coding reliability of anxiogenic areas was positively correlated with mice level of trait anxiety, and we observed a trend towards a positive correlation between the coding reliability of a negative tastants, and mice level of anxiety. Altogether, our findings provide a new model of neural population coding of anxiety and emotional valence and unravel D1-dependent coding mechanisms in the mouse anterior insula.

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How an anxious heart talks to the brain

Cited by 3 publications

References 10 publications

Abscisic Acid rescues behavior in adult female mice in Attention Deficit Disorder with Hyperactivity model of dopamine depletion by regulating microglia and increasing Vesicular GABA Transporter expression

Abscisic Acid rescues behavior in adult female mice in Attention Deficit Disorder with Hyperactivity model of dopamine depletion by regulating microglia and increasing Vesicular GABA Transporter expression

Abscisic Acid rescues behavior in adult female mice in Attention Deficit Disorder with Hyperactivity model of dopamine depletion by regulating microglia and vesicular GABA transporter

Dopamine transmission in the anterior insula shapes the neural coding of anxiety

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