Cortical and Sensory Integration in Brainstem Circuits for Mastication

Mastication is a vital function that relies on precise synchronization among multiple brainstem regions, known as being part of a central pattern generator (CPG). Movements can be triggered either by stimulating a sensory-motor region called the cortical masticatory area (CMA), well-documented in various species but not yet formally identified in mice, or by stimulating the orofacial sensory primary afferents, the fibers of which form the trigeminal tract (Vtr). However, it is unclear whether these different inputs activate distinct components of the CPG or converge on the same. This study aims to map the brainstem areas activated by cortical and sensory inputs using immunohistochemistry against the cellular activity markers, c-Fos and Ca²⁺ imaging, respectively. Optogenetic stimulation of the cortical masticatory area in awake, head-fixed mice reliably induced rhythmic jaw movements and increased c-Fos expression in multiple brainstem regions, with the strongest activation in the peritrigeminal area (PeriV). In contrast, in vitro electrical stimulation of the Vtr predominantly activated neurons and astrocytes in the main sensory nucleus (NVsnpr), the dorsal area of PeriV adjacent to it, and the parvocellular reticular nucleus (PCRt). The areas containing the highest numbers of activated cells differed clearly according to the type of inputs and overlapped only in the PCRt, ventral and slightly medial to the trigeminal motor nucleus and the most dorsomedial part of PeriV. These findings demonstrate that cortical and sensory inputs take part in distinct components of the brainstem masticatory circuitry, with PCRt emerging as a potential point of convergence and providing new insights into the components of the CPG of mastication.