Friday, May 9, 2025
5/9/2025
Neural circuitry mediating lactation-induced hyperphagia - Energy homeostasis is controlled by neural circuits which sense changes in energy demands to maintain body weight at a stable set point. Although body weight is remarkably stable in mammals, females must temporarily increase their energy intake during pregnancy and lactation to accommodate the massive energy demands associated with reproduction. During lactation, mice increase their food intake by 300- 400 percent, and similar changes in energy intake occur in humans during lactation. These adaptive changes are critical for the long-term health of the mother and child, as excessive or insufficient energy intake during lactation increases the subsequent risk of both the mother and child developing metabolic and psychiatric disorders later in life. This is especially apparent during lactation since critical feeding and motivational circuitry do not fully develop until the end of the lactation period in mice, and alterations in energy intake during this period result in long-lasting perturbations in metabolic, reward, and motivational circuitry. Therefore, it is of paramount importance to human health to determine the mechanism(s) mediating the elevated food intake associated with lactation. Although hypothalamic hunger circuitry, hindbrain satiety circuits, and reward based feeding circuitry are critical for normal feeding behavior, it remains unclear how these circuits are altered during lactation. Further, the neural circuitry and molecular mechanism(s) mediating the hyperphagia of lactation are unknown. We hypothesize that lactation results in widespread functional changes in hypothalamic, hindbrain, and midbrain reward circuitry, which together act to promote feeding during lactation. In this proposal we will leverage recent advances in neural circuit manipulation, single nuclei transcriptomics, and in vivo imaging approaches to determine the functional neuroanatomy mediating increased feeding during lactation in mice. Together these studies will provide the foundation for therapeutic strategies aiming to improve the metabolic health of both the mother and child, while uncovering fundamental differences in the neural circuitry regulating feeding between the sexes.
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