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Impact of Retinal Stimulation on Neuromodulation

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The intergeniculate leaflet (IGL) of the lateral geniculate body in the rat is a population of GABAergic neurons that can be divided into two, anatomically and neurochemically distinct populations. One population comprises neuropeptide-Y (NPY)-positive neurons that form the geniculohypothalamic tract innervating the suprachiasmatic nuclei (SCN) and the other population comprises enkephalin-positive (ENK) neurons giving rise to the geniculo-geniculate tract innervating the contralateral IGL (cIGL). Previous electrophysiological studies have observed various patterns of firing and different responses to changes in lighting conditions of IGL neurons in vitro and in vivo. The aim of the present study was to determine if these distinct properties could be ascribed to differentially projecting IGL neurons. Neuron activity was recorded extracellularly in the IGL of anaesthetised rats under different lighting conditions (i.e. light/dark). Antidromic activation was used to identify recorded cells as projecting to the SCN or the contralateral IGL. All IGL neurons identified as projecting to the contralateral IGL displayed infra-slow oscillatory activity (ISO; i.e. slow rhythmic bursts of action potentials). ISO of these neurons was sustained in the light and was diminished in the darkness. In contrast, all IGL neurons identified as projecting to the SCN displayed a low level of firing in the light and a majority of these cells increased firing in the darkness. All IGL neurons projecting to the SCN were characterised by an irregular pattern of firing in the light and dark. These data are the first to demonstrate that differentially projecting rat intergeniculate leaflet neurons are characterised by distinct firing patterns and opposite responses to light and dark conditions.
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In unilateral upper-limb complex regional pain syndrome (CRPS), the temperature of the hands is modulated by where the arms are located relative to the body midline. We hypothesized that this effect depends on the perceived location of the hands, not on their actual location, nor on their anatomical alignment. In 2 separate cross-sectional randomized experiments, 10 (6 female) unilateral CRPS patients wore prism glasses that laterally shifted the visual field by 20 degrees. Skin temperature was measured before and after 9-minute periods in which the position of one hand was changed. Placing the affected hand on the healthy side of the body midline increased its temperature (Delta degrees C = +0.47 +/- 0.14 degrees C), but not if prism glasses made the hand appear to be on the body midline (Delta degrees C = +0.07 +/- 0.06 degrees C). Similarly, when prism glasses made the affected hand appear to be on the healthy side of the body midline, even though it was not, the affected hand warmed up (Delta degrees C = +0.28 +/- 0.14 degrees C). When prism glasses made the healthy hand appear to be on the affected side of the body midline, even though it was not, the healthy hand cooled down (Delta degrees C = 0.30 +/- 0.15 degrees C). Friedman's analysis of variance and Wilcoxon pairs tests upheld the results (P < 0.01 for all). We conclude that, in CRPS, cortical mechanisms responsible for encoding the perceived location of the limbs in space modulate the temperature of the hands.
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Defective visual information processing from both central and peripheral pathways is one of the suggested mechanisms of visual hallucination in Parkinson's disease (PD). To investigate the role of retinal thinning for visual hallucination in PD, we conducted a case-control study using spectral domain optical coherence tomography. We examined a representative sample of 61 patients with PD and 30 healthy controls who had no history of ophthalmic diseases. General ophthalmologic examinations and optical coherence tomography scans were performed in each participant. Total macular thickness and the thickness of each retinal layer on horizontal scans through the fovea were compared between the groups. In a comparison between patients with PD and healthy controls, there was significant parafoveal inner nuclear layer thinning, whereas other retinal layers, including the retinal nerve fiber layer, as well as total macular thicknesses were not different. In terms of visual hallucinations among the PD subgroups, only retinal nerve fiber layer thickness differed significantly, whereas total macular thickness and the thickness of other retinal layers did not differ. The retinal nerve fiber layer was thinnest in the group that had hallucinations without dementia, followed by the group that had hallucinations with dementia, and the group that had no hallucinations and no dementia. General ophthalmologic examinations did not reveal any significant correlation with hallucinations. There were no significant correlations between retinal thicknesses and duration or severity of PD and medication dosages. The results indicate that retinal nerve fiber layer thinning may be related to visual hallucination in nondemented patients with PD. Replication studies as well as further studies to elucidate the mechanism of thinning are warranted. © 2013 Movement Disorder Society.
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The iris is the most anterior portion of the uveal tract. The pupil is round opening near the center of the iris; it is displaced slightly downward and nasally with respect to the center of the cornea. The mammalian iris sphincter is considered to be innervated by cholinergic, and the dilator muscle by adrenergic excitatory nerve fibers, and both miosis and mydriasis are the result of contraction of the iris sphincter and the dilator muscles due to activation of these excitatory nerve fibers. Pharmacological and histological investigations also reveal that the sphincter muscle is innervated in part by inhibitory adrenergic nerve fibers, and that the dilator muscle is also innervated by inhibitory cholinergic nerve fibers. In addition to the release of acetylcholine and norepinephrine by these nerves, the peripheral nerves to the mammalian iris contain various neuropeptides, although the functional role of these pepetides is not clear. It has been known for more than 100 years that two types of photosensitive cells exist in man. However, some totally blind individuals maintain a normal circadian rhythm. Such a phenomenon cannot be explained by the rod and cone functions. Recently, a new photosensitive pigment, melanopsin, was found in the dermal melanophore cells of the frog. In 2002, melanopsin-containing retinal ganglion cells (mRGCs) were discovered and revealed that mRGCs would depolarize without input from the photoreceptors, meaning that these cells are photosensitive. In the human retina, mRGCs comprise only 0.2% of all ganglion cells. Electrophysiological studies show that light slowly depolarizes mRGCs but rapidly hyperpolarizes rods and cones. The mRGCs innervate the suprachiasmatic nucleus, which is the master circadian pacemaker in mammals, and the olivary pretectal nucleus of the midbrain. In addition to their role in circadian entrainment, the mRGCs mediate the pupillary light reflex. We investigated the mechanism of photoreception by retinal photoreceptor cells, and to evaluate the relative contribution of pupil light response using the control, instigated pharmacological blockade of neurotransmission (PB) model and a transgenic model of retinal degeneration (Tg) rabbit. Although rod and cone photoreceptors disappeared in the PB and Tg models, miosis was still induced during exposure to blue light (470 nm). The greater sustained constriction of pupils to blue light in eyes with outer retinal damage reflects mRGC activation. Our study also indicated that some histologically-identified RGCs were consistent with the characteristics and structures of mRGC. Clinically, in age-related macular degeneration patients, there was no reliable recordable pupil response to red light, even at the brightest intensity but a blue light evoked a sustained pupil constriction. However, in glaucoma patients, there was no reliable recordable pupil response to the brightest intensity of blue light. These preliminary recordings in human subjects demonstrate that changes in the pupil responses to chromatic stimuli are readily detectable and easily quantifiable with standard instruments of clinical testing. We hypothesize that changes in the transient pupil response to red light and low intensity blue light may be more sensitive to cone and rod disease, whereas changes in the sustained pupil response to bright blue light may be more sensitive to optic nerve disease. Ongoing studies of the pupil are aimed at optimizing stimulus conditions that elicit pupil responses that can better localize the site of damage to rods, cones, and RGCs, to quantify the extent of disease.
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The suppression of melatonin by bright light is probably mediated by the suprachiasmatic nucleus (SCN) in humans. In animals, SCN cells have broad visual receptive fields, suggesting that peripheral bright light could be effective for melatonin suppression. Twelve healthy subjects were subjected to 1000 lux illumination for 2 hr from 0100 to 0300 on two occasions: once lighting the central visual field 5° from the center of gaze and once lighting the peripheral visual field 60° lateral to the direction of gaze. Six subjects were observed on a third occasion in dim light. The three conditions differed significantly, with less melatonin secreted in 1000 lux, but melatonin levels with central and peripheral illumination did not differ. This suggests that phototherapy using bright light in the visual periphery may be effective.
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We examined the properties of the foveal, parafoveal, and near peripheral cone lattice in human neonates. To estimate the ability of these lattices to transmit the information used in contrast sensitivity and visual acuity tasks, we constructed ideal-observer models with the optics and photoreceptors of the neonatal eye at retinal eccentricities of 0, 5, and 10°. For ideal-observer models limited by photon noise, the eye's optics, and cone properties, contrast sensitivity was higher in the parafovea and near periphery than in the fovea. However, receptor pooling probably occurs in the neonate's parafovea and near periphery as it does in mature eyes. When we add a receptor-pooling stage to the models of the parafovea and near periphery, ideal acuity is similar in the fovea, parafovea, and near periphery. Comparisons of ideal and real sensitivity indicate that optical and receptoral immaturities impose a significant constraint on neonatal contrast sensitivity and acuity, but that immaturities in later processing stages must also limit visual performance.