Respiratory-Limbic Coupling via a Thalamic Circuit Alleviates Anxiety

Area of Science:

• Neuroscience
• Respiratory Physiology
• Affective Science

Background:

• Breathing patterns influence emotional states, but the neural mechanisms are not fully understood.
• Existing research highlights the connection between respiration and emotion, yet specific pathways remain elusive.

Purpose of the Study:

• To identify and characterize the neural circuit linking respiratory control to affective states.
• To elucidate the role of the preBötzinger complex (preBötC) to amygdala pathway in anxiety and respiratory regulation.

Main Methods:

• Utilized optogenetics and chemogenetics in male mice to manipulate neuronal activity within the preBötC→paraventricular thalamic nucleus (PVT)→central amygdala (CeA) circuit.
• Recorded respiratory frequency variability and anxiety-like behaviors in response to circuit stimulation or inhibition.
• Investigated the role of PVT projections to the CeA and their impact on amygdala neuronal activity.
• Translated findings to human participants, assessing the effects of slow breathing on anxiety and amygdala oscillations in healthy individuals and epilepsy patients.

Main Results:

• Activation of the preBötC→PVT circuit reduced anxiety and respiratory variability in mice.
• Inhibition of this circuit exacerbated anxiety and respiratory dysfunction.
• The anxiolytic effects were dependent on PVT neurons projecting to the CeA, which modulated amygdala output.
• Volitional slow breathing decreased anxiety in humans and suppressed anxiety-related brain oscillations in the amygdala.

Conclusions:

• A conserved neural circuit involving the preBötC, PVT, and CeA mediates the bidirectional relationship between breathing and affective states.
• Controlled breathing exerts anxiolytic effects through this respiratory-limbic pathway.
• This research provides a mechanistic explanation for the therapeutic benefits of controlled breathing techniques in managing anxiety.