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SummaryAxon terminals from the two eyes initially overlap in the dorsal-lateral geniculate nucleus (dLGN) but subsequently refine to occupy nonoverlapping territories. Retinal activity is required to establish and maintain this segregation. We show that despite the presence of retinal activity, segregated projections desegregate when the structure of activity is altered. Early in development, spontaneous retinal activity in the no b-wave (nob) mouse is indistinguishable from that of wild-type mice, and eye-specific segregation proceeds normally. But, around eye-opening, spontaneous and visually evoked activity in nob retinas become abnormal, coincident with a failure to preserve precise eye-specific territories. Dark-rearing studies suggest that altered visual experience is not responsible. Transgenic rescue of the mutated protein (nyctalopin) within nob retinal interneurons, without rescuing expression in either retinal projection neurons or their postsynaptic targets in the dLGN, restores spontaneous retinal activity patterns and prevents desegregation. Thus, normally structured spontaneous retinal activity stabilizes newly refined retinogeniculate circuitry.

Author(s): Sagdullaev, Botir T; Aramant, Robert B; Seiler, Magdalene J; Woch, Gustaw; McCall, Maureen A | Abstract: PURPOSE:To map the spatiotemporal decline in retinally driven activity in the superior colliculus (SC) of transgenic S334ter-line-3 rats that express a mutated rhodopsin, which causes photoreceptor degeneration. To determine whether transplantation of fetal retinal sheets into the subretinal space of these rats can recover visual activity in the SC. METHODS:A visual stimulus was presented to the eye, and responses were recorded across the SC of untreated S334ter-line-3 rats aged 28 to 288 days. These data were used to draw a map of the developing scotoma. Intact retinal sheets from embryonic day 19 rats were transplanted into the subretinal space of S334ter-line-3 rats between 21 and 28 days of age. Responses to retinal stimulation were mapped in the SC of transplanted and sham control rats 78 to 163 days after surgery. The morphology of the retinas in all groups was examined. RESULTS:Photoreceptor cell loss in untreated rats matched the decline in visual activity in the SC. At 28 days, there was a scotoma in the area of the SC that represents the central retina and, by 63 days, it had enlarged to cover the entire retinal representation. Visual responses were evoked in 64% of rats with retinal transplants. These retinally driven responses were confined to a small, contiguous region of the SC that represents the sector of the retina where the transplant was placed. Visual responses were absent in the SC outside this area in transplant recipients and throughout the SC of untreated and sham control rats. CONCLUSIONS:Transplantation of fetal retinal sheets induced recovery of visual activity in the SC in this model of RP. The mechanisms underlying this functional recovery remain to be resolved, but these results suggest that transplantation should be further explored as a therapy for RP.

Purpose Interactions between vasculature and neurons provide important insight into the function of the nervous system, as well as into neurological diseases wherein these interactions are disrupted. This study characterizes a previously unreported retinal vascular plexus and examines potential sites of neurovascular interaction. Methods Vascular, neuronal, and glial elements were visualized using immunohistochemical markers. The distribution of vascular layers was measured and compared across eccentricities. Intensity profiles were calculated from confocal image reconstructions to reveal the proximity of vasculature to neuronal and glial processes. Results Retinal vasculature forms a plexus that coincides with the dendritic processes of OFF cholinergic amacrine cells within the inner plexiform layer. Across eccentricities, this plexus comprises approximately 8% of the total length of horizontally running blood vessels in the retina. Processes of Muller glia and OFF cholinergic amacrine cells colocalize with the blood vessels that form the intersublaminar plexus. Conclusions In the retina, vasculature lacks autonomic control, but shows efficient local regulation. Although the source of this regulation is unclear, these results suggest that cholinergic amacrine cells and Muller glia may interact with the intersublaminar plexus to influence vasomotor activity. This may indicate a key role in modulating reciprocal interactions between neuronal activity and blood flow.

The chemical composition of pepper has been rather well studied. Its olefactory properties, hot and spicy, are due to the presence of capsanoid alkaloids, the content of which ranges from 0.02 to 0.2%. The pericarp of the fruit also contains an alkaloid similar to coniine, solanine, small quantities of acids (citric and palmitic), fatty and essential oils, and salts of P, K, Ca. The seeds have a large percent of fatty oil. The fruits typically are rich in vitamins A and C (vitamin C up to 380 mg%; vitamin A, 9-12 mg%). Hot pepper is cultivated everywhere in Uzbekistan. The hot variety Margelanskii 330 has been adapted to the region. It chemical composition has not been studied. We studied the alkaloid content of this pepper species. The alcohol extract, which contains capsanoids, was chromatographed on a silica-gel column. A substance with mp 62-63':C was isolated from the benzene eluate. Its IR spectrum contains absorption bands of active H (3316 cm -l, NH, OH), amide carbonyl (1652 cm'l), an aromatic ring (1601-1558 cm-l), and an isolated double bond (973 cm-l). The PMR spectrum (CDCI3) exhibits a doublet at 0.84 ppm (6H), probably from a gemdimethyl group. Protons of an aromatic methoxyl appear at 3.78 ppm (3H). A sharp two-proton doublet is observed near 4.24 ppm, apparently due to a methylene bound to the aromatic ring and the NH of an amide. Olefinic protons appear as a triplet at 5.18-5.32 ppm (2H). Protons of the aromatic ring (3I-I) are found in the range 6.60-6.84 ppm as a multiplet. Four groups of multiplets at 1.00-2.24 ppm that partially overlap are assigned by us to four methylenes bound at one terminus, probably with a carbonyl (quartet, 2H, 1.78-2.00 ppm), and at the other, with a C of a double bond (triplet, 2H, 2.00-2.24 ppm). Two twoproton quartets that partially overlap each other (1.10-1.74 ppm) (-CH2-CH 2- group) are located further out. Two one-proton signals are seen at 5.55-5.85 ppm (OH, NH). The molecular mass of the alkaloid was found using mass spectra, where a peak for the molecular ion with m/z 305 (8.3%) was noted. The mass spectrum also contains a peak for a fragment with m/z 167 (21%), which corresponds to cleavage of a C-N bond and loss from M + of a fragment with m/z 137 accompanied by proton migration. The base peak occurs at m/z 68, which arises from cleavage of the C-C bond of the side chain and migration of a proton. Rather strong peaks with m/z 150 (58%), 137 (94%), and 112 (48%) are observed. These are logically formed based on the alkaloid structure. This is clearly illustrated in the mass-spectral fragmentation pattern of capsaicin shown in the scheme below: nu'Z 167 .ffz 112 m/z 68 I II ,-H u '+H I-H ~. , ' II '

PURPOSE. Subretinal prosthetics are designed to electrically stimulate second-order cells, replacing dysfunctional photoreceptors in diseases such as retinitis pigmentosa (RP). For functional vision to occur, this signal must also reach central visual structures. In the current study, a subretinally implanted prosthetic was evaluated in the Royal College of Surgeons (RCS) rat model of RP, to determine its capacity to activate the retinotectal pathway. METHODS. Prosthetic implants were placed in RCS and wildtype (WT) rats at 4 weeks of age and evaluated 3 months later. Control rats underwent sham surgery, implantation with inactive prosthetics, or no treatment. Implant- and visible-evoked responses were isolated and evaluated in the superior colliculus (SC). RESULTS. In WT and RCS rats with active prosthetics, implantdriven responses were found in 100% of WT and 64% of RCS rats and were confined to a small SC region that corresponded to the retinal sector containing the implant and differed from visible-evoked responses. In addition, visible-evoked responses were more robust at sites that received implant input compared to sites that did not. These effects were not seen in WT rats or RCS control animals; although a general trophic effect on the number of responsive sites was observed in all RCS rats with surgery compared to untreated RCS rats. CONCLUSIONS. Direct activation of the retina by a subretinal implant induces activity in the SC of RCS rats, suggesting that these implants have some capacity to replace dysfunctional photoreceptors. The data also provide evidence for implantinduced neurotrophic effects as a consequence of both its presence and its activity in the retina. (Invest Ophthalmol Vis Sci. 2007;48:916‐926) DOI:10.1167/iovs.06-0811

It is known that rose fruit contains biologically active compounds (vitamins B 2, C, K, and P, carotene, organic adds, flavonoids, and tannin substances), which are responsible for healing properties [1---6], but there is no information on their carbohydrate content. We have investigated the carbohydrate composition of the fi'uit of Rosa canina. A comparative study was made of the carbohydrate compositions of the fruit (FR), of an aqueous extract (AER), and of the pulp remaining after the production of the preparation Kholam~ (PR). As a result we found the compositions of the alcohol-soluble fraction (ASF), of the water-soluble polysaccharides (WSPSs), and of the pectin substances (PSs) (Table 1). The commintlted air--dry raw material (FR and PR) was treated with 82% alcohol (1:2) twice for 1 h each time at the boil, and the combined extracts were concentrated, giving the total ASF (Table 1). By paper chromatography of the ASF of the FR (system 1, butan-l-olmpyridine---water (6:4:3), Ffltrak FN-11 paper) we detected glucose and sucrose. The WSPSs were extracted with water at 20~ twice for 2 h each. The extracts were evaporated under vacuum and were precipitated with isopropyl alcohol (1:2) (see Table 1). The precipitate of WSPSs formed a light cream-colored water-soluble powder giving a negative reaction for starch with iodine. The aqueous extract from the rose was precipitated with alcohol. The supernatant liquid was evaporated, the yield of ASF was determined (9.1%), and this was separated preparatively by PC for the quantitative determination of glucose (63.1% ) and fructose (35.2%). The precipitate obtained was treated with water at 20~ for 2 h, giving the WSPSs (1.69% on the raw material). The insoluble part consisted of the pectin substances (0.47% on the raw material). In the products of complete acid hydrolysis ( 1 N H2SO 4, 36 h) of the FR and AER we detected (PC, system 1) glucose and fructose in mounts of 2.1, 97.8 and 3.7, 96.2%, respectively.

SummaryCa2+/calmodulin-mediated negative feedback is a prototypical regulatory mechanism for Ca2+-permeable ion channels. In olfactory sensory neurons (OSNs), such regulation on the cyclic nucleotide-gated (CNG) channel is considered a major mechanism of OSN adaptation. To determine the role of Ca2+/calmodulin desensitization of the olfactory CNG channel, we introduced a mutation in the channel subunit CNGB1b in mice that rendered the channel resistant to fast desensitization by Ca2+/calmodulin. Contrary to expectations, mutant OSNs showed normal receptor current adaptation to repeated stimulation. Rather, they displayed slower response termination and, consequently, reduced ability to transmit olfactory information to the olfactory bulb. They also displayed reduced response decline during sustained odorant exposure. These results suggest that Ca2+/calmodulin-mediated CNG channel fast desensitization is less important in regulating the sensitivity to recurring stimulation than previously thought and instead functions primarily to terminate OSN responses.