Enteric nervous system electrophysiology

Vitamin D deficiency is prevalent in adults and is associated with cognitive impairment. However, the mechanism by which adult vitamin D (AVD) deficiency affects cognitive function remains unclear. We examined spatial memory impairment in AVD-deficient BALB/c mice and its underlying mechanism by measuring spine density, long term potentiation (LTP), nitric oxide (NO), neuronal nitric oxide synthase (nNOS), and endothelial NOS (eNOS) in the hippocampus. Adult male BALB/c mice were fed a control or vitamin D deficient diet for 20 weeks...

GABAA receptors containing the α 6 subunit are highly expressed in cerebellar granule cells and less abundantly in many other neuronal and peripheral tissues. Here, we for the first time summarize their importance for the functions of the cerebellum and the nervous system. The cerebellum is not only involved in motor control but also in cognitive, emotional, and social behaviors. α 6 βγ 2 GABAA receptors located at cerebellar Golgi cell/granule cell synapses enhance the precision of inputs required for cerebellar timing of motor activity and are thus involved in cognitive processing and adequate responses to our environment...

The microbiome influences the emotional and cognitive phenotype of its host, as well as the neurodevelopment and pathophysiology of various brain processes and disorders, via the well-established microbiome-gut-brain axis. Rapidly accumulating data link the microbiome to severe neuropsychiatric disorders in humans, including schizophrenia, Alzheimer's and Parkinson's. Moreover, preclinical work has shown that perturbation of the microbiome is closely associated with social, cognitive and behavioural deficits...

INTRODUCTION: Gastric electrical stimulation (GES) has been recommended for drug refractory patients with gastroparesis, but no clear baseline predictors of symptom response exist. We hypothesized that long-term predictors to GES for foregut and hindgut symptoms exist, particularly when using augmented energies. PATIENTS: We evaluated 307 patients at baseline, 1 week post temporary GES, and one year after permanent GES. Baseline measures included upper and lower symptoms by patient-reported outcomes (PRO), solid and liquid gastric emptying (GET), cutaneous, mucosal, and serosal electrophysiology (EGG, m/s EG), BMI, and response to temporary stimulation...

How the Enteric Nervous System (ENS) coordinates propulsion of content along the gastrointestinal (GI)-tract has been a major unresolved issue. We reveal a mechanism that explains how ENS activity underlies propulsion of content along the colon. We used a recently developed high-resolution video imaging approach with concurrent electrophysiological recordings from smooth muscle, during fluid propulsion. Recordings showed pulsatile firing of excitatory and inhibitory neuromuscular inputs not only in proximal colon, but also distal colon, long before the propagating contraction invades the distal region...

In the enteric nervous system, there exist a huge number of local intrinsic neurons, which control the gastrointestinal functions. Culture of enteric neurons provides a good model system for physiological, electrophysiological, and pharmacological studies. Here, we describe two methods to obtain sufficient enteric neurons from mouse myenteric plexuses by directly culturing primary neurons or inducing neuronal differentiation of enteric neural stem/progenitor cells.

Cardiovascular malformations during embryogenesis can lead the inferior laryngeal nerve to branching directly from the cervical vagus nerve and entering the larynx. This rare anatomical variation is known as a non-recurrent inferior laryngeal nerve (NRILN), and increases the risk of accidental injury resulting in postoperative vocal cord paralysis during neck surgery. We report a case of an 83-year-old man who presented with left symptomatic internal carotid artery stenosis with a right-sided aortic arch and aberrant left subclavian artery (ALSCA)...

BACKGROUND: The pro-inflammatory cytokine, interleukin (IL)-6 is elevated in individuals with the functional bowel disorder, irritable bowel syndrome (IBS). IL-6 can independently modify intestinal secreto-motor function, thereby contributing to IBS pathophysiology. Additionally, hormonal changes may underlie symptom flares. Post-prandial exacerbation of IBS symptoms has been linked to secretion of the incretin hormone, glucagon-like peptide-1 (GLP-1), which can also influence colonic secreto-motor activity...

BACKGROUND: Functional dyspepsia (FD) is a common gastroduodenal disorder, yet its pathophysiology remains poorly understood. Bioelectrical gastric slow-wave abnormalities are thought to contribute to its multifactorial pathophysiology. Electrogastrography (EGG) has been used to record gastric electrical activity; however, the clinical associations require further evaluation. AIMS: This study aimed to systematically assess the clinical associations of EGG in FD...

Glutamate transporter proteins, expressed on both neurons and glia, serve as the main gatekeepers that dictate the spatial and temporal actions of extracellular glutamate. Glutamate is essential to the function of the healthy brain yet paradoxically contributes to the toxicity associated with many neurodegenerative diseases. Rapid transporter-mediated glutamate uptake, primarily occurring at astrocytic processes, tightens the efficiency of excitatory network activity and prevents toxic glutamate build-up in the extracellular space...

Fast excitatory synaptic transmission in the central nervous system relies on the AMPA-type glutamate receptor (AMPAR). This receptor incorporates a nonselective cation channel, which is opened by the binding of glutamate. Although the open pore structure has recently became available from cryo-electron microscopy (Cryo-EM), the molecular mechanisms governing cation permeability in AMPA receptors are not understood. Here, we combined microsecond molecular dynamic (MD) simulations on a putative open-state structure of GluA2 with electrophysiology on cloned channels to elucidate ion permeation mechanisms...

BACKGROUND: Gastric motility disorders, which include both functional and organic etiologies, are highly prevalent. However, there remains a critical lack of objective biomarkers to guide efficient diagnostics and personalized therapies. Bioelectrical activity plays a fundamental role in coordinating gastric function and has been investigated as a contributing mechanism to gastric dysmotility and sensory dysfunction for a century. However, conventional electrogastrography (EGG) has not achieved common clinical adoption due to its perceived limited diagnostic capability and inability to impact clinical care...

BACKGROUND: Chronic nausea in adolescents with functional gastrointestinal disorders is an increasingly reported but poorly understood symptom that negatively affects quality of life. Functional gastrointestinal disorders are known to correlate closely with slow wave rhythm disturbances. The ability to characterize gastric electrophysiologic perturbations in functional nausea patients could provide potential diagnostic and therapeutic tools for nausea patients. METHODS: We used high-resolution electrogastrograms (HR-EGG) to measure gastric slow wave parameters in pediatric chronic nausea patients and healthy subjects both pre- and postprandial...

BACKGROUND: The gut is the only organ system with intrinsic neural reflexes. Intrinsic primary afferent neurons (IPANs) of the enteric nervous system initiate intrinsic reflexes, form gut-brain connections, and undergo considerable neuroplasticity to cause digestive diseases. They remain inaccessible to study in mice in the absence of a selective marker. Advillin is used as a marker for primary afferent neurons in dorsal root ganglia. The aim of this study was to test the hypothesis that advillin is expressed in IPANs of the mouse jejunum...

BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder thought to be caused by accumulation of α-synuclein (α-syn) within the brain, autonomic nerves, and the enteric nervous system (ENS). Involvement of the ENS in PD often precedes the onset of the classic motor signs of PD by many years at a time when severe constipation represents a major morbidity. Studies conducted in vitro and in vivo, have shown that squalamine, a zwitterionic amphipathic aminosterol, originally isolated from the liver of the dogfish shark, effectively displaces membrane-bound α-syn...

The autonomic nervous system (ANS) regulates tissue homeostasis and remodelling through antagonistic effects of noradrenergic sympathetic and cholinergic parasympathetic signalling. Despite numerous reports on the induction of sympathetic neurons from human pluripotent stem cells (hPSCs), no induction methods have effectively derived cholinergic parasympathetic neurons from hPSCs. Considering the antagonistic effects of noradrenergic and cholinergic inputs on target organs, both sympathetic and parasympathetic neurons are expected to be induced...

Ulcerative colitis (UC) and Crohn's disease (CD) are pathological conditions with an unknown aetiology that are characterised by severe inflammation of the intestinal tract and collectively referred to as inflammatory bowel disease (IBD). Current treatments are mostly ineffective due to their limited efficacy or toxicity, necessitating surgical resection of the affected bowel. The management of IBD is hindered by a lack of prognostic markers for clinical inflammatory relapse. Intestinal inflammation associates with the infiltration of immune cells (leukocytes) into, or surrounding the neuronal ganglia of the enteric nervous system (ENS) termed plexitis or ganglionitis...

The brain-gut axis which is an interaction between recognition and emotion and the gut sensory system for food and microbiota is important for health. However, there is no real-time monitoring system of the brain and the gut simultaneously so far. We attempted to establish a dual real-time monitoring system for the brain-gut axis by a combination of intravital Ca2+ imaging of the gut and electroencephalogram. Using a conditional Yellow Cameleon 3.60 expression mouse line, we performed intravital imaging of the gut, electrophysiological recordings of the vagus nerve, and electroencephalogram recordings of the various cortical regions simultaneously upon capsaicin stimuli as a positive control...

Parkinson's disease (PD) is predominantly idiopathic in origin, and a large body of evidence indicates that gastrointestinal (GI) dysfunctions are a significant comorbid clinical feature; these dysfunctions include dysphagia, nausea, delayed gastric emptying, and severe constipation, all of which occur commonly before the onset of the well-known motor symptoms of PD. Based on a distinct distribution pattern of Lewy bodies (LB) in the enteric nervous system (ENS) and in the preganglionic neurons of the dorsal motor nucleus of the vagus (DMV), and together with the early onset of GI symptoms, it was suggested that idiopathic PD begins in the ENS and spreads to the central nervous system (CNS), reaching the DMV and the substantia nigra pars compacta (SNpc)...

Background: Gastrointestinal dysfunction can affect Parkinson's disease (PD) patients long before the onset of motor symptoms. However, little is known about the relationship between gastrointestinal abnormalities and the development of PD. Contrary to other animal models, the human A53T alpha-synuclein (αS) transgenic mice, Line G2-3, develops αS-driven neurological and motor impairments after 9 months of age, displaying a long presymptomatic phase free of central nervous system (CNS) dysfunction...