Light sensitivity in a vertebrate mechanoreceptor?

Using immunohistochemistry and western blot analysis, we demonstrate that melanopsin is localised in cells around the central pore of lateral line neuromasts in the African clawed frog, Xenopus laevis. Since melanopsin is a known photoreceptor pigment with diverse functions in vertebrates, we suggest that the lateral line of Xenopus laevis, which is primarily a mechanoreceptor, might also be light sensitive. Potential functions of such photosensitivity are discussed, including its role in mediating locomotor responses following dermal illumination.

Survival of Dopaminergic Amacrine Cells after Near-Infrared Light Treatment in MPTP-Treated Mice.

We examined whether near-infrared light (NIr) treatment (photobiomodulation) saves dopaminergic amacrine cells of the retina in an acute and a chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson disease. For the acute model, BALB/c mice had MPTP (100 mg/kg) or saline injections over 30 hours, followed by a six-day-survival period. For the chronic model, mice had MPTP (200 mg/kg) or saline injections over five weeks, followed by a three-week-survival period. NIr treatment was applied either at the same time (simultaneous series) or well after (posttreatment series) the MPTP insult. There were four groups within each series: Saline, Saline-NIr, MPTP, and MPTP-NIr. Retinae were processed for tyrosine hydroxylase (TH) immunochemistry, and cell number was analysed. In the MPTP groups, there was a significant reduction in TH(+) cell number compared to the saline controls; this reduction was greater in the acute (~50%) compared to the chronic (~30%) cases. In the MPTP-NIr groups, there were significantly more TH(+) cells than in the MPTP groups of both series (~30%). In summary, we showed that NIr treatment was able to both protect (simultaneous series) and rescue (posttreatment series) TH(+) cells of the retina from parkinsonian insult.

Patterns of Cell Activity in the Subthalamic Region Associated with the Neuroprotective Action of Near-Infrared Light Treatment in MPTP-Treated Mice.

We have shown previously that near-infrared light (NIr) treatment or photobiomodulation neuroprotects dopaminergic cells in substantia nigra pars compacta (SNc) from degeneration induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice. The present study explores whether NIr treatment changes the patterns of Fos expression in the subthalamic region, namely, the subthalamic nucleus (STN) and zona incerta (ZI); both cell groups have abnormally overactive cells in parkinsonian cases. BALB/c mice were treated with MPTP (100-250 mg/kg) or saline either over 30 hours followed by either a two-hour or six-day survival period (acute model) or over five weeks followed by a three-week survival period (chronic model). NIr and MPTP were applied simultaneously. Brains were processed for Fos immunochemistry, and cell number was estimated using stereology. Our major finding was that NIr treatment reduced (30-45%) the increase in Fos(+) cell number evident in the STN and ZI after MPTP insult. This reduction was concurrent with the neuroprotection of dopaminergic SNc cells shown previously and was evident in both MPTP models (except for the 2 hours survival period which showed no changes in cell number). In summary, our results indicated that NIr had long lasting effects on the activity of cells located deep in the brain and had repaired partially the abnormal activity generated by the parkinsonian toxin.

Photobiomodulation enhances nigral dopaminergic cell survival in a chronic MPTP mouse model of Parkinson's disease.

We have shown previously that photobiomodulation or near-infrared light (NIr) treatment protects dopaminergic cells of the substantia nigra pars compacta (SNc) in an acute MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) model of Parkinson's disease (PD). In this study, we tested the protective and rescue action of NIr treatment in a chronic MPTP model, developed to resemble more closely the slow progressive degeneration in PD patients. We examined three regions of dopaminergic cells, the SNc, periaqueductal grey matter (PaG) and zona incerta-hypothalamus (ZI-Hyp). BALB/c mice had MPTP or saline injections over five weeks, followed by a three-week survival. NIr treatment was applied either at the same time as (simultaneous series) or after (post-treatment series) the MPTP insult. There were four groups within each series; Saline, Saline-NIr, MPTP and MPTP-NIr. Brains were processed for tyrosine hydroxylase (TH) immunochemistry and cell number was analysed using the optical fractionator method. In the SNc, there was a significant reduction (≈ 45%) in TH(+) cell number in the MPTP groups compared to the saline controls of both series. In the MPTP-NIr groups of both series, TH(+) cell number was significantly higher (≈ 25%) than in the MPTP groups, but lower than in the saline controls (≈ 20%). By contrast in the PaG and ZI-Hyp, there were no significant differences in TH(+) cell number between the MPTP an MPTP-NIr groups of either series. In summary, exposure to NIr either at the same time or well after chronic MPTP insult saved many SNc dopaminergic cells from degeneration.

Neuroprotection of midbrain dopaminergic cells in MPTP-treated mice after near-infrared light treatment.

This study explores whether near-infrared (NIr) light treatment neuroprotects dopaminergic cells in the substantia nigra pars compacta (SNc) and the zona incerta-hypothalamus (ZI-Hyp) from degeneration in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. BALB/c albino mice were divided into four groups: 1) Saline, 2) Saline-NIr, 3) MPTP, 4) MPTP-NIr. The injections were intraperitoneal and they were followed immediately by NIr light treatment (or not). Two doses of MPTP, mild (50 mg/kg) and strong (100 mg/kg), were used. Mice were perfused transcardially with aldehyde fixative 6 days after their MPTP treatment. Brains were processed for tyrosine hydroxylase (TH) immunochemistry. The number of TH(+) cells was estimated using the optical fractionator method. Our major finding was that in the SNc there were significantly more dopaminergic cells in the MPTP-NIr compared to the MPTP group (35%-45%). By contrast, in the ZI-Hyp there was no significant difference in the numbers of cells in these two groups. In addition, our results indicated that survival in the two regions after MPTP insult was dose-dependent. In the stronger MPTP regime, the magnitude of loss was similar in the two regions ( approximately 60%), while in the milder regime cell loss was greater in the SNc (45%) than ZI-Hyp ( approximately 30%). In summary, our results indicate that NIr light treatment offers neuroprotection against MPTP toxicity for dopaminergic cells in the SNc, but not in the ZI-Hyp.

Abnormal axons in the albino optic tract.

PURPOSE: There have been suggestions that the misrouting of axons at the optic chiasm leading to the abnormal ratio of crossed to uncrossed axons in the optic tract of albinos is a consequence of abnormal timing of ganglion cell axon outgrowth. The sequence of genesis of ganglion cell classes and their axon outgrowth is correlated with the deep-to-superficial distribution of their axons by size in the mammalian optic tract. Optic tract axon order in albino and normally pigmented ferrets was, therefore, examined to determine whether an abnormal pattern of retinal ganglion cell genesis and axon outgrowth is evident in albinos. METHODS: Light and electron microscopy were used to study axon diameters and myelin thickness of axons in the optic tracts of adult albino and pigmented ferrets. RESULTS: In the optic tract, large-diameter axons are confined superficially in the normally pigmented ferret but are present throughout its depth in albinos. The abnormally located large axons and neighboring small-diameter axons in the albino have an abnormal axon diameter/myelin thickness ratio; large-diameter axons are poorly myelinated, and small-diameter axons exhibit an abnormally thick myelin sheath. These deep abnormal axons originate from the contralateral retina. CONCLUSIONS: In addition to the known disruptions of normal organization in the visual system, albinos have an abnormal axon diameter distribution and a population of morphologically abnormal axons in the optic tract. These abnormal axons may represent the population of aberrantly crossed axons found in all albino mammals.

Protein kinase C immunoreactivity in the pigmented and albino rat retina.

The albino retina is abnormal. The central region is under-developed and some cell populations are reduced or increased in number. Not least of these anomalies is the deficit in the rod population in hypopigmented rodents and carnivores. Given this abnormality we have examined the distribution of rod bipolar cells in albino rats to determine whether this subsequent stage in the rod pathway is similarly disrupted. A monoclonal antibody to protein kinase C was used to determine the distribution of rod bipolar cells in juvenile and adult pigmented and albino rats. Immunoreactive rod bipolar cells and their processes were counted in transverse sections passing through both the central and peripheral retina. The mean densities of immunoreactive cells were significantly reduced in albino retinas at both juvenile (postnatal day 15) and adult stages, in the former by 14% and the latter by 9%. This was evident across the entire central-to-peripheral extent of the retina. The reduced rod photoreceptor population found in albinos appears therefore to be consequential for the magnitude of their major target population, rod bipolar cells. The decrease in the rod bipolar population indicates a change in retinal cytoarchitecture and implies a disruption of functional organization of the albino retina, especially that underlying the scotopic channel. This, coupled with observations that some other retinal interneuronal populations may be disrupted, implies disordered retinal processing in albinos and emphasizes the likelihood that abnormal visual function in albinos may be as much a result of anomalous retinal circuitry as of the known photoreceptor deficit or chiasmatic misrouting.

An investigation of the role of auditory cortex in sound localization using muscimol-releasing Elvax.

Lesion studies suggest that primary auditory cortex (A1) is required for accurate sound localization by carnivores and primates. In order to elucidate further its role in spatial hearing, we examined the behavioural consequences of reversibly inactivating ferret A1 over long periods, using Elvax implants releasing the GABA(A) receptor agonist muscimol. Sub-dural polymer placements were shown to deliver relatively constant levels of muscimol to underlying cortex for >5 months. The measured diffusion of muscimol beneath and around the implant was limited to 1 mm. Cortical silencing was assessed electrophysiologically in both auditory and visual cortices. This exhibited rapid onset and was reversed within a few hours of implant removal. Inactivation of cortical neurons extended to all layers for implants lasting up to 6 weeks and throughout at least layers I-IV for longer placements, whereas thalamic activity in layer IV appeared to be unaffected. Blockade of cortical neurons in the deeper layers was restricted to < or = 500 microm from the edge of the implant, but was usually more widespread in the superficial layers. In contrast, drug-free Elvax implants had little discernible effect on the responses of the underlying cortical neurons. Bilateral implants of muscimol-Elvax over A1 produced significant deficits in the localization of brief sounds in horizontal space and particularly a reduced ability to discriminate between anterior and posterior sound sources. The performance of these ferrets gradually improved over the period in which the Elvax was in place and attained that of control animals following its removal. Although similar in nature, these deficits were less pronounced than those caused by cortical lesions and suggest a specific role for A1 in resolving the spatial ambiguities inherent in auditory localization cues.

The receptive-field organization of simple cells in primary visual cortex of ferrets under natural scene stimulation.

The responses of simple cells in primary visual cortex to sinusoidal gratings can primarily be predicted from their spatial receptive fields, as mapped using spots or bars. Although this quasilinearity is well documented, it is not clear whether it holds for complex natural stimuli. We recorded from simple cells in the primary visual cortex of anesthetized ferrets while stimulating with flashed digitized photographs of natural scenes. We applied standard reverse-correlation methods to quantify the average natural stimulus that invokes a neuronal response. Although these maps cannot be the receptive fields, we find that they still predict the preferred orientation of grating for each cell very well (r = 0.91); they do not predict the spatial-frequency tuning. Using a novel application of the linear reconstruction method called regularized pseudoinverse, we were able to recover high-resolution receptive-field maps from the responses to a relatively small number of natural scenes. These receptive-field maps not only predict the optimum orientation of each cell (r = 0.96) but also the spatial-frequency optimum (r = 0.89); the maps also predict the tuning bandwidths of many cells. Therefore, our first conclusion is that the tuning preferences of the cells are primarily linear and constant across stimulus type. However, when we used these maps to predict the actual responses of the cells to natural scenes, we did find evidence of expansive output nonlinearity and nonlinear influences from outside the classical receptive fields, orientation tuning, and spatial-frequency tuning.

Relay of visual information to the lateral geniculate nucleus and the visual cortex in albino ferrets.

The abnormal organization of the central visual pathways in the albino ferret has been characterized anatomically and physiologically. Recordings in dorsal lateral geniculate nucleus of the albino ferret show that lamina A1, which receives an aberrant projection from the contralateral eye, contains an extensive representation of the ipsilateral visual hemifield with receptive fields located up to 35 degrees from the vertical meridian. This is not the case in pigmented ferrets, for which the vast majority of units, activated through either the contralateral or ipsilateral eye, have receptive fields confined to the contralateral hemifield. The few fields found in the ipsilateral hemifield are driven through the contralateral eye and none is more than 10 degrees from the midline. Cortical topography was studied by making closely spaced electrode penetrations across the area 17/18 border. In pigmented animals, the reversal of topography at the border is characterized by units with receptive fields centered a few degrees into the ipsilateral hemifield. In 22 of 25 albinos, the "Boston" aberrant topography was found: the representation of the vertical meridian is within area 17, rather than at the area 17/18 border. Instead, at the area 17/18 border, there is a reversal in the topographic progression at up to 30 degrees into the ipsilateral hemifield. This pattern was most pronounced in the upper visual field. In agreement with the "Boston" physiology, injections of retrograde tracer made in area 17 usually label neurons in either lamina A or the part of lamina A1 that is aberrantly innervated by the contralateral eye. A column of labeled cells extending through all geniculate layers is rarely seen in albinos, although this is commonly the pattern in pigmented ferrets.