Dataset Information

Near field non-invasive electrophysiology of retrotrapezoid nucleus using amperometric cation sensor.

ABSTRACT: Central chemoreception is the process whereby the brainstem senses blood gas levels and adjusts homeostatic functions such as breathing and cardiovascular tone accordingly. Rodent evidence suggests that the retrotrapezoid nucleus (RTN) is a master regulator of central chemoreception, in particular, through direct sensation of acidosis induced by CO2 levels. The oscillatory dynamics caused by pH changes as sensed by the RTN surface and its relationship to the fluctuations in cation flux is not clearly understood due to the current limitations of electrophysiology tools and this article presents our investigations to address this need. A cation selective sensor fabricated from polypyrrole doped with dodecyl benzenesulfonate (PPy (DBS)) is placed over RTN in an ex-vivo en bloc brain and changes in cation concentration in the diffusion limited region above the RTN is measured due to changes in externally imposed basal pH. The novelty of this technique lies in its feasibility to detect cation fluxes from the cells in the RTN region without having to access either sides of the cell membrane. Owing to the placement of the sensor in close proximity to the tissue, we refer to this technique as near-field electrophysiology. It is observed that lowering the pH in the physiological range (7.4-7.2) results in a significant increase in cation concentration in the vicinity of RTN with a median value of ~5 ?M. The utilization of such quantifiable measurement techniques to detect sub-threshold brain activity may help provide a platform for future neural network architectures. Findings from this paper present a quantifiable, sensitive, and robust electrophysiology technique with minimal damage to the underlying tissue.

SUBMITTER: Gupta S

PROVIDER: S-EPMC7153495 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Near field non-invasive electrophysiology of retrotrapezoid nucleus using amperometric cation sensor.

Gupta Sujasha S Otero José Javier JJ Sundaresan Vishnu Baba VB Czeisler Catherine Miriam CM

Biosensors & bioelectronics 20191218

Central chemoreception is the process whereby the brainstem senses blood gas levels and adjusts homeostatic functions such as breathing and cardiovascular tone accordingly. Rodent evidence suggests that the retrotrapezoid nucleus (RTN) is a master regulator of central chemoreception, in particular, through direct sensation of acidosis induced by CO<sub>2</sub> levels. The oscillatory dynamics caused by pH changes as sensed by the RTN surface and its relationship to the fluctuations in cation flu ...[more]

PMID: 31999582

Similar Datasets

Project description:The retrotrapezoid nucleus (RTN) consists, by definition, of Phox2b-expressing, glutamatergic, non-catecholaminergic, noncholinergic neurons located in the parafacial region of the medulla oblongata. An unknown proportion of RTN neurons are central respiratory chemoreceptors and there is mounting evidence for biochemical diversity among these cells. Here, we used multiplexed in situ hybridization and single-cell RNA-Seq in male and female mice to provide a more comprehensive view of the phenotypic diversity of RTN neurons. We now demonstrate that the RTN of mice can be identified with a single and specific marker, Neuromedin B mRNA (Nmb). Most (?75%) RTN neurons express low-to-moderate levels of Nmb and display chemoreceptor properties. Namely they are activated by hypercapnia, but not by hypoxia, and express proton sensors, TASK-2 and Gpr4. These Nmb-low RTN neurons also express varying levels of transcripts for Gal, Penk, and Adcyap1, and receptors for substance P, orexin, serotonin, and ATP. A subset of RTN neurons (?20-25%), typically larger than average, express very high levels of Nmb mRNA. These Nmb-high RTN neurons do not express Fos after hypercapnia and have low-to-undetectable levels of Kcnk5 or Gpr4 transcripts; they also express Adcyap1, but are essentially devoid of Penk and Gal transcripts. In male rats, Nmb is also a marker of the RTN but, unlike in mice, this gene is expressed by other types of nearby neurons located within the ventromedial medulla. In sum, Nmb is a selective marker of the RTN in rodents; Nmb-low neurons, the vast majority, are central respiratory chemoreceptors, whereas Nmb-high neurons likely have other functions.SIGNIFICANCE STATEMENT Central respiratory chemoreceptors regulate arterial PCO2 by adjusting lung ventilation. Such cells have recently been identified within the retrotrapezoid nucleus (RTN), a brainstem nucleus defined by genetic lineage and a cumbersome combination of markers. Using single-cell RNA-Seq and multiplexed in situ hybridization, we show here that a single marker, Neuromedin B mRNA (Nmb), identifies RTN neurons in rodents. We also suggest that >75% of these Nmb neurons are chemoreceptors because they are strongly activated by hypercapnia and express high levels of proton sensors (Kcnk5 and Gpr4). The other RTN neurons express very high levels of Nmb, but low levels of Kcnk5/Gpr4/pre-pro-galanin/pre-pro-enkephalin, and do not respond to hypercapnia. Their function is unknown.

Project description:BackgroundA vectorcardiography approach to electrocardiology contributes to the non-invasive assessment of electrical heterogeneity in the ventricles of the heart and to risk stratification for cardiac events including sudden cardiac death. The aim of this study was to develop an automatic method that identifies a representative QRST complex (QRSonset to Tend) from a Frank vectorcardiogram (VCG). This method should provide reliable measurements of morphological VCG parameters and signal when such measurements required manual scrutiny.MethodsFrank VCG was recorded in a population-based sample of 1094 participants (550 women) 50-65 years old as part of the Swedish CArdioPulmonary bioImage Study (SCAPIS) pilot. Standardized supine rest allowing heart rate stabilization and adaptation of ventricular repolarization preceded a recording period lasting ≥5 minutes. In the Frank VCG a recording segment during steady-state conditions and with good signal quality was selected based on QRST variability. In this segment a representative signal-averaged QRST complex from cardiac cycles during 10s was selected. Twenty-eight morphological parameters were calculated including both conventional conduction intervals and VCG-derived parameters. The reliability and reproducibility of these parameters were evaluated when using completely automatic and automatic but manually edited annotation points.ResultsIn 1080 participants (98.7%) our automatic method reliably selected a representative QRST complex where its instability measure effectively identified signal variability due to both external disturbances ("noise") and physiologic and pathophysiologic variability, such as e.g. sinus arrhythmia and atrial fibrillation. There were significant sex-related differences in 24 of 28 VCG parameters. Some VCG parameters were insensitive to the instability value, while others were moderately sensitive.ConclusionWe developed an automatic process for identification of a signal-averaged QRST complex suitable for morphologic measurements which worked reliably in 99% of participants. This process is applicable for all non-invasive analyses of cardiac electrophysiology including risk stratification for cardiac death based on such measurements.

Dataset Information

Near field non-invasive electrophysiology of retrotrapezoid nucleus using amperometric cation sensor.

Publications

Near field non-invasive electrophysiology of retrotrapezoid nucleus using amperometric cation sensor.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets