Central amygdala Isl1 neurons control biting by integrating sensory and motivational signals

Summary Efficient orofacial motor control is essential for adaptive interactions with the environment, yet the neural substrates that regulate the force and precision of biting remain poorly understood. Here, we identify a subpopulation of neurons in the central amygdala (CeA) expressing the transcription factor Isl1 (CeA Isl1 ) that plays a crucial role in modulating biting behavior in mice. In vivo calcium imaging revealed that CeA Isl1 neurons are robustly activated at the onset of biting across materials of varying physical properties, with distinct neuronal ensembles selectively encoding responses to the physical properties of the objects. CeA Isl1 neuronal activity scales positively with the hardness of the object, suggesting a role in force modulation. Optogenetic activation of CeA Isl1 neurons enhances biting behavior toward edible or non-edible objects, induces fictive feeding in the absence of physical targets and exerts a reinforcing effect on behavior, whereas inhibition of CeA Isl1 neurons impaired efficient biting of solid food by reducing jaw-closing muscle activity. Projection-specific manipulations revealed that activation of CeA Isl1 projections to the parvocellular reticular formation (PCRt) and pedunculopontine tegmental nucleus (PPtg) increased the duration and frequency of biting, with CeA Isl1 -to-PPTg stimulation producing a positive motivational valence. These findings uncover a previously unrecognized sensorimotor function of the central amygdala in calibrating bite force and precision, linking motivational states to skilled motor output.