Non-neuronal, slow GABA signalling in the ventrobasal thalamus targets δ-subunit-containing GABA(A) receptors

The rodent ventrobasal (VB) thalamus contains a relatively uniform population of thalamocortical (TC) neurons that receive glutamatergic input from the vibrissae and the somatosensory cortex, and inhibitory input from the nucleus reticularis thalami (nRT). In this study we describe ?-aminobutyric acid (GABA)(A) receptor-dependent slow outward currents (SOCs) in TC neurons that are distinct from fast inhibitory postsynaptic currents (IPSCs) and tonic currents. SOCs occurred spontaneously or could be evoked by hypo-osmotic stimulus, and were not blocked by tetrodotoxin, removal of extracellular Ca(2+) or bafilomycin A1, indicating a non-synaptic, non-vesicular GABA origin. SOCs were more common in TC neurons of the VB compared with the dorsal lateral geniculate nucleus, and were rarely observed in nRT neurons, whilst SOC frequency in the VB increased with age. Application of THIP, a selective agonist at d-subunit-containing GABA(A) receptors, occluded SOCs, whereas the benzodiazepine site inverse agonist ß-CCB had no effect, but did inhibit spontaneous and evoked IPSCs. In addition, the occurrence of SOCs was reduced in mice lacking the d-subunit, and their kinetics were also altered. The anti-epileptic drug vigabatrin increased SOC frequency in a time-dependent manner, but this effect was not due to reversal of GABA transporters. Together, these data indicate that SOCs in TC neurons arise from astrocytic GABA release, and are mediated by d-subunit-containing GABA(A) receptors. Furthermore, these findings suggest that the therapeutic action of vigabatrin may occur through the augmentation of this astrocyte-neuron interaction, and highlight the importance of glial cells in CNS (patho) physiology.

A linear chromatic mechanism drives the pupillary response

Previous studies have shown that a chromatic mechanism can drive pupil responses. The aim of this research was to clarify whether a linear or nonlinear chromatic mechanism drives pupillary responses by using test stimuli of various colours that are defined in cone contrast space. The pupil and accommodation responses evoked by these test stimuli were continuously and simultaneously objectively measured by photorefraction. The results with isochromatic and isoluminant stimuli showed that (lie accommodative level remained approximately constant (<0.25 D change in mean level) even when the concurrent pupillary response was large (ca. 0.30mm). The pupillary response to an isoluminant grating was sustained, delayed by ca. 60 ms) and larger in amplitude than that for a isochromatic uniform stimulus, which supports previous work suggesting that the chromatic mechanism contributes to the pupillary response. In a second experiment, selected chromatic test gratings were used and isoresponse contours in cone contrast space were obtained. The results showed that the isoresponse contour in cone contrast space is well described (r2 = 0.99) by a straight line with a positive slope. The results indicate that a [L-M] linear chromatic mechanism, whereby a signal from the long wavelength cone is subtracted from that of the middle wavelength cone and vice versa, drives pupillary responses.

Microstructure-based inherent anisotropy of asphalt mixtures

Asphalt mixtures have been demonstrated to be anisotropic materials in both laboratory and field tests. The anisotropy of asphalt mixtures consists of inherent anisotropy and stress-induced anisotropy. In previous work, the inherent anisotropy of asphalt mixtures was quantified by using only the inclination angles of the coarse aggregate particles in the asphalt mixtures. However, the inclination of fine aggregates also has a contribution to the inherent anisotropy. Moreover, the contribution to the inherent anisotropy of each aggregate may not be the same as in the previous work but will depend on the size, orientation, and sphericity of the aggregate particle. This paper quantifies the internal microstructure of the aggregates in asphalt mixtures by using an aggregate-related geometric parameter, the vector magnitude. The original formulation of the vector magnitude, which addresses only the orientation of coarse aggregates, is modified to account for not only the coarse aggregate orientation, but also the size, orientation, and sphericity of coarse and fine aggregates. This formulation is applied to cylindrical lab-mixed lab-compacted asphalt mixture specimens varying in asphalt binder type, air void content, and aging period. The vertical modulus and the horizontal modulus are also measured by using nondestructive tests. A relationship between the modified vector magnitude and the modulus ratio of the vertical modulus to the horizontal modulus is developed to quantify the influence of the inherent microstructure of the aggregates on the anisotropy of the mixtures. The modulus ratio is found to depend solely on the aggregate characteristics including the inclination angle, size, and sphericity, and it is independent of the asphalt binder type, air void content, and aging period. The inclination angle, itself, proves to be insufficient to quantify the inherent anisotropy of the asphalt mixtures. © 2011 American Society of Civil Engineers.