Spinal afferent endings in the gastrointestinal tract

Communication between the gastrointestinal tract and the central nervous system, known as the gut-brain axis, is fundamental to physiology and is implicated in a range of pathological conditions. A critical component of this axis is the sensory information conveyed from the gut to the brain through spinal afferent pathways. Understanding the location and types of spinal afferents present in the GI tract and their mechanisms of activation is essential to advance our knowledge of gut-brain communication in health and disease. Though generally trailing knowledge of gut vagal afferents, major advances have been made in understanding spinal sensory pathways through recent critical adaptations of neuroanatomical tracing, neurogenetics and molecular profiling techniques, revealing an unforeseen diversity in the morphology of their endings in the gut wall and novel classifications based on molecular identity. Moreover, spinal afferents have been implicated in multiple physiological functions besides their well-known role in nociception, including potential roles in nutrient sensing and regulating gut motility. Among spinal afferent endings in the gut mucosal layer, much has been learnt about how enterochromaffin (EC) cells communicate with spinal (and vagal) afferents. Evidence now suggests that EC cells release substances (like serotonin), which activate the terminals of spinal (and vagal) afferent endings via a paracrine, not synaptic, transmission. Here, we review the latest findings regarding spinal afferent endings and point to outstanding questions and future directions for research into this complex and clinically relevant area of neuroscience.