Metaplastic neuronal state transition regulates species-specific interoceptive processing in Drosophila

Abstract

Interoceptive processing, which involves the sensing and integration of internal physiological states, is fundamental to maintaining homeostasis. However, how species-specific interoceptive features arise from the underlying biophysical properties of neural circuit physiology remains unclear. We investigate the biophysical basis of species-specific interoception by examining protein-hunger dopamine neurons (DA-WED) in two Drosophila species with divergent dietary ecologies. We find that DA-WED neurons in D. melanogaster exhibit weak persistence of internal states, enabling flexible behavioral transitions during nutrient stress. In contrast, D. sechellia shows strong state persistence, locking neurons into a "preferred" configuration during protein deprivation. This divergence is supported by distinct intrinsic membrane properties, including protein deprivation-induced rebound spikes unique to D. sechellia. Analysis of synaptic dynamics and cardiomyocyte electrophysiology reveals species-specific physiological regulations coordinating central and peripheral systems. Behavioral assays confirm corresponding differences in protein consumption strategies, directly linking neural state geometry to ecologically relevant feeding behavior. Our findings establish metaplastic regulation of neural state transitions as a fundamental mechanism through which ecological specialization shapes interoceptive processing and brain-body coordination. Significance StatementWe identify physiological regulations of neural state transitions as a core mechanism underlying species-specific interoceptive processing. Through comparative electrophysiology in D. melanogaster and D. sechellia, we demonstrate that ecological specialization manifests through distinct intrinsic membrane properties of DA-WED neurons, fundamentally altering neural state space geometry during protein deprivation. Species-specific synaptic plasticity gates these transitions while coupling cardiac rhythms to central computation. Our findings reveal how evolution transforms nutrient sensing into divergent neural dynamics, establishing a mechanistic framework for understanding how ecological pressures sculpt the biophysical architecture of interoceptive circuits to coordinate adaptive brain-body interactions.