RETROSPLENIAL CORTEX INVOLVEMENT IN NOVELTY EXPLORATION ALTERATIONS IN A MOUSE MODEL OF AUTISM

The gut-brain axis plays an important role in appetite and metabolic homeostasis. Previous work by Gabanyi et al. (2022) shows that neuronal Nod2 in the brain senses muramyl dipeptide (MDP) from gut bacteria. This pathway contributes to appetite control and thermoregulation. Importantly, it affects specific hypothalamic regions in a sex- and age-dependent manner, with pronounced effects in older female mice.
The main aim of this study is to investigate the basis of the observed sex- and age-specific effects. We hypothesized that sex hormones, particularly estrogens, mediate this bias, as their circulating levels vary substantially between sexes and across age. Estrogens are also well-established regulators of food intake and energy balance, acting predominantly via estrogen receptor α (ERα) in the hypothalamus.
By manipulating circulating hormone levels and ERα expression in hypothalamic neurons, we show that estrogens modulate brain responses to bacterial-derived signals in female mice. Using fluorescent endogenous reporters and viral tracing approaches, we have mapped candidate neuronal populations and circuits involved in this hormone-dependent gut-brain interaction. Future ex vivo electrophysiological experiments will investigate the underlying cellular mechanisms and temporal dynamics of this pathway.
Together, this work will advance our understanding of sex differences in the gut-brain axis and the contribution of sex hormones to its regulation.