scholarly journals Dopamine-Mediated Volume Transmission in Midbrain Is Regulated by Distinct Extracellular Geometry and Uptake

2001 ◽  
Vol 85 (4) ◽  
pp. 1761-1771 ◽  
Author(s):  
Stephanie J. Cragg ◽  
Charles Nicholson ◽  
June Kume-Kick ◽  
Lian Tao ◽  
Margaret E. Rice
Keyword(s):  
Point Source ◽  
Time Course ◽  
Volume Fraction ◽  
Extracellular Volume ◽  
Brain Slices ◽  
Extracellular Volume Fraction ◽  
Receptor Activation ◽  
Substantia Nigra Pars Compacta ◽  
Volume Transmission ◽  
Carbon Fiber Microelectrodes

Somatodendritic release of dopamine (DA) in midbrain is, at least in part, nonsynaptic; moreover, midbrain DA receptors are predominantly extrasynaptic. Thus somatodendritic DA mediates volume transmission, with an efficacy regulated by the diffusion and uptake characteristics of the local extracellular microenvironment. Here, we quantitatively evaluated diffusion and uptake in substantia nigra pars compacta (SNc) and reticulata (SNr), ventral tegmental area (VTA), and cerebral cortex in guinea pig brain slices. The geometric parameters that govern diffusion, extracellular volume fraction (α) and tortuosity (λ), together with linear uptake ( k′), were determined for tetramethylammonium (TMA+), and for DA, using point-source diffusion combined with ion-selective and carbon-fiber microelectrodes. TMA+-diffusion measurements revealed a large α of 30% in SNc, SNr, and VTA, which was significantly higher than the 22% in cortex. Values for λ and k′ for TMA+ were similar among regions. Point-source DA-diffusion curves fitted theory well with linear uptake, with significantly higher values of k′ for DA in SNc and VTA (0.08–0.09 s− 1) than in SNr (0.006 s− 1), where DA processes are sparser. Inhibition of DA uptake by GBR-12909 caused a greater decrease in k′ in SNc than in VTA. In addition, DA uptake was slightly decreased by the norepinephrine transport inhibitor, desipramine in both regions, although this was statistically significant only in VTA. We used these data to model the radius of influence of DA in midbrain. Simulated release from a 20-vesicle point source produced DA concentrations sufficient for receptor activation up to 20 μm away with a DA half-life at this distance of several hundred milliseconds. Most importantly, this model showed that diffusion rather than uptake was the most important determinant of DA time course in midbrain, which contrasts strikingly with the striatum where uptake dominates. The issues considered here, while specific for DA in midbrain, illustrate fundamental biophysical properties relevant for all extracellular communication.

Anisotropic and heterogeneous diffusion in the turtle cerebellum: implications for volume transmission

1993 ◽  
Vol 70 (5) ◽  
pp. 2035-2044 ◽  
Author(s):  
M. E. Rice ◽  
Y. C. Okada ◽  
C. Nicholson
Keyword(s):  
Time Course ◽  
Granular Layer ◽  
Volume Fraction ◽  
Molecular Layer ◽  
Extracellular Volume ◽  
Striking Difference ◽  
Volume Transmission ◽  
Anisotropic Porous Media ◽  
Parallel Fibers ◽  
Ion Shifts

1. Measurements of extracellular diffusion properties were made in three orthogonal axes of the molecular and granular layers of the isolated turtle cerebellum with the use of iontophoresis of tetramethylammonium (TMA+) combined with ion-selective microelectrodes. 2. Diffusion in the extracellular space of the molecular layer was anisotropic, that is, there was a different value for the tortuosity factor, lambda i, associated with each axis of that layer. The x- and y-axes lay in the plane parallel to the pial surface of this lissencephalic cerebellum with the x-axis in the direction of the parallel fibers. The z-axis was perpendicular this plane. The tortuosity values were lambda x = 1.44 +/- 0.01, lambda y = 1.95 +/- 0.02, and lambda z = 1.58 +/- 0.01 (mean +/- SE). By contrast, the granular layer was isotropic with a single tortuosity value, lambda Gr = 1.77 +/- 0.01. 3. These data confirm the applicability of appropriately extended Fickian equations to describe diffusion in anisotropic porous media, including brain tissue. 4. Heterogeneity between the molecular and granular layer was revealed by a striking difference in extracellular volume fraction, alpha, for each layer. In the molecular layer alpha = 0.31 +/- 0.01, whereas in the granular layer alpha = 0.22 +/- 0.01. 5. Volume fraction and tortuosity affected the time course and amplitude of extracellular TMA+ concentration after iontophoresis. This was modeled by the use of the average parameters determined experimentally, and the nonspherical pattern of diffusion in the molecular layer was compared with the spherical distribution in the granular layer and agarose gel by computing isoconcentration ellipsoids. 6. One functional consequence of these results was demonstrated by measuring local changes in [K+]o and [Ca2+]o after microiontophoresis of a cerebellar transmitter, glutamate. The ratios of ion shifts in the x- and y-axes in the granular layer were close to unity, with a ratio of 1.04 +/- 0.08 for the rise in [K+]o and 1.03 +/- 0.17 for the decrease in [Ca2+]o. In contrast, ion shifts in the molecular layer had an x:y ratio of 1.44 +/- 0.14 for the rise in [K+]o and 2.10 +/- 0.42 for the decrease in [Ca2+]o. 7. These data demonstrate that the structure of cellular aggregates can channel the migration of substances in the extracellular microenvironment, and this could be a mechanism for volume transmission of chemical signals. For example, the preferred diffusion direction of glutamate along the parallel fibers would help constrain an incoming excitatory stimulus to stay "on-beam."

Transmural heterogeneity of diffusion anisotropy in the sheep myocardium characterized by MR diffusion tensor imaging

2007 ◽  
Vol 293 (4) ◽  
pp. H2377-H2384 ◽  
Author(s):  
Yi Jiang ◽  
Julius M. Guccione ◽  
Mark B. Ratcliffe ◽  
Edward W. Hsu
Keyword(s):  
Diffusion Tensor Imaging ◽  
Volume Fraction ◽  
Diffusion Tensor ◽  
Extracellular Volume ◽  
Extracellular Volume Fraction ◽  
Left Ventricular ◽  
Fiber Direction ◽  
Significant Difference ◽  
Mr Diffusion ◽  
Mr Diffusion Tensor Imaging

The orientation of MRI-measured diffusion tensor in the myocardium has been directly correlated to the tissue fiber direction and widely characterized. However, the scalar anisotropy indexes have mostly been assumed to be uniform throughout the myocardial wall. The present study examines the fractional anisotropy (FA) as a function of transmural depth and circumferential and longitudinal locations in the normal sheep cardiac left ventricle. Results indicate that FA remains relatively constant from the epicardium to the midwall and then decreases (25.7%) steadily toward the endocardium. The decrease of FA corresponds to 7.9% and 12.9% increases in the secondary and tertiary diffusion tensor diffusivities, respectively. The transmural location of the FA transition coincides with the location where myocardial fibers run exactly circumferentially. There is also a significant difference in the midwall-endocardium FA slope between the septum and the posterior or lateral left ventricular free wall. These findings are consistent with the cellular microstructure from histological studies of the myocardium and suggest a role for MR diffusion tensor imaging in characterization of not only fiber orientation but, also, other tissue parameters, such as the extracellular volume fraction.

Abstract 17263: Pre-Clinical Left Ventricular Myocardial Remodeling in Patients With Friedreich’s Ataxia: A Cardiac MRI Study

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_1) ◽  
Author(s):  
Karen A Takazaki1 ◽  
Thiago Quinaglia A. C. Silva ◽  
Alberto Martinez ◽  
Tomas Neilan ◽  
Ravi SHAH ◽  
...  
Keyword(s):  
Heart Failure ◽  
Volume Fraction ◽  
Extracellular Volume ◽  
Extracellular Volume Fraction ◽  
Friedreich’S Ataxia ◽  
Left Ventricular ◽  
Friedreich's Ataxia ◽  
Intracellular Water ◽  
Lv Mass ◽  
Burn Out

Background: Heart Failure (HF) is the most common cause of death in Friedreich’s ataxia (FRDA), an inherited mitochondrial disease. Myocardial fibrosis is a well-documented histopathological feature among FRDA patients with HF. Objectives: In this study we will investigate the myocardial extracellular volume fraction (ECV) and intracellular water lifetime (τ ic ), using T1-weighted CMR imaging, in a cohort of patients with FRDA without signs of heart failure. We will also investigate whether myocardial tissue phenotyping by CMR can highlight particular characteristics of LV remodeling in FRDA’s cardiomyopathy, beyond those currently assessed with imaging-based classification of disease severity. Methods: Twenty-six FRDA’s patients (age 26.6±9.3 years, 15 women) without signs of HF, and 10 healthy controls (32.6±7.3 years, 5 women) underwent cardiac magnetic resonance (CMR) studies for assessment of left ventricular (LV) function, myocardial T1, late gadolinium enhancement (LGE), extracellular volume fraction (ECV), and intracellular water-lifetime (τ ic ) as marker of cardiomyocyte size. Neurological decline was determined using the FRDA rating scale (FARS 3). Results: FRDA patients had normal LV ejection fraction (LVEF: 67.66±11.4 vs. 63.9±9.0, P=0.311), larger LV mass index (LVMASSi: 61.03±22.1 vs. 45±4.2g/m 2 , P<0.001), and decreased LV end-diastolic volume index (LVEDVi 53.42±12 vs. 75.7±16.1, P=0.002), compared with controls. ECV and τ ic , were increased in FRDA patients (ECV: 0.36±0.05 vs. 0.25±0.02, P<0.0001; τ ic : 0.13±0.07 vs. 0.06±0.03, P=0.001). ECV was positively associated with LV mass-to-volume ratio (r=0.628, P<0.001). FARS 3 correlated positively with disease duration (r=0.669, P<0.001), and negatively with τ ic , (r=0.478, P=0.039). LVMASSi and cardiomyocyte mass-index [(1–ECV)LVMASSi] declined with age, indicating that LV hypertrophy may transition to a “burn-out” phase with LV atrophy. Conclusions: LV hypertrophy in FRDA reflects an expansion of the myocardial interstitium and an increase in cardiomyocyte size. In contrast, the neurological decline was more likely with decreasing cardiomyocyte size, possibly an early sign of myocardial “burn-out” in FRDA.

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