Menthol-induced facilitation of cerebrocortical excitatory propagation induced by air puff stimulation of the nasal cavity in the rat: An optical imaging study

Temperature plays a critical role in the sensation of airflow in the nasal mucosa. Neural activities of the ethmoidal nerve, a trigeminal afferent, responding to airflow are suppressed by warm airflow, whereas cold airflow enhances the ethmoidal nerve activities, which is mimicked by application of menthol, a cold-sensitive TRPM8 receptor agonist. However, it has been an open issue how menthol modulates the spatiotemporal profiles of neural activities of somatosensory cortical neurons. In this study, we assessed neural responses to an air puff stimulation (100 ms) to the nasal cavity in the absence or presence of l-menthol using an optical imaging technique with a voltage-sensitive dye in the primary cortex (S1) of urethane-anesthetized rats. A weak air puff application (15 psi) without l-menthol induced neural excitation in a part of the contralateral S1. The air puff stimulation with l-menthol significantly increased the optical signal intensity, expanded the activated area, and shortened the latency, compared to those in the absence of l-menthol. These results suggest that activation of cold-sensitive TRPM8 receptors sharpens airflow sensation in the nasal cavity and expands the receptive field, especially toward the pharynx, which may contribute to enhanced flavor perception.