the vagus nerve: a neuroscientist's perspective

polyvagal theory

Modern neuroimaging and electrophysiological studies have shown that vagal activity is related to emotional regulation, resilience to stress, and social engagement. This underlies Stephen Porges' "Polyvagal Theory," which views the vagus nerve as a key mediator of safety, social connection, and threat responses. This theory proposes that the vagus nerve has evolved to include distinct ventral and dorsal pathways associated with different behavioural states: the ventral vagal complex, related to social engagement and calm states, operates through myelinated fibres, enabling rapid response. The dorsal vagal complex, linked to immobilisation responses, uses unmyelinated fibres and represents a more primitive defensive system. Proving vagal tone serves as a biomarker of parasympathetic regulation and adaptability.

why is the vagus nerve so important to neuroscientists?

Neuroscientists are interested in the vagus nerve because of its role in maintaining internal balance (homeostasis), influencing brain health and adaptability (neuroplasticity), mental health and inflammation.

vagus nerve and microbiota

Accumulating evidence suggests that specific gut microbiota exhibit antidepressant-like behavioural effects and can regulate neurogenesis and the expression of brain-derived neurotrophic factor (BDNF) in the hippocampus. The precise mechanisms underlying these effects are not yet clear. However, the vagus nerve is one of the primary bidirectional routes of communication between the gut and the brain and thus may represent a candidate mechanism. Recent findings suggest that vagal nerve activity influences neurogenesis and BDNF mRNA expression in the adult hippocampus. While the gut microbiota can influence brain function through endocrine, immune, and metabolic routes, the vagus nerve is the fastest and most direct neural channel. Afferent fibres detect luminal nutrients in the gut, mechanical stretch, inflammatory mediators, microbial metabolites, and enteroendocrine hormone release (CCK, GLP-1, PYY, serotonin).

Gut microbes can modulate vagal activity through several mechanisms, including their metabolites, which are neurotransmitters produced by bacteria (GABA, serotonin precursors, tryptophan metabolites). Enteroendocrine cells form "neuropods", which are axon-like extensions of the cell that form direct synapses with vagal afferents, allowing the gut to send signals to the brain within milliseconds. It acts like a sensory neuron of the gut, rapidly translating nutrients and microbial metabolites into neural activity. Microbes can change the hormone output of these cells. Immune signals from the gut, such as inflammatory molecules, cytokines and mast-cell mediators, can activate the vagus nerve and trigger the body's anti-inflammatory reflex. Also, the gut microbiota can alter how enteric (gut) neurons fire, thereby affecting the messages they send to the brain via the vagus nerve. The Enteric Nervous System (ENS), often called the "second brain" of the gut, is an extensive network of neurons embedded in the walls of the digestive tract that can operate independently of the brain and spinal cord.

ENS-vagus interactions refer to the continuous communication between the enteric nervous system and the vagus nerve, through which gut activity and signals are relayed to and from the brain. Microbiota modulate the excitability of enteric neurons, altering information sent to vagal afferents. The vagus nerve integrates microbial and metabolic information into autonomic regulation, emotional processing, arousal and homeostasis. This means that microbiota–vagus nerve interactions can modulate stress and anxiety responses, mood and emotional regulation, sleep, and Circadian autonomic balance. It can also influence appetite regulation, as microbiota influence the vagal-microbiota sensing pathways that regulate hormones – ghrelin, GLP-1, leptin sensitivity and reward-related eating patterns. It is shown to affect pain perception/ visceral hypersensitivity/IBS. IBS and functional GI disorders are characterised by altered microbiota composition, vagal afferent sensitisation, and disturbed brain-gut autonomic signalling. In animal studies, sectioning of the vagus nerve prevents many microbiota-induced behavioural effects, which is strong causal evidence.

vagus nerve efferents and microbiota

While "afferent" effects dominate, "efferent vagal" activity also indirectly shapes the microbiota, impacting gastrointestinal motility, acid secretion and bile flow, mucosal immune regulation, and the anti-inflammatory reflex (cholinergic anti-inflammatory pathway, thereby proving that vagal tone influences microbial ecology.

vagus nerve and inflammation

The vagus nerve is a key regulator of inflammation through the "cholinergic anti-inflammatory reflex," where vagal "afferents" sense immune signals and vagal "efferents" suppress cytokine release from macrophages via acetylcholine acting on α7-nicotinic receptors. Gut microbiota, immune mediators, and ENS activity all influence vagal firing and therefore the strength of this anti-inflammatory control. Low vagal tone (typically reflected by low HRV) is associated with higher systemic inflammation, while stimulating the vagus (via VNS, slow breathing, meditation, cold exposure, or exercise) enhances parasympathetic output and helps reduce excessive inflammatory responses.

NTS-LC/PFC communication

This refers to the information flow from the "Nucleus Tractus Solitarius" (NTS) to the "Locus Coeruleus" (LC) to the Prefrontal Cortex (PFC). This is one of the most essential autonomic, cognitive, and emotional pathways in the brain. NTS–LC/PFC communication is the neural pathway through which vagal signals from the body influence arousal, mood, attention, and executive control in the cortex. Dysregulation of NTS–LC/PFC communication disrupts the brain's control of stress, attention, and autonomic balance, contributing to conditions such as anxiety, PTSD, depression, ADHD, chronic stress, IBS, Parkinson's disease, and sleep disorders. In essence, when this vagal–noradrenergic–prefrontal pathway malfunctions, both emotional regulation and bodily homeostasis become unstable. It is also a key mechanism behind VNS therapy, meditation and breathwork, interoception-based treatments, and microbiota-modulating interventions.

clinical context

Research suggests interactions relevant to depression and anxiety, IBS / functional dyspepsia, metabolic syndrome, Parkinson's disease prodrome (gut-first hypothesis; α-syn propagation via vagus), sleep disorders and vagal imbalance. The idea that misfolded α-synuclein might travel from gut to brain via the vagus (Braak's hypothesis) has strong experimental support in rodents and mixed evidence in humans. According to Braak's hypothesis, an unknown pathogen (virus or bacterium) in the gut could be responsible for Parkinson's disease (PD) originating in the gastrointestinal (GI) tract, and similar associations have been established for Alzheimer's disease (AD) and cerebrovascular diseases (CVD).

approaches to nervous system care: how to assess vagal tone

Vagal tone refers to the activity level of the vagus nerve and is measured by the gold standard of systems, including:

• Heart rate variability (HRV). Higher HRV generally indicates better vagal function and resilience.
• Respiratory Sinus Arrhythmia (RSA). This is the natural increase in heart rate during inhalation and decrease during exhalation. The strength of this rhythm reflects vagal control over the heart.
• Biomarker analysis: inflammatory markers (IL-6), stress hormones (cortisol), gastric function (IBS, reflux)
• Behavioural & Cognitive Assessments: Questionnaires on mood, anxiety, digestive health, and social engagement provide context for the objective data. The vagus nerve is heavily implicated in social connection and emotional regulation, as described in "Polyvagal Theory".