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A Hendrickson

Publications and source records attributed to A Hendrickson.

At least 19 recordsLinked to original sources
PubMed2006

Co-localization of glycine and gaba immunoreactivity in interneurons in Macaca monkey cerebellar cortex.

Previous work demonstrates that the cerebellum uses glycine as a fast inhibitory neurotransmitter [Ottersen OP, Davanger S, Storm-Mathisen J (1987) Glycine-like immunoreactivity in the cerebellum of rat and Senegalese baboon, Papio papio: a comparison with the distribution of GABA-like immunoreactivity and with [3H]glycine and [3H]GABA uptake. Exp Brain Res 66(1):211-221; Ottersen OP, Storm-Mathisen J, Somogyi P (1988) Colocalization of glycine-like and GABA-like immunoreactivities in Golgi cell terminals in the rat cerebellum: a postembedding light and electron microscopic study. Brain Res 450(1-2):342-353; Dieudonne S (1995) Glycinergic synaptic currents in Golgi cells of the rat cerebellum. Proc Natl Acad Sci U S A 92:1441-1445; Dumoulin A, Triller A, Dieudonne S (2001) IPSC kinetics at identified GABAergic and mixed GABAergic and glycinergic synapses onto cerebellar Golgi cells. J Neurosci 21(16):6045-6057; Dugue GP, Dumoulin A, Triller A, Dieudonne S (2005) Target-dependent use of coreleased inhibitory transmitters at central synapses. J Neurosci 25(28):6490-6498; Zeilhofer HU, Studler B, Arabadzisz D, Schweizer C, Ahmadi S, Layh B, Bosl MR, Fritschy JM (2005) Glycinergic neurons expressing enhanced green fluorescent protein in bacterial artificial chromosome transgenic mice. J Comp Neurol 482(2):123-141]. In the rat cerebellum glycine is not released by itself but is released together with GABA by Lugaro cells onto Golgi cells [Dumoulin A, Triller A, Dieudonne S (2001) IPSC kinetics at identified GABAergic and mixed GABAergic and glycinergic synapses onto cerebellar Golgi cells. J Neurosci 21(16):6045-6057] and by Golgi cells onto unipolar brush and granule cells [Dugue GP, Dumoulin A, Triller A, Dieudonne S (2005) Target-dependent use of coreleased inhibitory transmitters at central synapses. J Neurosci 25(28):6490-6498]. Here we report, from immunolabeling evidence in Macaca cerebellum, that interneurons in the granular cell layer are glycine+ at a density of 120 cells/linear mm. Their morphology indicates that they include Golgi and Lugaro cell types with the majority containing both glycine and GABA or glutamic acid decarboxylase. These data are consistent with the proposal that, as in the rat cerebellum, these granular cell layer interneurons corelease glycine and GABA in the primate cerebellum. The patterns of labeling for glycine and GABA within Golgi and Lugaro cells also indicate that there are biochemical sub-types which are morphologically similar. Further, we find that glycine, GABA and glutamic acid decarboxylase identified candelabrum cells adjacent to the Purkinje cells which is the first time that this interneuron has been reported in primate cerebellar cortex. We propose that candelabrum cells, like the majority of Golgi and Lugaro cells, release both glycine and GABA.

Animals↗
PubMed2001

Multiple phosphorylated isoforms of NRL are expressed in rod photoreceptors.

NRL, a bZIP transcription factor of the Maf subfamily, interacts with the homeodomain protein CRX and synergistically regulates rhodopsin expression. Here we report that six isoforms of NRL (29-35 kDa) are generated by phosphorylation and expressed specifically in the mammalian retina. The anti-NRL antibody also cross-reacts with a cytosolic 45-kDa protein, which is detected in neuronal tissues but is not encoded by the NRL gene. In both human retinal cell cultures and sections of fetal and adult human retina, NRL is present in the nuclei of developing and mature rods but not cones. We propose that NRL regulates rod photoreceptor-specific gene expression and is involved in rod differentiation.

Alkaline Phosphatase↗
PubMed2001

Localization of pigment epithelium derived factor (PEDF) in developing and adult human ocular tissues.

PURPOSE: To localize pigment epithelium-derived factor (PEDF) in developing and adult human ocular tissues. METHODS: PEDF was localized in fetal and adult eyes by immunofluorescence with a polyclonal antibody (pAb) against amino acids 327-343 of PEDF, or a monoclonal antibody (mAb) against the C-terminal 155 amino acids of PEDF. Specificity of the antibodies was documented by Western blotting. PEDF mRNA was localized in adult retina by in situ hybridization. RESULTS: In developing retinas (7.4 to 21.5 fetal weeks, Fwks), pAb anti-PEDF labeled retinal pigment epithelium (RPE) granules, developing cones, some neuroblasts and many cells in the ganglion cell layer (GCL). In adult retinas, pAb anti-PEDF labeled rod and cone cytoplasm and nuclei of rods but not cones. Cells in the INL and GCL, choroid, corneal epithelium and endothelium, and ciliary body were also pAb PEDF-positive. Preadsorption of pAb anti-PEDF with the immunizing peptide blocked specific labeling in retina and other tissues, except for photoreceptor outer segments. In agreement with the immunolocalization with pAb anti-PEDF, in situ hybridization revealed PEDF mRNA in the RPE, photoreceptors, inner nuclear layer cells and ganglion cells in adult retina. In developing retinas 18 Fwks and older, and in adult retinas, mAb anti-PEDF labeled the interphotoreceptor matrix (IPM). Western blots of retina, cornea, and ciliary body/iris with pAb anti-PEDF produced several bands at about 46 kDa. With mAb anti-PEDF, retina produced one band at about 46 kDa; cornea and ciliary body/iris had several bands at about 46 kDa. CONCLUSIONS: PEDF, originally reported as a product of RPE cells, is present in photoreceptors and inner retinal cell types in developing and adult human eyes. Photoreceptors and RPE may secrete PEDF into the IPM.

Aged↗
PubMed2001

Regulation of retinal capillary cells by basic fibroblast growth factor, vascular endothelial growth factor, and hypoxia.

Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) feature prominently in retinal neovascular diseases. Although the role of VEGF in retinal angiogenesis is well established, the importance of bFGF in this process requires further clarification. This study was undertaken to investigate the responses of retinal capillary cells (endothelial cells and pericytes) to bFGF under hypoxic conditions, as well as the potentially synergistic effects of bFGF and VEGF on the proliferation and cord formation of retinal endothelial cells. Cell proliferation was determined by cell number and by 3H-thymidine incorporation. Cord formation was assessed in three-dimensional gels of collagen type I. VEGF and bFGF increased 3H-thymidine incorporation by both cell types, an effect that was more pronounced in a hypoxic environment. Moreover, the proliferation of pericytes was stimulated to a greater extent by bFGF relative to VEGF. Endothelial migration in collagen gels, however, was induced more effectively by VEGF than by bFGF. A synergistic effect of VEGF and bFGF on cell invasion was observed in the collagen gel assay. VEGF and bFGF each augment proliferation of these cells, especially under hypoxia. We thus propose that these two cytokines have a synergistic effect at several stages of angiogenesis in the retina.

Animals↗
PubMed2001

Immunocytochemical characterization of cysts in the peripheral retina and pars plana of the adult primate.

PURPOSE: To better characterize the cellular constituents of cysts in the peripheral retina and pars plana of the adult monkey. METHODS: Frozen sections of the peripheral retinal margin and pars plana from monkeys (Macaca nemestrina) between 1 and 15 years of age were stained with toluidine blue or immunolabeled with a variety of glia- and neuron-specific antibodies. RESULTS: In animals 1 to 2 years of age, the nonpigmented inner layer of the pars plana is a pseudostratified columnar epithelium. In these young animals, the peripheral retina had distinct layers and did not contain cysts. In animals 6 years of age or older, there were numerous cysts in the pars plana and in the peripheral retina. In the peripheral retina, neurons were randomly distributed and did not have a laminar organization. Cells surrounding cysts were immunoreactive for different types of markers for retinal neurons. Some of the cells surrounding cysts in the pars plana were also unexpectedly immunoreactive for antigens normally expressed only in retinal neurons and glia. CONCLUSIONS: Cysts form in the peripheral retina and pars plana in adult monkeys. The peripheral retinal cysts disrupt the normal lamination of the cells, but all types of retinal neurons are still present in the cysts. In an unexpected finding, cysts in the pars plana also contained cells immunoreactive for a few of the markers of retinal cells, suggesting that neurogenesis may occur in the pars plana of the adult primate.

Aging↗
PubMed2000

Spatial and temporal expression of short, long/medium, or both opsins in human fetal cones.

Human cone photoreceptors are characterized by long (L), medium (M), or short (S) wavelength-specific opsin. No reports have described the developmental pattern of human cone opsin expression, nor has the existence of human cones containing more than one opsin been tested. Single-and double-label immunocytochemistry and in situ hybridization have been used to determine the developmental pattern of opsin appearance and to investigate the presence of double-labeled cones in sections and wholemounts of human fetal, neonatal, infant, and adult retina. S opsin protein appears in and around the fovea at fetal week (Fwk) 10.9, whereas L/M opsin first appears in the fovea at Fwk 14-15. S opsin mRNA and protein are consistently detected much farther into peripheral retina than L/M opsin, indicating that S appears before L/M opsin. S cones cover 90% of the retina by Fwk 19. L/M cones appear outside the central retina by Fwk 21.5 and reach the retinal edge by Fwk 34-37. The spatial pattern of mRNA expression closely matches that for protein, but mRNA appears slightly earlier than protein at a given retinal point, indicating that only short delays occur between mRNA expression and translation into protein. Cones containing both S and L/M opsin (S+L/M) appear around the fovea shortly after L/M opsin is expressed, are found in more peripheral retina at older ages, and decrease in number after birth. Some S+L/M cones are still detected in adult retina. Both S opsin protein and mRNA appear significantly earlier than L/M mRNA or protein across the human retina, suggesting that the two cone types differentiate under independent controlling factors. However, the presence of single cones containing both S and L/M opsin during development suggests that human cones can respond to the factors controlling expression of each opsin.

Aging↗
PubMed2000

Nocturnal tarsier retina has both short and long/medium-wavelength cones in an unusual topography.

The evolutionary position of tarsiers with respect to primates is still debated. The type of photoreceptors in the nocturnal Tarsius spectrum retina has been compared with the nocturnal New World monkey Aotus trivulgaris and the Old World monkey Macaca nemestrina by using immunocytochemical labeling for antisera known to be specific for primate cone and rod proteins. In all three species, antisera to long/medium (L/M) -wavelength specific cone opsin and cone-specific alpha-transducin detected a single row of cones. Only Macaca and tarsier retina contained cones labeled by antiserum to short (S) -wavelength specific cone opsin. Tarsier rod cell bodies were 6-12 deep, depending on retinal eccentricity. Tarsier central cones had 2-microm-wide outer (OS) and inner segments, which came straight off the cell body. Cone morphology differed little from rods except OS were shorter. Macaca cones labeled for 7G6 and calbindin, Aotus cones did not label for calbindin, and Tarsius cones did not label for 7G6 or calbindin. In tarsier retinal whole-mounts, peak cone density ranged from 11,600-14,200/cones mm(2). The 11- to 12-mm-wide peak region centered roughly on the optic disc, although foveal counts remain to be completed. Density decreased symmetrically to a far peripheral band of 4,200-7, 000/cones mm(2). In contrast, S cone density was very low in central retina (0-300/mm(2)), rose symmetrically with eccentricity, and peaked at 1,100-1,600/mm(2) in a 2- to 3-mm-wide zone in the far periphery. In this zone, S cones were 9-14% of all cones. L/M cones were regularly spaced, whereas S cones showed no regular distribution pattern. Although the functional characteristics of the tarsier S and L/M cone systems are yet to be determined, tarsier cone proteins and distribution have some similarities to both New and Old World monkey retinas.

Animals↗
PubMed2000

The spatial and temporal expression of outer segment proteins during development of Macaca monkey cones.

PURPOSE: To characterize the spatial and temporal expression of key structural and phototransduction cascade proteins in the monkey cone outer segment (OS). METHODS: Retinas from Macaca monkeys from ages fetal day (Fd) 89 through adulthood were double labeled using immunofluorescence for short (S) or long/medium (L/M) wavelength-sensitive cone opsin and either a structural protein (peripherin) or a phototransduction cascade protein (alpha-transducin [alpha-T], phosphodiesterase [PDE], or rhodopsin kinase [RK]). The spatial and temporal patterns of expression for each protein at each age were determined and graphed as a percentage of retinal coverage. RESULTS: In both cone types, opsins and phototransduction proteins appear first in the fovea and last at the retinal edge. Peripherin appears concomitantly with opsin in both S and L/M cones, but S cones express peripherin and opsin 1 to 3 weeks before neighboring L/M cones. Alpha-T, PDE, and RK are expressed together in the L/M cone OS shortly after L/M opsin appears. Phototransduction proteins are not expressed in S cones until 1 to 3 weeks after the appearance of S opsin and at the same time that neighboring cones are expressing both L/M opsin and phototransduction proteins. CONCLUSIONS: The concomitant appearance of opsin and peripherin strongly suggests roles in promoting the structural integrity of the developing OS. Phototransduction cascade proteins appear in the developing OS at the same time as one another, but after opsin. The significant lag between their expression and that of S cone opsin indicates that phototransduction proteins are not essential for OS formation, nor does opsin expression trigger their expression. The different temporal but similar spatial expression patterns of phototransduction proteins within S and L/M cones suggests that some local signal(s) coordinates their appearance.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1999

Distribution and development of short-wavelength cones differ between Macaca monkey and human fovea.

Macaca monkey and humans have three cone types containing either long-wavelength (L), medium-wavelength (M), or short-wavelength (S)-specific opsin. The highest cone density is found in the fovea, which mediates high visual acuity. Most studies agree that the adult human fovea has a small S cone-free area, but data are conflicting concerning S-cone numbers in the adult Macaca monkey fovea, and little evidence exists for how either primate fovea develops its characteristic cone pattern. Single- and double-label in situ hybridization and immunocytochemistry have been used to determine the pattern of foveal S cones in both the fetal and adult Macaca and human. Both labels find a clear difference at all ages between monkey and human. Adult humans have a distinct but variable central zone about 100 microm wide that lacks S cones and is surrounded by a ring in which the S-cone density is 8%. This S cone-free zone is detectable at fetal week 15.5 (Fwk15.5), shortly after S opsin is expressed, and is similar to the adult by Fwk20.5. Adult monkey foveas have an overall S-cone foveal density of 10%, with several areas lacking a few S cones that are not coincident with the area of highest cone density. A surrounding zone at 200-microm eccentricity has an S-cone density averaging 25%, but, by 800 microm, this has decreased to 11%. Fetal day 77-135 monkeys all have a distribution and density of foveal S cones similar to adults, although the high-density ring is not obvious in fetal retinas. Estimates of the numbers of S cones missing in the fetal human fovea range from 234 to 328, whereas no more than 40 are missing in the fetal monkey. These results show that, in these two trichromatic primates, S-cone distribution and the developmental mechanisms determining S-cone topography are markedly different from the time that S cones are first detected.

Adult↗
PubMed1999

Analysis of chicken Wnt-13 expression demonstrates coincidence with cell division in the developing eye and is consistent with a role in induction.

We used a degenerate polymerase chain reaction (PCR) strategy to search for Wnt RNA in developing ocular tissues. We isolated a Macaca monkey Wnt-13 PCR fragment, orthologous to the human and murine Wnt-13 and Xenopus Wnt-2b, and a chick Wnt13 cDNA. Wnt-13 is a member of the Wnt-1 class of transforming Wnt molecules. In situ RNA hybridization revealed a dynamic Wnt-13 expression pattern in numerous developing tissues. Within the eye, Wnt-13 is expressed in the proliferative epithelium of the lens and both pigmented and non-pigmented layers of the ciliary margin. In vitro BrdU incorporation studies coupled with in situ hybridization showed that cWnt-13 expression domains in the lens were coincident with cell division. In addition to the eye, cWnt-13 was expressed in head ectoderm, prospective forelimb mesenchyme, lung bud, pharyngeal arches, the brain, as well as the otic vesicle. Our data are consistent with previous observations linking transforming Wnts with cell division and implicate a cascade of events involving cWnt-13 first in dorsoventral patterning and later in cell proliferation regulation associated with lens development. Dev Dyn 1999;215:215-224.

Amino Acid Sequence↗
PubMed1999

Flavor-cued modulation of intake in rats: role of familiarity and impact on 24-h intake.

Following training with distinctively flavored nutritive solutions that differ in concentration and thus in caloric value, rats demonstrate flavor-postingestive consequence learning by preferentially consuming one of the flavors in two-bottle tests (both flavors in nutrient-identical solutions.) Experiment 1 investigated whether the relative familiarity of the flavor-nutrient combinations encountered in two-bottle tests contributes to the observed preference. One of the training concentrations (rather than the customary intermediate concentration) was used to present the flavors in testing; thus, one of the flavors was in a familiar context while the other was in an unfamiliar context. The results of two independent trials (rats trained with 1 and 5% sucrose; rats trained with 5 and 40% sucrose) confirmed that two-bottle test preference was not a preference for the familiar flavor-nutrient combination. Experiment 2 examined whether caloric expectancies based upon a previously learned flavor-postingestive consequence association would affect total daily intake. On alternating days, rats consumed 30 mL of dilute (5%) and concentrated (40%) sucrose, each distinctively flavored. When given 30 mL of 22.5% sucrose containing each of the flavors on separate test days, they ate less chow and thus fewer total calories over 24 h when given the flavor previously paired with concentrated sucrose. Experiment 3 replicated the design of Experiment 2 except that fat calories were used instead of sucrose; no significant adjustment of chow intake in extinction tests was noted, even when the number of fat calories used in training was increased (Experiment 4). Thus, rats did not exhibit flavor-cued modulation of chow intake when trained with fat, in contrast to responsivity to flavor cues when trained with sucrose. This differential responding to fat versus carbohydrate calories is consistent with previous observations, in a variety of paradigms, that modulation of caloric intake is less energetically appropriate when ingested foods are high in fat relative to high-carbohydrate foods.

Animals↗
PubMed1997

Spatial and temporal expression of cone opsins during monkey retinal development.

The primate retina requires a coordinated series of developmental events to form its specialized photoreceptor topography. In this study, the temporal expression of cone photoreceptor opsin was determined in Macaca monkey retina. Markers for mRNA and protein that recognize short wavelength (S) and long/medium wavelength (L/M) opsin were used to determine (1) the temporal and spatial patterns of opsin expression, (2) the spatial relationship between S and L/M cones at the time of initial opsin expression, and (3) the relative time of cone and rod opsin expression (Dorn et al. [1995] Invest. Ophthalmol. Vis. Sci. 36:2634-2651). Adult cone outer segments were recognized by either L/M or S opsin antiserum. Of all adult cone inner segments, 88-90% contained L/M opsin mRNA, whereas 10-12% contained S opsin mRNA. Fetal cones initially showed cell membrane as well as outer segment labeling for opsin protein, but cell membrane labeling disappeared by birth. No cones at any age contained markers for both S and L/M opsin mRNA or protein. S and L/M opsin protein appeared in the fovea at fetal day 75. Once opsin expression progressed beyond the fovea, both mRNA and protein for S opsin were consistently detected more peripherally than L/M opsin. Cones at the peripheral edge of S opsin expression had basal telodendria that appeared to reach toward neighboring cones. Because interactions between cone populations could organize the cone mosaic, the spatial relationship between S cones and the first cones to express L/M protein was analyzed quantitatively by using double-label immunocytochemistry. No consistent relationship was found between these two cone populations. Cones are generated at least 1 week before rods across monkey retina. However, rod opsin protein appears in and around the fovea at fetal day 66, 1 week before cone opsin protein. This suggests that independent local factors control differentiation in these two photoreceptor populations.

Aging↗
PubMed1996

Parvalbumin, calbindin, and calretinin mark distinct pathways during development of monkey dorsal lateral geniculate nucleus.

Immunocyochemical labeling was applied to follow the developmental changes in the calcium-binding proteins parvalbumin (PV), calbindin D28k (CaB), and calretinin (CaR) during fetal and infant development of Macaca monkey dorsal lateral geniculate nucleus (LGN). For all three proteins, LGN cell body and retinal ganglion cell (RGC) axon labeling patterns changed temporally and spatially over development, and many of these were LGN laminar specific. CaR+ and CaB+ cells were present at the youngest age studied, fetal day 55 (F55). After lamination of the LGN occurred between F90 and F115, CaR+ and CaB+ neurons were specific markers for the S, intercalated, and interlaminar layers. Double label immunocytochemistry showed that all CaR+ cells contained CaB, and none contained GABA. CaR+ cell bodies decreased in number soon after birth so that adult LGN contained only a very small number of CaR+ cells. These patterns and cell counts indicated that a downregulation of CaR had occurred in the CaB+ population. Although CaB+ cell density in S and interlaminar zones declined in the adult, cell counts indicated that this is due to dilution of a stable population into a much larger nucleus during development. PV+ cells appeared at F85 only within the putative magnocellular (M) and parvocellular (P) layers, and PV remained a marker for these layers throughout development. Fetal PV cells also contained GABA, indicating that they were LGN interneurons. After birth, GABA-/PV+ cell numbers increased dramatically throughout the whole nucleus so that by the end of the first year, P and M layers were filled with PV+ cells. Their number and size indicated that these were the LGN projection neurons. Beginning at F66, bundles of PV+ axons occupied the anterior-middle LGN and filled the optic tract. Up to F101, PV+ synaptic terminals were restricted to Players, but after F132 labeling in M layers was heavier than in P layers. Axonal labeling for CaR began at F125. Prenatally CaR+ terminals were present mainly in P layers, whereas by postnatal 9 weeks labeling in M layers much exceeded P layers. Axonal labeling for CaB was present at F132, but CaB+ terminals were observed only after birth with labeling always heavier in M than P layers. By postnatal 9 weeks, PV, CaR, and CaB were colocalized in the same axons and terminals. These experiments indicated that during development and in the adult LGN, both CaR and CaB were markers for the LGN neurons in the S and intercalated pathway. CaR was present transiently while CaB persisted into adulthood. PV was a M and P layer marker first for interneurons and later for projection cells. The complex temporal developmental patterns found in this study suggested that viewing PV, CaB, and CaR simply as calcium-buffering proteins severely underestimates their functional roles during visual system maturation.

Age Factors↗
PubMed1996

Detection of MAO-A and MAO-B mRNAs in monkey brainstem by cross-hybridization with human oligonucleotide probes.

The distribution of mRNAs encoding the isoenzymes monoamine oxidase A and B (MAO-A and MAO-B) in monkey locus coeruleus and dorsal raphe nucleus was studied by in situ hybridization histochemistry using 35S-labelled oligodeoxynucleotide probes complementary to cloned human sequences. MAO-A mRNA was highly expressed in noradrenergic neurons of the locus coeruleus while MAO-B mRNA was abundantly and exclusively localized in serotoninergic neurons of the raphe. However, upon emulsion radioautography raphe neurons showed a level of MAO-A mRNA signal noticeably above the background. Our results indicate the utility of human MAO oligodeoxynucleotide probes to identify homologous species of transcripts in the brain of a non-human primate. They also suggest the coexistence of the isoenzymes in raphe neurons as well as the potential role of MAO-A in metabolizing serotonin in vivo.

Animals↗
PubMed1994

Light and electron microscopic analysis of synaptic development in Macaca monkey retina as detected by immunocytochemical labeling for the synaptic vesicle protein, SV2.

The development of synapses has been followed in Macaca monkey fetal and infant retina using immunocytochemical labeling for the transmembrane synaptic vesicle glycoprotein, SV2. Electron microscopy (EM) was used to verify the presence of morphological synapses at selected ages. EM immunocytochemical labeling in adult retina showed that all synaptic types contained SV2 in inner (IPL) and outer (OPL) plexiform layers. In fetal retina, SV2 expression and the appearance of morphological synapses were closely related in time, demonstrating that SV2 is a reliable marker for synaptogenesis. SV2 expression appears along a foveal to peripheral gradient. Both SV2 and synapses appear in the foveal IPL at Fd50-55, and reach the retinal edge by Fd90-103. Cone ribbon synapses and SV2 labeling are not present in the foveal OPL until Fd60. Photoreceptors in the far periphery contain SV2 by Fd119-125. This pattern demonstrates an "inner to outer" direction of synaptogenesis. Cones show SV2 labeling before rods at the same retinal eccentricity. In the cone-dominated fovea, SV2 labeling and bipolar cell ribbon-containing terminals are present at Fd55 when amacrine cell conventional terminals are very scarce, indicating that bipolar synapses precede amacrine synapses in monkey foveal IPL. SV2 labeling and bipolar terminals appear first in the outer IPL which contains "OFF" ganglion and bipolar processes in the adult, suggesting that "OFF" midget bipolar cells may form the first synapses. Both SV2 immunocytochemical labeling and EM morphology find that monkey retina follows a generalized inner before outer, and cone before rod synaptic developmental pattern, similar to that in other mammals. The cone-dominated fovea initiates synaptogenesis, and shows a different synaptic sequence from rod-dominated peripheral retina.

Animals↗
PubMed1994

Coincidental appearance of the alpha 1 subunit of the GABA-A receptor and the type I benzodiazepine receptor near birth in macaque monkey visual cortex.

The expression of subtypes of the GABA-A/benzodiazepine receptor complex has been studied during pre- and postnatal development of Macaca monkey visual cortex using complementary radioligand and immunocytochemical labeling. Type I benzodiazepine receptors were labeled directly by [3H]zolpidem. Type II receptors were determined by the amount of binding for [3H]flunitrazepam (FZ) persisting in the presence of the type I-specific ligand CL218872. Monoclonal antibody bd24 was used to label alpha 1 subunits and bd17 to label beta 2 and beta 3 subunits of the GABA-A receptor. Radioligand binding data and bd17 immunoreactivity indicated that type II benzodiazepine receptors were present by fetal day (Fd) 74 (44% of gestation). Immunoreactivity for the beta 2/beta 3 subunits increased until 3-6 weeks after birth, and then declined somewhat into adulthood. Neither radioligand labeling for type I receptors nor immunocytochemical staining for the alpha 1 subunit were apparent until mid-gestation. Both markers appeared shortly before birth in layer 4C, and then in other cortical layers after birth. Immunoreactivity for the alpha 1 subunit increased steadily after birth until it became more intense than that for beta 2/3 subunits in the adult. Quantitative densitometry of CL218872 competition for [3H]FZ binding showed that type I/II distribution was 22%/78% at Fd103; 42%/58% at Fd131; 67%/33% at 9 months; and 61%/39% in adult visual cortex. This "switch" between benzodiazepine receptor subtypes overlaps the postnatal critical period for geniculostriate development, suggesting that the change from type II to type I receptors and the appearance of alpha 1 subunits may play a decisive role in the maturation of geniculocortical axon terminations and cortical response properties. It remains to be shown whether this "switch" is dependent on functional visual input.

Animals↗
PubMed1992

The development of parafoveal and mid-peripheral human retina.

The morphological development of parafoveal retina (1-1.5 mm from the foveal center) and the mid-peripheral (4 mm from the foveal center) human retina has been studied from fetal (F) 26 weeks to adulthood. At both retinal points, all layers and neuronal types are present at F26 weeks. In parafovea at F26 weeks photoreceptors have only a rudimentary inner segment and no outer segments. Short outer segments are present on both rods and cones at F36 weeks. By postnatal (P) 5-8 days the inner retina is relatively mature. Photoreceptors have elongated basal axons which cause the photoreceptor layer to become much thicker than in prenatal retina. At birth cone inner segments are untapered, but rod inner segments have already reached their adult width of 2 microns. Both rod and cone inner and outer segments are 30-50% of adult length. By 13 months both inner and outer retina are mature appearing, with the photoreceptors accounting for half the retinal thickness due to the elongation of the fibers of Henle. Cone outer segments elongate up to P5 years and rod outer segments to P13 years. At mid-peripheral or rod-ring retina outer segments are present on rods at F26 weeks and on cones at F36 weeks. At birth the inner retina is adultlike. The outer plexiform layer becomes thicker up to P45 months due to the elongation of fibers of Henle. At birth both rod and cone mid-peripheral inner segments are slightly longer and outer segments are 50% longer than in parafoveal retina. By P5 years mid-peripheral rod outer segments are slightly longer than in parafoveal retina, and this changes little thereafter. This anatomical study has found that the photoreceptors in peripheral rod-ring retina develop earlier than those in more central retina, and in turn parafoveal photoreceptors develop well in advance of foveal cones. This suggests that human neonates may utilize more peripheral retinal regions for some aspects of visual function before foveal cone vision becomes dominant.

Adolescent↗