From Molecules to Function: The World of Mesencephalic Trigeminal Nucleus Neurons in Health and Disease

Among all the primary sensory neurons, those innervating muscle spindles in the jaw-closing muscles are exceptionally located in the brainstem as the mesencephalic trigeminal nucleus (MTN), thereby exceptionally receiving various synaptic inputs from higher brain regions onto various receptors, including glutamate and adrenergic receptors. Usually, the proprioceptive primary sensory neuron is involved in the regulation of voluntary isometric muscle contraction. However, MTN neurons are involved not only in such regulation but also in malocclusion-induced anxiety or stress, presumably because of various synaptic inputs arising from higher brain regions onto MTN neurons. It is noteworthy that anxiety or stress is often accompanied by bruxism while normal mastication can promote coping with stress. Furthermore, chronic malocclusion-induced anxiety or stress may further develop into Alzheimer-type dementia, suggesting an involvement of MTN neurons in the pathogenesis of such dementia.

In view of recent progress in this research area, it should be noted that MTN neurons can function in two different modes: one as the primary sensory neurons for faithfully relaying the impulses arising from sensory organs to the jaw-closing motoneurons (JCMNs) and the other as the premotor neurons for driving the JCMNs independently of muscle spindle activity. The two functional modes of MTN neurons may be able to account for the multiple involvements of MTN neurons in malocclusion-induced stress and stress-induced bruxism.

Therefore, it is now critical to integrate findings on ion channels, receptors, and neuromodulators in terms of their involvement in transitioning between the two functional modes of MTN neurons—serving as both primary sensory neurons and premotor neurons. This integration should encompass the study of various signaling molecules, such as glutamatergic, adrenergic, and other neuromodulatory systems, that may influence these switches in activity mode. Additionally, there is a growing need to explore how these molecular mechanisms interact with broader neural networks. Understanding the circuits that either activate or are modulated by MTN neurons is crucial to fully grasp their diverse functional roles, which span motor control, sensory processing, stress response, and potentially, neurodegenerative pathways.

In this Research Topic, we aim to focus on the molecular, morphological, and electrophysiological characteristics of MTN neurons and their interactions with neural circuits, expanding the study to include their roles in sensory-motor coordination, stress-induced behaviors, and cognitive outcomes. We seek contributions that provide insights into MTN neurons’ involvement in both healthy physiological processes and pathologies such as bruxism, malocclusion, and dementia.