Inflammatory and anti-inflammatory cytokines bidirectionally modulate amygdala circuits regulating anxiety

Area of Science:

• Neuroimmunology
• Behavioral Neuroscience
• Molecular Psychiatry

Background:

• Peripheral immune molecules, such as cytokines, influence mood and behavior.
• The precise neural circuits through which cytokines impact brain function remain largely unknown.
• Inflammatory episodes in autoimmune or infectious diseases can lead to persistent mood alterations.

Purpose of the Study:

• To investigate how cytokines modulate anxiety-related behaviors.
• To identify specific neural circuits targeted by cytokines in the brain.
• To elucidate the role of cytokine signaling in regulating internal states.

Main Methods:

• Examined the effects of cytokines on neuronal excitability in the basolateral amygdala (BLA).
• Investigated the impact of interleukin-17A (IL-17A), interleukin-17C (IL-17C), and interleukin-10 (IL-10) on BLA neuron function.
• Utilized anti-interleukin-17 receptor A (IL-17RA) antibodies and assessed resulting behavioral changes.

Main Results:

• Cytokines act as neuromodulators, regulating anxiety via receptor-expressing neurons in the BLA.
• Elevated IL-17A and IL-17C levels increased BLA neuron excitability and promoted anxiety.
• Interleukin-10 (IL-10) exerted opposing effects on BLA neuron excitability and behavior.
• Cytokine receptors (IL-17RA/RE and IL-10 receptor) on the same BLA neuron population mediate these effects.

Conclusions:

• Cytokine signaling bidirectionally modulates anxiety through specific BLA neuronal populations.
• Inflammatory and anti-inflammatory cytokines directly impact neural substrates controlling internal states.
• This study highlights a direct mechanism linking peripheral inflammation to altered brain function and behavior.