scholarly journals Mapping axon conduction delays in vivo from microstructural MRI

2018 ◽  
Author(s):  
Mark Drakesmith ◽  
Derek K Jones
Keyword(s):  
Conduction Velocity ◽  
Action Potentials ◽  
Volume Fraction ◽  
Relative Sensitivity ◽  
Significant Advance ◽  
Relaxation Processes ◽  
Neural Communication ◽  
Axonal Density ◽  
G Ratio

AbstractThe conduction velocity (CV) of action potentials along axons is a key neurophysiological property central to neural communication. The ability to estimate CV in humans in vivo from non-invasive MRI methods would therefore represent a significant advance in neuroscience. However, there are 2 major challenges that this paper aims to address: (1) much of the complexity of the neurophysiology of action potentials cannot be captured with currently available MRI techniques. Therefore, we seek to establish the variability in CV that can be captured when predicting CV purely from parameters that can be estimated from MRI (axon diameter and g-ratio); and (2) errors inherent in existing MRI-based biophysical models of tissue will propagate through to estimates of CV, the extent to which is currently unknown.Issue (1) is investigated by performing a sensitivity analysis on a comprehensive model of axon electrophysiology and determining the relative sensitivity to various morphological and electrical parameters.The investigations suggest that 89.2 % of the variance in CV is accounted for by variation in AD and g-ratio. The observed dependency of CV on AD and g-ratio is well characterised by a previously reported model by Rushton.Issue (2) is investigated through simulation of diffusion and relaxometry MRI data for a range of axon morphologies, applying models of restricted diffusion and relaxation processes to derive estimates of axon volume fraction (AVF), AD and g-ratio and estimating CV from the derived parameters. The results show that errors in the AVF have the biggest detrimental impact on estimates of CV, particularly for sparse fibre populations (AVF< 0.3). CV estimates are most accurate (below 5% error) where AVF is above 0.3, g-ratio is between 0.6 and 0.85 and AD is below 10 µm. Fortunately, these parameter bounds are typically satisfied by most myelinated axons.In conclusion, we demonstrate that accurate CV estimates can be inferred in axon populations across a range of configurations, except in some exceptional cases or where axonal density is low. As a proof of concept, for the first time, we generated an in vivo map of conduction velocity in the human corpus callosum with estimates consistent with values previously reported from invasive electrophysiology in primates.

Modulatory effects of oligodendrocytes on the conduction velocity of action potentials along axons in the alveus of the rat hippocampal CA1 region

2007 ◽  
Vol 3 (4) ◽  
pp. 325-334 ◽  
Author(s):  
Yoshihiko Yamazaki ◽  
Yasukazu Hozumi ◽  
Kenya Kaneko ◽  
Toshimichi Sugihara ◽  
Satoshi Fujii ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Nmda Receptors ◽  
Conduction Velocity ◽  
Action Potentials ◽  
Pyramidal Neurons ◽  
Ca1 Region ◽  
Hippocampal Ca1 Region ◽  
Hippocampal Ca1 ◽  
Inward Currents

AbstractLike neurons and astrocytes, oligodendrocytes have a variety of neurotransmitter receptors and ion channels. However, except for facilitating the rapid conduction of action potentials by forming myelin and buffering extracellular K+, little is known about the direct involvement of oligodendrocytes in neuronal activities. To investigate their physiological roles, we focused on oligodendrocytes in the alveus of the rat hippocampal CA1 region. These cells were found to respond to exogenously applied glutamate by depolarization through N-methyl-D-aspartate (NMDA) receptors and non-NMDA receptors. Electrical stimulation of the border between the alveus and stratum oriens evoked inward currents through several routes involving glutamate receptors and inward rectifier K+ channels. Moreover, electrical stimulation resembling in vivo activity evoked long-lasting depolarization. To examine the modulatory effects of oligodendrocytes on neuronal activities, we performed dual, whole-cell recording on CA1 pyramidal neurons and oligodendrocytes. Direct depolarization of oligodendrocytes shortened the latencies of action potentials evoked by antidromic stimulation. These results indicate that oligodendrocytes increase the conduction velocity of action potentials by a mechanism additional to saltatory conduction, and that they have active roles in information processing in the brain.

scholarly journals In vivo Restricted-Diffusion Imaging (RDI) is sensitive to differences in axonal density in typical children and adults

2020 ◽  
Author(s):  
Dea Garic ◽  
Fang-Cheng Yeh ◽  
Paulo Graziano ◽  
Anthony Steven Dick
Keyword(s):  
Volume Fraction ◽  
Diffusion Tensor ◽  
Diffusion Imaging ◽  
Longitudinal Axis ◽  
Restricted Diffusion ◽  
Adults And Children ◽  
Axonal Density ◽  
Shell Acquisition ◽  
Do So

ABSTRACTBackgroundThe ability to dissociate axonal density in vivo from other microstructural properties of white matter is important for the diagnosis and treatment of neurologic disease, and new methods to do so are being developed. We investigated one such method–restricted diffusion imaging (RDI)–to see whether it can more accurately replicate histological axonal density patterns in the corpus callosum (CC) of adults and children compared to diffusion tensor imaging (DTI), neurite orientation dispersion and density imaging (NODDI), and generalized q-sampling imaging (GQI) methods. To do so, we compared known axonal density patterns defined by histology to to diffusion-weighted imaging (DWI) scans of 840 healthy 20- to 40-year-old adults, and, in a replication and extension, to DWI scans of 129 typically developing 7-month-old to 18-year-old children and adolescents. Contrast analyses were used to to compare pattern similarities between the in-vivo metric and previously-published histological density models. We found that RDI was effective at mapping axonal density of small (Cohen’s d= 2.60) and large fiber sizes (Cohen’s d= 2.84) in adults. The same pattern was observed in the developing sample (Cohen’s d= 3.09 and 3.78, respectively). Other metrics, notably NODDI’s intracellular volume fraction (ICVF), were also sensitive to differences in axonal density across the longitudinal axis of the CC. In conclusion, the study showed that RDI is effective at measuring axonal density of small and large axons in adults and children, with both single- and multi-shell acquisition DWI data. Its effectiveness and availability to be used on standard as well as advanced DWI acquisitions makes it a promising method in clinical settings.

scholarly journals A predictive in vitro risk assessment platform for pro-arrhythmic toxicity using human 3D cardiac microtissues

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Celinda M. Kofron ◽  
Tae Yun Kim ◽  
Fabiola Munarin ◽  
Arvin H. Soepriatna ◽  
Rajeev J. Kant ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Action Potentials ◽  
Induced Pluripotent Stem Cell ◽  
Human Action ◽  
Environmental Toxicants ◽  
Pharmaceutical Drugs ◽  
Industrial Chemicals ◽  
Endocrine Disrupting Chemical

AbstractCardiotoxicity of pharmaceutical drugs, industrial chemicals, and environmental toxicants can be severe, even life threatening, which necessitates a thorough evaluation of the human response to chemical compounds. Predicting risks for arrhythmia and sudden cardiac death accurately is critical for defining safety profiles. Currently available approaches have limitations including a focus on single select ion channels, the use of non-human species in vitro and in vivo, and limited direct physiological translation. We have advanced the robustness and reproducibility of in vitro platforms for assessing pro-arrhythmic cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes and human cardiac fibroblasts in 3-dimensional microtissues. Using automated algorithms and statistical analyses of eight comprehensive evaluation metrics of cardiac action potentials, we demonstrate that tissue-engineered human cardiac microtissues respond appropriately to physiological stimuli and effectively differentiate between high-risk and low-risk compounds exhibiting blockade of the hERG channel (E4031 and ranolazine, respectively). Further, we show that the environmental endocrine disrupting chemical bisphenol-A (BPA) causes acute and sensitive disruption of human action potentials in the nanomolar range. Thus, this novel human 3D in vitro pro-arrhythmic risk assessment platform addresses critical needs in cardiotoxicity testing for both environmental and pharmaceutical compounds and can be leveraged to establish safe human exposure levels.

N-cholinergic facilitation of glutamate release from an individual retinotectal fiber in frog

2001 ◽  
Vol 18 (4) ◽  
pp. 549-558 ◽  
Author(s):  
A. KURAS ◽  
N. GUTMANIENĖ
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Action Potentials ◽  
Acetylcholine Receptors ◽  
Kynurenic Acid ◽  
Glutamate Release ◽  
Synaptic Potentials ◽  
Lower Vertebrates ◽  
Optic Fibers ◽  
Retinotectal Transmission

Nicotinic acetylcholine receptors are localized on retinotectal axons' terminals in lower vertebrates. The effects of activation of these receptors by endogenous acetylcholine were observed under stimulation of mass optic fibers. This study was designed to determine whether endogenous acetylcholine facilitates frog retinotectal transmission, provided only the synapses of an individual optic axon are activated, and to evaluate the feasible extent of nicotinic facilitation in these synapses by applied agonist. To this end, the effects of cholinergic drugs on the extracellular action and synaptic potentials recorded from the terminal arborization of a separate retinotectal fiber (in layer F of the tectum) were investigated in vivo. Glutamatergic nature of retinotectal synapses was reexamined by treatment with kynurenic acid. Both kynurenic acid (0.25–1 mM) and d-tubocurarine chloride (10–15 μM) significantly depressed the synaptic potentials. Carbamylcholine chloride (50–150 μM) evoked a large augmentation of the synaptic potentials and a slight but statistically significant decrease of the action potentials. D-tubocurarine reduced the effect of carbamylcholine. Pilocarpine hydrochloride (50 μM) had only a weak effect. The paired-pulse facilitation of the synaptic potentials changed significantly under the action of carbamylcholine and d-tubocurarine. The obtained results suggest that the glutamate release from activated synapses of individual retinotectal axons is facilitated by endogenous acetylcholine via presynaptic nicotinic receptors. Under used stimulation conditions, this modulation mechanism was employed only partially since its activation by applied carbamylcholine could enhance synaptic transmission up to 2.8 times.

Electronmicroscopic and electrophysiological studies of the teat branch of the XIII thoracic nerve: relationship with lactation in the rat

1988 ◽  
Vol 118 (3) ◽  
pp. 471-483 ◽  
Author(s):  
L. M. Voloschin ◽  
E. Décima ◽  
J. H. Tramezzani
Keyword(s):  
Electrical Stimulation ◽  
Conduction Velocity ◽  
Action Potentials ◽  
Silent Period ◽  
High Amplitude ◽  
Milk Ejection ◽  
Nerve Activity ◽  
Thoracic Nerve ◽  
Myelinated Fibres ◽  
Stimulation Of

ABSTRACT Electrical stimulation of the XIII thoracic nerve (the 'mammary nerve') causes milk ejection and the release of prolactin and other hormones. We have analysed the route of the suckling stimulus at the level of different subgroups of fibres of the teat branch of the XIII thoracic nerve (TBTN), which innervates the nipple and surrounding skin, and assessed the micromorphology of the TBTN in relation to lactation. There were 844 ± 63 and 868 ± 141 (s.e.m.) nerve fibres in the TBTN (85% non-myelinated) in virgin and lactating rats respectively. Non-myelinated fibres were enlarged in lactating rats; the modal value being 0·3–0·4 μm2 for virgin and 0·4–0·5 μm2 for lactating rats (P > 0·001; Kolmogorov–Smirnov test). The modal value for myelinated fibres was 3–6 μm2 in both groups. The compound action potential of the TBTN in response to electrical stimulation showed two early volleys produced by the Aα- and Aδ-subgroups of myelinated fibres (conduction velocity rate of 60 and 14 m/s respectively), and a late third volley originated in non-myelinated fibres ('C') group; conduction velocity rate 1·4 m/s). Before milk ejection the suckling pups caused 'double bursts' of fibre activity in the Aδ fibres of the TBTN. Each 'double burst' consisted of low amplitude action potentials and comprised two multiple discharges (33–37 ms each) separated by a silent period of around 35 ms. The 'double bursts' occurred at a frequency of 3–4/s, were triggered by the stimulation of the nipple and were related to fast cheek movements visible only by watching the pups closely. In contrast, the Aα fibres of the TBTN showed brief bursts of high amplitude potentials before milk ejection. These were triggered by the stimulation of cutaneous receptors during gross slow sucking motions of the pup (jaw movements). Immediately before the triggering of milk ejection the mother was always asleep and a low nerve activity was recorded in the TBTN at this time. When reflex milk ejection occurred, the mother woke and a brisk increase in nerve activity was detected; this decreased when milk ejection was accomplished. In conscious rats the double-burst type of discharges in Aδ fibres was not observed, possibly because this activity cannot be detected by the recording methods currently employed in conscious animals. During milk ejection, action potentials of high amplitude were conveyed in the Aα fibres of the TBTN. During the treading time of the stretch reaction (SR), a brisk increase in activity occurred in larger fibres; during the stretching periods of the SR a burst-type discharge was again observed in slow-conducting afferents; when the pups changed nipple an abrupt increase in activity occurred in larger fibres. In summary, the non-myelinated fibres of the TBTN are increased in diameter during lactation, and the pattern of suckling-evoked nerve activity in myelinated fibres showed that (a) the double burst of Aδ fibres, produced by individual sucks before milk ejection, could be one of the conditions required for the triggering of the reflex, and (b) the nerve activity displayed during milk-ejection action may result, at least in part, from 'non-specific' stimulation of cutaneous receptors. J. Endocr. (1988) 118, 471–483

Severe myocardial dysfunction induced by ventricular remodeling in aging rat hearts

1990 ◽  
Vol 259 (4) ◽  
pp. H1086-H1096 ◽  
Author(s):  
J. M. Capasso ◽  
T. Palackal ◽  
G. Olivetti ◽  
P. Anversa
Keyword(s):  
Ventricular Remodeling ◽  
Volume Fraction ◽  
Diastolic Pressure ◽  
Structural Characteristics ◽  
Myocardial Dysfunction ◽  
Pressure Rise ◽  
Wall Stress ◽  
Left Ventricular ◽  
Cross Sectional

To determine if aging engenders alterations in the functional properties of the myocardium and ventricular remodeling, the hemodynamic performance and structural characteristics of the left ventricle of male Fischer 344 rats at 4, 12, 20, and 29 mo of age were studied by quantitative physiology and morphology. In vivo assessment of cardiac pump function showed no change up to 20 mo, whereas left ventricular end-diastolic pressure was increased at 29 mo. Moreover, peak rates of pressure rise and decay, stroke volume, ejection fraction, and cardiac output were depressed at the later age interval, demonstrating the presence of ventricular failure at this time. The measurements of chamber size and wall thickness showed that ventricular end-diastolic and end-systolic volumes progressively increased with age with the greatest change occurring at 20-29 mo. Aging was also accompanied by a marked augmentation in the volume fraction of fibrotic areas in the ventricular myocardium that was due to an increase in their number and cross-sectional area with time. These architectural rearrangements, in combination with the abnormalities in ventricular function, resulted in an elevation in the volume of wall stress throughout the cardiac cycle. Wall stress increased by 64, 44, and 50% from 4 to 12, 12 to 20, and 20 to 29 mo of age. In conclusion, aging leads to a continuous rise in wall stress that is not normalized by ventricular remodeling. These two independent processes appear to be responsible for the onset of heart failure in the senescent rat.

scholarly journals Conduction velocity of the rabbit facial nerve: a noninvasive functional evaluation

2003 ◽  
Vol 17 (2) ◽  
pp. 126-131 ◽  
Author(s):  
Belmiro Cavalcanti do Egito Vasconcelos ◽  
Cosme Gay Escoda ◽  
Ricardo José de Holanda Vasconcellos ◽  
Riedel Frota Sá Nogueira Neves
Keyword(s):  
Facial Nerve ◽  
Conduction Velocity ◽  
Nerve Conduction ◽  
Action Potentials ◽  
Functional Evaluation ◽  
Surface Electrodes ◽  
Nerve Grafts ◽  
Synthetic Materials ◽  
Facial Nerves ◽  
The Mean

The aim of this study was to evaluate standardized conduction velocity data for uninjured facial nerve and facial nerve repaired with autologous graft nerves and synthetic materials. An evaluation was made measuring the preoperative differences in the facial nerve conduction velocities on either side, and ascertaining the existence of a positive correlation between facial nerve conduction velocity and the number of axons regenerated postoperatively. In 17 rabbits, bilateral facial nerve motor action potentials were recorded pre- and postoperatively. The stimulation surface electrodes were placed on the auricular pavilion (facial nerve trunk) and the recording surface electrodes were placed on the quadratus labii inferior muscle. The facial nerves were isolated, transected and separated 10 mm apart. The gap between the two nerve ends was repaired with autologous nerve grafts and PTFE-e (polytetrafluoroethylene) or collagen tubes. The mean of maximal conduction velocity of the facial nerve was 41.10 m/s. After 15 days no nerve conduction was evoked in the evaluated group. For the period of 2 and 4 months the mean conduction velocity was approximately 50% of the normal value in the subgroups assessed. A significant correlation was observed between the conduction velocity and the number of regenerated axons. Noninvasive functional evaluation with surface electrodes can be useful for stimulating and recording muscle action potentials and for assessing the functional state of the facial nerve.

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