scholarly journals Identification of SSRI-evoked antidepressant sensory signals by decoding vagus nerve activity

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Christine L. West ◽  
Karen-Anne McVey Neufeld ◽  
Yu-Kang Mao ◽  
Andrew M. Stanisz ◽  
Paul Forsythe ◽  
...  
Keyword(s):  
Vagus Nerve ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Ex Vivo ◽  
Specific Information ◽  
Neural Firing ◽  
Neural Responses ◽  
Spike Burst ◽  
Neural Firing Pattern ◽  
Mouse Small Intestine ◽  
Preclinical Animal Models

AbstractThe vagus nerve relays mood-altering signals originating in the gut lumen to the brain. In mice, an intact vagus is required to mediate the behavioural effects of both intraluminally applied selective serotonin reuptake inhibitors and a strain of Lactobacillus with antidepressant-like activity. Similarly, the prodepressant effect of lipopolysaccharide is vagus nerve dependent. Single vagal fibres are broadly tuned to respond by excitation to both anti- and prodepressant agents, but it remains unclear how neural responses encode behaviour-specific information. Here we demonstrate using ex vivo experiments that for single vagal fibres within the mesenteric neurovascular bundle supplying the mouse small intestine, a unique neural firing pattern code is common to both chemical and bacterial vagus-dependent antidepressant luminal stimuli. This code is qualitatively and statistically discernible from that evoked by lipopolysaccharide, a non-vagus-dependent antidepressant or control non-antidepressant Lactobacillus strain and are not affected by sex status. We found that all vagus dependent antidepressants evoked a decrease in mean spike interval, increase in spike burst duration, decrease in gap duration between bursts and increase in intra-burst spike intervals. Our results offer a novel neuronal electrical perspective as one explanation for mechanisms of action of gut-derived vagal dependent antidepressants. We expect that our ex vivo individual vagal fibre recording model will improve the design and operation of new, extant electroceutical vagal stimulation devices currently used to treat major depression. Furthermore, use of this vagal antidepressant code should provide a valuable screening tool for novel potential oral antidepressant candidates in preclinical animal models.

scholarly journals Effect of Fluoxetine and Paroxetine on Intestinal Motility in Presence of Ondansetron in ex-vivo Model

2020 ◽  
Vol 1 (3) ◽  
pp. 5
Author(s):  
Ayesha Afzal ◽  
Ammara Khan ◽  
Khalida Ajmal ◽  
Abeera Sikandar ◽  
Saima Rafiqu ◽  
...  
Keyword(s):  
Intestinal Motility ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Contractile Response ◽  
Ex Vivo ◽  
Ex Vivo Model ◽  
Rabbit Ileum ◽  
Medical College ◽  
Fixed Concentration ◽  
Antidepressant Effects

Objective: To understand the effects of fluoxetine and paroxetine with ondansetron on the intestinal motility of rabbit ileum. Study Design: Observational study. Place and Duration of Study: The study was conducted from March to April 2018 in a multidisciplinary lab of Army Medical College, Rawalpindi.Materials and Methods: The contractile effect of intestinal motility was recorded in the power lab. Subjects were twenty four healthy rabbits (Oryctolagus Cuniculus). Semi log dose-response curve was constructed for increasing concentrations of serotonin, ondansetron, fluoxetine, and paroxetine (10-9 to 10-6 M) alone and then in the presence of a fixed concentration of ondansetron (10-6 M) to observe the modulatory role of ondansetron. The serotonin mediated contractions were taken as control.Results: Ondansetron and serotonin caused an increase in the contractile response of rabbits ileum. A depressive response was observed when the contractions were recorded with increased concentration of fluoxetine and paroxetine in the presence of ondansetron. Conclusion: Ondansetron when used concomitantly with selective serotonin reuptake inhibitors(SSRIs), abolishes their antidepressant effects by causing a decrease in the intestinal motility of rabbit ileum.

scholarly journals Peripheral immune cell reactivity and neural response to reward in patients with depression and anhedonia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sara Costi ◽  
Laurel S. Morris ◽  
Abigail Collins ◽  
Nicolas F. Fernandez ◽  
Manishkumar Patel ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Immune Cell ◽  
Ex Vivo ◽  
Flanker Task ◽  
Reward Processing ◽  
Neural Responses ◽  
Depressed Patients ◽  
Reward Anticipation ◽  
Peripheral Leukocytes ◽  
Immune Score

AbstractIncreased levels of peripheral cytokines have been previously associated with depression in preclinical and clinical research. Although the precise nature of peripheral immune dysfunction in depression remains unclear, evidence from animal studies points towards a dysregulated response of peripheral leukocytes as a risk factor for stress susceptibility. This study examined dynamic release of inflammatory blood factors from peripheral blood mononuclear cells (PBMC) in depressed patients and associations with neural and behavioral measures of reward processing. Thirty unmedicated patients meeting criteria for unipolar depressive disorder and 21 healthy control volunteers were enrolled. PBMCs were isolated from whole blood and stimulated ex vivo with lipopolysaccharide (LPS). Olink multiplex assay was used to analyze a large panel of inflammatory proteins. Participants completed functional magnetic resonance imaging with an incentive flanker task to probe neural responses to reward anticipation, as well as clinical measures of anhedonia and pleasure including the Temporal Experience of Pleasure Scale (TEPS) and the Snaith-Hamilton Pleasure Scale (SHAPS). LPS stimulation revealed larger increases in immune factors in depressed compared to healthy subjects using an aggregate immune score (t49 = 2.83, p = 0.007). Higher peripheral immune score was associated with reduced neural responses to reward anticipation within the ventral striatum (VS) (r = −0.39, p = 0.01), and with reduced anticipation of pleasure as measured with the TEPS anticipatory sub-score (r = −0.318, p = 0.023). Our study provides new evidence suggesting that dynamic hyper-reactivity of peripheral leukocytes in depressed patients is associated with blunted activation of the brain reward system and lower subjective anticipation of pleasure.

scholarly journals Oral selective serotonin reuptake inhibitors activate vagus nerve dependent gut-brain signalling

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Karen-Anne McVey Neufeld ◽  
John Bienenstock ◽  
Aadil Bharwani ◽  
Kevin Champagne-Jorgensen ◽  
YuKang Mao ◽  
...  
Keyword(s):  
Vagus Nerve ◽  
Serotonin Reuptake ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Tail Suspension Test ◽  
Afferent Neurons ◽  
Tail Suspension ◽  
Primary Afferent Neurons ◽  
Primary Afferent ◽  
Nerve Recordings ◽  
Suspension Test

Abstract The vagus nerve can transmit signals to the brain resulting in a reduction in depressive behavior as evidenced by the long-term beneficial effects of electrical stimulation of the vagus in patients with intractable depression. The vagus is the major neural connection between gut and brain, and we have previously shown that ingestion of beneficial bacteria modulates behaviour and brain neurochemistry via this pathway. Given the high levels of serotonin in the gut, we considered if gut-brain signaling, and specifically the vagal pathway, might contribute to the therapeutic effect of oral selective serotonin reuptake inhibitors (SSRI). Mesenteric nerve recordings were conducted in mice after treatment with SSRI to ascertain if this class of drugs resulted in increased vagal excitability. Patch clamp recordings of enteric neurons were carried out to measure activity of primary afferent neurons in the gut in response to SSRI and to assess the importance of gut epithelium in transducing signal. The tail suspension test (TST) was used following 14d feeding of SSRI in vagotomised and surgical sham mice to measure depressive-like behaviour. Brain mRNA expression was examined via PCR and the intestinal microbiome was assessed. Mesenteric nerve recordings in BALB/c mice demonstrated that oral treatment with SSRI leads to a significant increase in vagal activity. This effect was not observed in mice treated with a representative noradrenaline-dopamine reuptake inhibitor. It is known that signals from the gut can be transmitted to the vagus via the enteric nervous system. Exposure of the gut to SSRI increased the excitability of intrinsic primary afferent neurons in the myenteric plexus, through an intestinal epithelium dependent mechanism, and alpha-diversity of gut microbiota was altered. Critically, blocking vagal signaling from gut to brain, via subdiaphragmatic vagotomy, abolished the antidepressive effects of oral SSRI treatment as determined by the tail suspension test. This work suggests that vagus nerve dependent gut-brain signaling contributes to the effects of oral SSRI and further, highlights the potential for pharmacological approaches to treatment of mood disorders that focus on vagal stimulation and may not even require therapeutic agents to enter the circulation.

Neural correlates of nystagmus in abducens nerve

1979 ◽  
Vol 42 (5) ◽  
pp. 1282-1296 ◽  
Author(s):  
V. Honrubia ◽  
D. B. Reingold ◽  
C. G. Lau ◽  
P. H. Ward
Keyword(s):  
Low Frequency ◽  
Abducens Nerve ◽  
Head Rotation ◽  
Phase Lag ◽  
Neural Firing ◽  
Neural Responses ◽  
Firing Rates ◽  
Viscous Forces ◽  
Phase Angle Difference ◽  
Phase Lead

1. The firing rates of action potentials of abducens nerve single fibers were recorded in the cat's orbit during a variety of vestibular and optokinetic stimulations. 2. Comparison was made of the neural firing rates associated with agonist and antagonist responses during slow and fast components of vestibular and optokinetic nystagmus. It was found that the relationship between the motoneuron firing rates and the eye motion was independent of the reflex with which they were associated--vestibular or optokinetic, or the type of response--agonist or antagonist. No neurons were observed that responded only during the fast or only during the slow nystagmus phase. Motoneuron firing rates were proportional to both velocity and position of the eye in a ratio of 1 (spikes/s)/(deg/s) to 7.2 (spikes/s)/deg. The behavior of the motoneurons was compatible with the hypothesis that thier firing rates are sufficient to overcome both elastic and viscous forces by which the muscles and ligaments hold the eye in the orbit. 3. For low-frequency head rotations, eye displacement and neural responses showed a small phase angle difference. At higher frequencies, however, while the eyes maintained a fixed relationship to the head rotation, the neural responses showed an increasing phase lead. One component of this phase lead compensated for the phase lag introduced by the orbital mechanics. The other was modeled as a constant delay of approximately 70 ms, which may be accounted for by neuromuscular transmission and transduction.

scholarly journals Ratiometric analysis using Raman spectroscopy as a powerful predictor of structural properties of fatty acids

2018 ◽  
Vol 5 (12) ◽  
pp. 181483 ◽  
Author(s):  
Lauren E. Jamieson ◽  
Angela Li ◽  
Karen Faulds ◽  
Duncan Graham
Keyword(s):  
Fatty Acids ◽  
Raman Spectroscopy ◽  
Biological Sample ◽  
Ex Vivo ◽  
Degree Of Saturation ◽  
Specific Information ◽  
Analytical Technique ◽  
Starting Point

Raman spectroscopy has been used extensively for the analysis of biological samples in vitro , ex vivo and in vivo . While important progress has been made towards using this analytical technique in clinical applications, there is a limit to how much chemically specific information can be extracted from a spectrum of a biological sample, which consists of multiple overlapping peaks from a large number of species in any particular sample. In an attempt to elucidate more specific information regarding individual biochemical species, as opposed to very broad assignments by species class, we propose a bottom-up approach beginning with a detailed analysis of pure biochemical components. Here, we demonstrate a simple ratiometric approach applied to fatty acids, a subsection of the lipid class, to allow the key structural features, in particular degree of saturation and chain length, to be predicted. This is proposed as a starting point for allowing more chemically and species-specific information to be elucidated from the highly multiplexed spectrum of multiple overlapping signals found in a real biological sample. The power of simple ratiometric analysis is also demonstrated by comparing the prediction of degree of unsaturation in food oil samples using ratiometric and multivariate analysis techniques which could be used for food oil authentication.

scholarly journals Allelic variation in 5-HTTLPR and the effects of citalopram on the emotional neural network

2015 ◽  
Vol 206 (5) ◽  
pp. 385-392 ◽  
Author(s):  
Yina Ma ◽  
Bingfeng Li ◽  
Chenbo Wang ◽  
Wenxia Zhang ◽  
Yi Rao ◽  
...  
Keyword(s):  
Serotonin Transporter ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Allelic Variation ◽  
Brain Activity ◽  
Negative Emotions ◽  
Healthy Adults ◽  
Acute Administration ◽  
Neural Responses ◽  
Acute Effects ◽  
Imaging Results

BackgroundSelective serotonin reuptake inhibitors (SSRIs), such as citalopram, which selectively block serotonin transporter (5-HTT) activity, are widely used in the treatment of depression and anxiety disorders. Numerous neuroimaging studies have examined the effects of SSRIs on emotional processes. However, there are considerable inter-individual differences in SSRI effect, and a recent meta-analysis further revealed discrepant effects of acute SSRI administration on neural responses to negative emotions in healthy adults.AimsWe examined how a variant of the serotonin-transporter polymorphism (5-HTTLPR), which affects the expression and function of 5-HTT, influenced the acute effects of an SSRI (citalopram) on emotion-related brain activity in healthy adults.MethodCombining genetic neuroimaging, pharmacological technique and a psychological paradigm of emotion recognition, we scanned the short/short (s/s) and long/long (l/l) variants of 5-HTTLPR during perception of fearful, happy and neutral facial expressions after the acute administration of an SSRI (i.e. 30mg citalopram administered orally) or placebo administration.ResultsWe found that 5-HTTLPR modulated the acute effects of citalopram on neural responses to negative emotions. Specifically, relative to placebo, citalopram increased amygdala and insula activity in l/l but not s/s homozygotes during perception of fearful faces. Similar analyses of brain activity in response to happy faces did not show any significant effects.ConclusionsOur combined pharmacogenetic and functional imaging results provide a neurogenetic mechanism for discrepant acute effects of SSRIs.

scholarly journals Neural Burst Firing and Its Roles in Mental and Neurological Disorders

2021 ◽  
Vol 15 ◽  
Author(s):  
Jie Shao ◽  
Yunhui Liu ◽  
Dashuang Gao ◽  
Jie Tu ◽  
Fan Yang
Keyword(s):  
Neurological Disorders ◽  
High Frequency ◽  
Burst Firing ◽  
Specific Information ◽  
Neural Firing ◽  
Information Coding ◽  
Brain Areas ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channels ◽  
Ionic Mechanisms

Neural firing patterns are critical for specific information coding and transmission, and abnormal firing is implicated in a series of neural pathologies. Recent studies have indicated that enhanced burst firing mediated by T-type voltage-gated calcium channels (T-VGCCs) in specific neuronal subtypes is involved in several mental or neurological disorders such as depression and epilepsy, while suppression of T-VGCCs relieve related symptoms. Burst firing consists of groups of relatively high-frequency spikes separated by quiescence. Neurons in a variety of brain areas, including the thalamus, hypothalamus, cortex, and hippocampus, display burst firing, but the ionic mechanisms that generating burst firing and the related physiological functions vary among regions. In this review, we summarize recent findings on the mechanisms underlying burst firing in various brain areas, as well as the roles of burst firing in several mental and neurological disorders. We also discuss the ion channels and receptors that may regulate burst firing directly or indirectly, with these molecules highlighted as potential intervention targets for the treatment of mental and neurological disorders.

scholarly journals THORAX-ABDOMINAL VAGUS NERVES IN FETUSES. Nervios vagos toraco-abdominales en fetos

2016 ◽  
Vol 7 (3) ◽  
pp. 145-152
Author(s):  
Susana N Biasutto ◽  
Gabriel A F Ceccón ◽  
Matías De la Rosa ◽  
Paulina A Bortolín
Keyword(s):  
Vagus Nerve ◽  
Surgical Procedures ◽  
Carotid Arteries ◽  
Clinical Aspects ◽  
Esophageal Hiatus ◽  
Specific Information ◽  
Vagus Nerves ◽  
Clinical Procedures ◽  
Lower Neck ◽  
Upper Third

Los nervios vagos han sido exhaustivamente estudiados en los adultos pero no en los niños, y mayormente en el trayecto intracraneal, más que en la periferia. El objetivo de este estudio fue proveer información más específica sobre los nervios vagos toraco-abdominales, describirlos en fetos y asociarlos con la rotación gástrica, de modo que pueda ser aplicada a procedimientos clínicos, reduciendo la morbilidad. Se disecaron treinta fetos entre 12 y 23 semanas de gestación, mayormente varones (87%), desde la parte inferior del cuello hasta el cardias, identificando los troncos y ramas de los nervios vagos. Los nervios fueron descriptos en su ingreso en el tórax en relación con las arterias carótidas, en su posición en el tercio superior del esófago asociados con el origen de las ramas cardíacas y pulmonares, en el tercio inferior del esófago con muchas variaciones en su distribución, a nivel diafragmático en el hiato esofágico y, finalmente, en relación con la posición gástrica. La discusión involucró descripciones hechas por diferentes autores incluyendo algunos estudios recientes que proporcionan resultados electrofisio-lógicos y consideraciones de aspectos clínicos, principalmente representados por procedimientos quirúrgicos y su morbilidad, ambos asociados con la lesión de los nervios vagos. Vagus nerves have been extensively studied in adults but not in fetuses, and mostly in the intracranial pathway than the peripheral one. The objective of this study was to provide more specific information on the thorax-abdominal vagus nerves, to describe them in fetuses and to associate them with the gastric rotation, so it could be applied to clinical procedures, reducing morbidity. Thirty fetuses between 12 to 23 weeks of gestation, mainly male (87%), were dissected from the lower neck to the cardias, identifying vagus nerve trunks and braches. Vagus nerves were described at the entrance in the thorax in relation with the carotid arteries, in their position at the upper third of the esophagus associated with the origin of cardiac and pulmonary branches, in the lower third of the esophagus with many variations in their distribution, at the diaphragmatic level in the esophageal hiatus and, finally, in relation with the gastric position. The discussion involved descriptions made by different authors including some recent studies providing electrophysiological results and considerations on clinical aspects, mainly represented by surgical procedures and their morbidity associated, both to vagus nerve injury.

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