Extrahypothalamic GABAergic nociceptin-expressing neurons regulate AgRP neuron activity to control feeding behavior

Area of Science:

• Neuroscience
• Endocrinology
• Behavioral Biology

Background:

• Arcuate nucleus agouti-related peptide (AgRP) neurons are crucial for feeding regulation.
• Feeding behavior is influenced by homeostatic signals, nutrients, and higher brain regions.
• The direct synaptic control of AgRP neurons by higher brain regions remains largely unknown.

Purpose of the Study:

• To investigate whether neurons in higher brain regions directly modulate AgRP neuron activity and feeding behavior.
• To identify the specific neuronal pathways involved in this modulation.

Main Methods:

• Utilized optogenetics and chemogenetics to manipulate neuronal activity.
• Performed in vivo electrophysiology and calcium imaging.
• Used immunohistochemistry and viral tracing to map neuronal connections.
• Investigated the effects of neuronal ablation on feeding and body weight.

Main Results:

• Identified GABAergic nociceptin-expressing neurons in the anterior bed nuclei of the stria terminalis (aBNST) that directly synapse onto AgRP neurons.
• Activation of aBNST nociceptin neurons inhibited AgRP neuron activity and suppressed feeding.
• Increased activity of these aBNST neurons was observed upon food availability.
• Ablation of aBNST nociceptin neurons led to obesity.
• These aBNST neurons receive inputs from various brain regions and hypothalamic nuclei.

Conclusions:

• aBNST GABAergic nociceptin neurons directly inhibit AgRP neurons, playing a significant role in feeding control.
• These neurons integrate homeostatic and nonhomeostatic signals, acting as a gateway to feeding behavior.
• Targeting these neurons could offer new strategies for managing obesity and feeding disorders.