NPY-mediated synaptic plasticity in the extended amygdala prioritizes feeding during starvation

• Published in: Nature communications 2024-06, Vol.15 (1), p.5439-16, Article 5439
• Main Authors: Dodt, Stephan, Widdershooven, Noah V., Dreisow, Marie-Luise, Weiher, Lisa, Steuernagel, Lukas, Wunderlich, F. Thomas, Brüning, Jens C., Fenselau, Henning
• Format: Article
• Language: English
• Subjects: 631/378/1488/1562; 631/378/2591; 631/378/3920; 64; 64/60; 9/74; Agouti-Related Protein - genetics; Agouti-Related Protein - metabolism; Amygdala; Amygdala - metabolism; Amygdala - physiology; Animals; Anxiety; Anxiety - metabolism; Anxiety - physiopathology; Eating - physiology; Emotional behavior; Fasting; Fasting - physiology; Feeding; Feeding behavior; Feeding Behavior - physiology; Food intake; GABAergic Neurons - metabolism; Humanities and Social Sciences; Hunger; Hunger - physiology; Hypothalamus; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Modulators; multidisciplinary; Neural networks; Neuromodulation; Neuronal Plasticity - physiology; Neurons; Neurons - metabolism; Neurons - physiology; Neuropeptide Y; Neuropeptide Y - genetics; Neuropeptide Y - metabolism; Neuropeptides; Plasticity; Science; Science (multidisciplinary); Septal Nuclei - metabolism; Septal Nuclei - physiology; Starvation; Starvation - metabolism; Stria terminalis; Synaptic plasticity; γ-Aminobutyric acid
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-49766-0

Efficient control of feeding behavior requires the coordinated adjustment of complex motivational and affective neurocircuits. Neuropeptides from energy-sensing hypothalamic neurons are potent feeding modulators, but how these endogenous signals shape relevant circuits remains unclear. Here, we examine how the orexigenic neuropeptide Y (NPY) adapts GABAergic inputs to the bed nucleus of the stria terminalis (BNST). We find that fasting increases synaptic connectivity between agouti-related peptide (AgRP)-expressing ‘hunger’ and BNST neurons, a circuit that promotes feeding. In contrast, GABAergic input from the central amygdala (CeA), an extended amygdala circuit that decreases feeding, is reduced. Activating NPY-expressing AgRP neurons evokes these synaptic adaptations, which are absent in NPY-deficient mice. Moreover, fasting diminishes the ability of CeA projections in the BNST to suppress food intake, and NPY-deficient mice fail to decrease anxiety in order to promote feeding. Thus, AgRP neurons drive input-specific synaptic plasticity, enabling a selective shift in hunger and anxiety signaling during starvation through NPY. Neuropeptides are potent feeding modulators, but how these endogenous signals shape relevant neurocircuits remains unclear. Here, the authors show that hypothalamic neuropeptide Y drives input-specific synaptic plasticity, enabling a selective shift in hunger and anxiety signaling during starvation.