Signal processing in the vagus nerve: Hypotheses based on new genetic and anatomical evidence

Each organism must regulate its internal state in a metabolically efficient way as it interacts in space and time with an ever-changing and only partly predictable world. Success in this endeavor is largely determined by the ongoing communication between brain and body, and the vagus nerve is a crucial structure in that dialogue. In this review, we introduce the novel hypothesis that the afferent vagus nerve is engaged in signal processing rather than just signal relay. New genetic and structural evidence of vagal afferent fiber anatomy motivates two hypotheses: (1) that sensory signals informing on the physiological state of the body compute both spatial and temporal viscerosensory features as they ascend the vagus nerve, following patterns found in other sensory architectures, such as the visual and olfactory systems; and (2) that ascending and descending signals modulate one another, calling into question the strict segregation of sensory and motor signals, respectively. Finally, we discuss several implications of our two hypotheses for understanding the role of viscerosensory signal processing in predictive energy regulation (i.e., allostasis) as well as the role of metabolic signals in memory and in disorders of prediction (e.g., mood disorders). •Recent evidence from the ascending vagus nerve suggests that it integrates and compresses viscerosensory signals as they ascend to the brain.•Rather than a precise viscerotopic map, the nodose ganglion instead maps viscerosensory signals along multiple spatiotemporal gradients.•Evidence from central and peripheral neurons suggests asynaptic signal processing in the form of sensorimotor integration is physiologically plausible in the vagus nerve.•The broader implications of these hypotheses are discussed for interoception, the predictive regulation of energy (i.e., allostasis), and metabolic regulation in memory and disorders of prediction.