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Specific effects of the benzodiazepine midazolam on visual receptive fields in light and dark adapted human subjects.

Psychophysical experiments in humans have revealed similar characteristics of visual receptive fields as were found in cats and monkeys from retinal ganglion cell recordings. In addition, in some retinal ganglion cells of cats the GABA antagonist bicuculline decreases the activity of the inhibitory surround. These findings led to two predicitions: 1) benzodiazepines will selectively increase the inhibitory surround of human visual receptive fields, 2) after dark adaptation, no free GABA will be available in the synapses and benzodiazepines will have no effect on the visual system. Characteristics of human receptive fields were determined by subthreshold summation: the contrast threshold of a vertical line was measured dependent on the distance of two parallel flanking lines whose contrast was below threshold. Both hypotheses were confirmed: the threshold in the inhibitory region of receptive fields was specifically increased in a dose-dependent manner by midazolam PO (7.5 mg: P < 0.05; 15 mg: P < 0.01). In dark-adapted subjects no effect of midazolam was found. Control experiments with atropine (1 mg IV), sulpiride (100 mg IM), and levodopa (100 mg PO) showed no specific effect. The visual system may be a model to bridge the gap between animal and human psychopharmacology.

Adaptation, Ocular↗

Adaptation-dependent plasticity of rod bipolar cell axon terminal morphology in the rat retina.

We chose synaptic terminals of rat rod bipolar cells as a model system to study activity-related changes in the overall morphology and the fine structure of synaptic sites. Using confocal laser scanning microscopy in conjunction with three-dimensional reconstruction and electron microscopy, we examined the effect of light and dark adaptation on axon terminals identified by protein kinase C (PKC) immunoreactivity. Rod bipolar cell axon terminals consisted of 2-3 polymorphic boutons situated close to the ganglion cell layer and a single ovoid swelling located more distally. Both components of the terminal complex showed adaptation-dependent differences in the distribution of PKC immunoreactivity and in their morphology. In light-adapted rod bipolar cell axon terminals, PKC immunoreactivity was homogeneously distributed throughout the cytoplasm, whereas terminals from dark-adapted animals showed PKC immunoreactivity preferentially localised in the submembrane compartment and a reduced staining of the more central cytoplasm. In three-dimensional reconstructions of optical sections and at the ultrastructural level, the shape of light-adapted axon terminals was round and smooth and exhibited more convexly curved synaptic membranes. In contrast, dark-adapted terminals had irregular contours, numerous dimples and a concave synaptic curvature. No spinules of bipolar cell terminals were observed in dark-adapted material. These observations are discussed in the context of activity-related morphological plasticity of central nervous system synapses and of the functions of PKC in the cycle of vesicle fusion and retrieval at the tonically active ribbon synapses of the rod bipolar axon terminal.

Adaptation, Ocular↗

Effects of light and darkness on pH outside rod photoreceptors in the cat retina.

We recorded pH in the extracellular space surrounding rod photoreceptors in the dark-adapted eye of the cat and during illumination with double-barreled H(+)-selective microelectrodes. A pH of 7.17 was recorded in the vitreous at the retinal surface of the dark-adapted eye and this became more alkaline during light adaptation. In dark adaptation, a pH close to 7.00 was recorded in a region of maximal acidity in the extracellular space surrounding rods in the outer nuclear layer (ONL). pH steeply alkalinized as the microelectrode was moved more distally towards the retinal pigment epithelium (RPE), and almost reached the pH of the arterial blood at the apical surface of the RPE. Illumination produced an intraretinal alkalinization that was largest (up to 0.2 pH units) in the ONL, maximal in amplitude at rod-saturating intensities, and that was sustained during steady background illumination. The light-evoked alkalinization was relatively slow in onset, having a time constant (1/e) of 64 sec, and took 8-12.5 min to return to the dark-adapted level after the offset of maintained illumination. These results show that acid production by cat rods is highest in the dark, reflecting a high rate of energy metabolism, and suggest that glycolysis is required to support the dark current. Illumination, by suppressing both glycolysis and respiration, alkalinizes the extracellular space surrounding rods. The substantial change in pH outside rods from dark to light could alter pH dependent properties of the interphotoreceptor matrix.

Adaptation, Ocular↗