Isl1⁺ Central Amygdala Neurons Coordinate Control of the Jaw and Stomach During Ingestion

Central Amygdala neurons expressing Isl1 (CeA^Isl1+) project to brainstem regions involved in control of the jaw and the stomach, including the parabrachial nucleus (PBN), the nucleus of the tractus solitary (NTS), and the parvocellular reticular nucleus (PCRt). Stimulation of CeA^Isl1+ cells elicits fictive feeding, particularly biting. Activation of these neurons can rate dependently set the amplitude of bite force and inhibition dramatically reduces bite force. Findings suggest this force generation depends on modulation of a jaw closing reflex involving tooth sensory neurons in the mesencephalic trigeminal nucleus (Me5). Anatomical tracing studies show Me5 neurons receive synaptic input from CeA^Isl1+ neurons. Patch clamp recordings of Me5 neurons indicate this synapse is mediated by GABA yet depolarizing. Activation of CeA^Isl1+ neurons is capable of dramatically potentiating the periodontal jaw closing reflex, a reflex whereby Me5 tooth sensory neurons activate jaw closing muscles. In addition to controlling the actions of the jaw, CeA^Isl1+ neuron stimulation is sufficient to reduce gastric pH. Inhibition experiments show these cells are necessary for lowering gastric pH in mice anticipating a meal. Finally, CeA^Isl1+ neurons can modulate gastric motility, stimulation transiently suppresses gastric motility, an effect also observed when animals chewed food. Subdiaphragmatic vagotomy eliminated the transient suppression of gastric motility otherwise observed with CeA^Isl1+ neuron stimulation or food chewing. Taken together, this molecularly and anatomically defined population generates specific motor patterns of ingestion that involve not only release of oromotor patterns, but also modulation of gastric functions.