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D R Hocking

Publications and source records attributed to D R Hocking.

At least 19 recordsLinked to original sources
PubMed1999

Metabolic mapping of suppression scotomas in striate cortex of macaques with experimental strabismus.

Misalignment of the ocular axes induces double vision and rivalry. To prevent these unpleasant sensations, most subjects fixate preferentially with one eye and suppress entirely the deviating eye or else suppress portions of the visual field of either eye. To explore the mechanism of visual suppression, a divergent strabismus (exotropia) was induced in six normal, adult Macaca fascicularis by disinserting the medial rectus muscles. After 4-8 weeks, each animal was chaired to measure its exotropia and to determine its ocular fixation preference. Five of the monkeys developed a clearly dominant eye. It was injected with [(3)H]proline. Alternate sections from flat-mounts of striate cortex were then processed either for autoradiography to label the ocular dominance columns or for cytochrome oxidase (CO) to assess local metabolic activity. Two CO patterns were seen, often in the same cortex. The first consisted of thin dark columns alternating with wide pale columns. This pattern arose from reduced CO activity in the suppressed eye's monocular core zones and both eyes' binocular border strips. The second pattern consisted of thin pale bands from reduced metabolic activity in both eyes' border strips. The thin dark-wide pale CO pattern was more widespread in the three animals with a strong fixation preference. The dark CO columns usually fit in register with the ocular dominance columns of the fixating eye, suggesting that perception was suppressed in the deviating eye. In most animals, however, the correlation switched in peripheral cortex contralateral to the deviating eye, implying local suppression of the fixating eye's temporal retina (beyond 10 degrees), as reported in humans with divergent strabismus. In the two animals with a weak fixation preference, pale border strips were found within the central visual field representation in both hemispheres. This CO pattern was consistent with alternating visual suppression. These experiments provide the first anatomical evidence for changes in cortical metabolism that can be correlated with suppression scotomas in subjects with strabismus.

Animals↗
PubMed1998

Monocular core zones and binocular border strips in primate striate cortex revealed by the contrasting effects of enucleation, eyelid suture, and retinal laser lesions on cytochrome oxidase activity.

In primate striate cortex, geniculocortical afferents in layer IVc terminate in parallel stripes called ocular dominance columns. We propose that this segregation of ocular inputs generates a related but distinct columnar system of monocular core zones alternating with binocular border strips. Evidence for this functional parcellation was obtained by comparing the effects of enucleation, eyelid suture, and retinal laser lesions on cytochrome oxidase (CO) activity in eight macaques. Enucleation produced a high-contrast pattern of dark and light columns in layer IVc, corresponding precisely to the ocular dominance columns, whereas eyelid suture produced a low-contrast pattern of thin dark columns alternating with wide pale columns. [3H]Proline eye injection showed that the thin dark columns corresponded to the core zones of the open eye's ocular dominance columns. The wide pale columns resulted from loss of CO activity in the sutured eye's core zones and within both eyes' border strips. Loss of CO activity within both eyes' border strips suggested that these regions are binocular. To confirm our findings, we compared different CO patterns in the same cortex by making retinal laser lesions in four animals. They produced a CO pattern tantamount to "focal" enucleation, although contrast was low when laser damage was confined to the outer retina. CO levels in cortical scotomas remained severely depressed for months after retinal lesions, even when the other eye was enucleated. This observation provided little anatomical support for the notion of topographic plasticity after visual deafferentation. In a single human subject with macular degeneration, CO revealed a low-contrast pattern of ocular dominance columns, resembling the pattern in monkeys with laser-induced photoreceptor damage.

Aged↗
PubMed1997

Timing of the critical period for plasticity of ocular dominance columns in macaque striate cortex.

Visual deprivation induced by monocular eyelid suture, a laboratory model for congenital cataract, results in shrinkage of ocular dominance columns serving the closed eye. We performed monocular suture in macaques at ages 1, 3, 5, 7, and 12 weeks to define the critical period for plasticity of ocular dominance columns. After a minimum survival of 8 months, complete montages of [3H]proline-labeled columns were reconstructed from flat-mounts of striate cortex in both hemispheres. In any given monkey, visual deprivation induced the columns throughout striate cortex (V1) to retract the same distance from their original borders in layer IVcbeta. After deprivation, the widest columns remained in the foveal representation and along the V1/V2 border, where columns are widest in control animals. The narrowest deprived columns belonged to the ipsilateral eye, especially along the horizontal meridian and in the periphery, where columns are narrowest in control animals. At the earliest age that we tested (1 week), visual deprivation reduced the columns to fragments. These fragments always coincided with a cytochrome oxidase patch, or a short string of patches, in the upper layers. More severe column shrinkage occurred in layer IVcbeta (parvo) than layer IVcalpha (magno). The geniculate input to the patches in layer III (konio) appeared normal after deprivation, despite loss of CO activity. Surprisingly, the blind spot representation of the open eye was shrunken by monocular deprivation, although binocular competition is absent in this region. Our principal finding was that eyelid suture at age 1 week caused the most severe column shrinkage. With suture at later ages, the degree of column shrinkage showed a progressive decline. Deprivation commencing at age 12 weeks caused no column shrinkage. These results imply that primate visual cortex is most vulnerable to deprivation during the first weeks of life. Our experiments should provide further impetus for the treatment of children with congenital cataract at the earliest possible age.

Age Factors↗
PubMed1997

Chronotopic fiber reordering and the distribution of cell adhesion and extracellular matrix molecules in the optic pathway of fetal ferrets.

We have examined the age-related reordering of optic axons as they pass through the chiasmatic region in fetal ferrets. Proportions of young and old optic axons were determined from electron micrographs taken sequentially through the prechiasmatic nerve, chiasm, and tract. This "chronotopic" reordering of axons was shown to emerge gradually, beginning rostral to the fusion of the two optic nerves, but continuing to develop caudal to the chiasmatic midline. Segregation of young from old optic axons was most pronounced within the optic tract. We then compared the emergence of this fiber reorganization to the distribution of cell adhesion and extracellular matrix molecules and to the glial architecture within the pathway. Using immunohistochemistry, the distributions of the cell adhesion molecules L1, NCAM, and TAG-1 and the extracellular matrix molecules laminin-1 and chondroitin sulfate proteoglycans (CSPGs) were determined. Among these, only the distribution of CSPGs was observed to change in a manner that complemented the segregation of young from old optic axons. CSPGs were densest in the deeper parts of the optic tract, coincident with radial glial fibers that turn to course within the region of the oldest optic axons. Both the glial architecture and the CSPG distribution form as a consequence of the invasion of the first optic axons, shown by the developmental sequence of each, and by the fact that these glial and molecular features fail to form in the absence of optic axons. The data suggest a model in which the gradient of CSPGs across the depth of the tract contributes to the formation of the chronotopic fiber reordering by providing a relatively unfavorable environment for subsequent axonal growth. The CSPGs may do so by interfering with adhesion molecules on optic axons that normally promote elongation.

Animals↗
PubMed1997

Myelin patterns in V1 and V2 of normal and monocularly enucleated monkeys.

A pattern of alternating light and dark columns was observed in wet, unstained sections of macaque striate cortex after monocular enucleation. The columns were clearest in layer IV, but could be detected through the full thickness of the cortex. Subsequent processing for cytochrome oxidase (CO) showed that the light columns in wet sections viewed under darkfield illumination matched the ocular dominance columns serving the enucleated eye. These columns labeled preferentially with an antibody to myelin basic protein, suggesting that greater myelin content accounted for their brighter appearance. However, when sections were counterstained with luxol fast blue, Gallyas and Woelcke myelin techniques, the enucleated eye's columns appeared pale. It is unclear why classical myelin stains and myelin basic protein immunohistochemistry yielded opposite results. Discrepant patterns of myelin distribution were also found in normal animals using different myelin stains. Luxol fast blue showed homogeneous staining in layer IVc of macaque striate cortex, but the Gallyas stain revealed a pattern of thin pale bands alternating with wide dark bands, matching the pattern seen with the Liesegang stain. The CO patches in layers II and III fit in register with the wide dark myelin bands. In layers II and III of striate cortex, the Gallyas and luxol fast blue methods both labeled the CO patches. However, in squirrel monkey V2 the Gallyas stain labeled the pale CO stripes, whereas luxol fast blue labeled the dark CO stripes. These results indicate that pattern of myelin staining in visual cortex can vary according to the choice of technique, and may not reflect the true distribution of myelin. Studies of myeloarchitecture should employ a variety of myelin techniques, including examination of unstained sections, to obtain the most accurate picture of cortical myelin content.

Animals↗
PubMed1996

Intrinsic variability of ocular dominance column periodicity in normal macaque monkeys.

Little is known about intrinsic variation from animal to animal in the periodicity of columnar systems within various regions of the mammalian cerebral cortex. To address this issue, complete mosaics of the ocular dominance columns were reconstructed from flat-mounts of the left and right striate cortex (V1) in six normal adult macaques (Macaca fascicularis). To identify the columns, we enucleated the right eye and subsequently processed striate cortex for cytochrome oxidase (CO) activity. Average column areas for the intact eye and the missing eye were nearly equal, confirming that monocular enucleation in adult macaques produces negligible column shrinkage. The contralateral eye's columns occupied more territory than the ipsilateral eye's columns, even in the central visual field representation (0 degree to 8 degrees), where they predominated by 52 to 48%. The column mosaics showed remarkable variation in periodicity. The number of column pairs along the V1/V2 border ranged from 101 sets in one monkey to 154 sets in another. Average column width along the V1/V2 border ranged between 670 and 395 microns, a nearly twofold difference. The widest columns were found in the foveal representation. This high degree of innate variability should be taken into account when considering the effects of various sensory manipulations (e.g., strabismus, anisometropia), which have been reported to alter the periodicity of ocular dominance columns. We found pronounced intrinsic variation in the width and number of ocular dominance columns in a sample of six M. fascicularis, indicating that the number of hypercolumns within a given cortical area can range widely among normal members of the same species.

Age Factors↗
PubMed1996

Anatomical demonstration of ocular dominance columns in striate cortex of the squirrel monkey.

The squirrel monkey is the only primate reported to lack ocular dominance columns. Nothing anomalous about the visual capacity of squirrel monkeys has been found to explain their missing columns, leading to the suggestion that ocular dominance columns might be "an epiphenomenon, not serving any purpose" (Livingstone et al., 1995). Puzzled by the apparent lack of ocular dominance columns in squirrel monkeys, we made eye injections with transneuronal tracers in four normal squirrel monkeys. An irregular mosaic of columns, averaging 225 microns in width, was found throughout striate cortex. They were double-labeled by placing wheat germ agglutinin-horseradish peroxidase into the left eye and [3H]proline into the right eye. The tracers labeled opposite sets of interdigitating columns, proving they represent ocular dominance columns. The columns were much clearer in layer IVc alpha (magno-receiving) than IVc beta (parvo-receiving). In the lateral geniculate body, the parvo laminae showed extensive mixing of ocular inputs, suggesting that increased label spillover contributes to the blurred columns in layer IVc beta. The cytochrome oxidase (CO) patches were organized into distinct rows, but they bore no consistent relationship to the ocular dominance columns. These experiments indicate that ocular dominance columns are less well segregated in squirrel monkeys than macaques, but they are present. This fact is pertinent to a recent study reporting that ocular dominance columns are absent in normal squirrel monkeys, but induced to form by strabismus (Livingstone, 1996).

Animals↗
PubMed1996

An adult-like pattern of ocular dominance columns in striate cortex of newborn monkeys prior to visual experience.

In macaque monkeys, the geniculocortical afferents serving each eye segregate in layer IVc of striate cortex during early life into a pattern of alternating inputs called ocular dominance columns. It has been disputed whether visual experience is necessary for the formation of ocular dominance columns. To settle this issue, fetal monkeys were delivered prematurely by Caesarean section at embryonic day 157 (E157), 8 d before the end of normal gestation. To avoid light exposure, the Caesarean section and all subsequent feedings and procedures were done in absolute darkness, using infrared night-vision goggles. Tritiated proline was injected into the right eye 1 d after delivery (E158). One week later at postnatal age 0 (P0), the equivalent of a full-term pregnancy (E165/P0), alternate sections of unfolded and flattened visual cortex were prepared for autoradiography or cytochrome oxidase (CO). All three newborns studied at E165/P0 had well segregated ocular dominance columns organized into the characteristic mosaic present in adults. In the upper layers, a mature pattern of CO patches (also known as blobs or puffs) was visible, aligned with the ocular dominance columns in layer IVc. Every other row of patches in layers II, III was labeled by [3H]proline. In V2, a distinct system of alternating thick-pale-thin-pale CO stripes was present. These findings indicate that stimulation of the retina by light is not necessary for the development of columnar systems in the visual cortex. Ocular dominance columns, patches, and V2 stripes all are well formed before visual experience. Even the thalamic input to the patches in the upper layers of striate cortex is segregated by eye in newborns.

Aging↗
PubMed1994

Glial domains and axonal reordering in the chiasmatic region of the developing ferret.

This study has examined the developing glial architecture of the optic pathway and has related this to the changing organization of the constituent axons. Immunocytochemistry was used to reveal the distribution of glial profiles, and DiI was used to label either radial glial profiles or optic axons. Electron microscopy was used to determine the distribution of glial profiles, axons, growth cones, and wrists at different locations along the pathway. Three different glial boundaries were defined: Two of these are revealed as changes in the distribution of vimentin-immunoreactive profiles occurring in the prechiasmatic optic nerve and at the threshold of the optic tract, respectively, and one by the presence of glial fibrillary acidic protein (GFAP)-immunoreactive profiles at the chiasmatic midline. The latter, midline boundary may be related to the segregation of nasal from temporal optic axons. The boundary at the threshold of the optic tract coincides with the segregation of dorsal from ventral optic axons that emerges at this location in the pathway. The segregation of old from young optic axons is shown to occur only gradually along the pathway. Glial profiles are most frequent in the deeper parts of the tract, coursing parallel to the optic axons and orthogonal to their usual radial axis. These are suggested to arise from later-growing radial glial fibers that are diverted to grow amongst the older optic axons. Those glial profiles may subsequently impede axonal invasion, thus creating the chronotopic reordering by forcing the later-arriving axons to accumulate superficially.

Animals↗
PubMed1991

Hb Geelong [beta 139(H17)Asn----Asp].

Hb Geelong [beta 139(H17)Asn----Asp] was detected in a German woman of Polish-Russian descent. It is an unstable variant which appears to increase the severity of a beta (+)-thalassemic phenotype in the propositus. The electrophoretic properties of Hb A and Hb Geelong are similar on cellulose acetate in both acidic and alkaline conditioning. The electrophoretic mobility and the amino acid analysis of beta XT-14 indicated the substitution Asn----Asp at beta 139. The sequence of beta XT-14 was confirmed by dansyl-Edman degradation. The slight increase observed in the P50 of whole blood is not intrinsic to the beta 139 substitution, but is thought to result from an increased 2,3-diphosphoglycerate level in response to anemia. No family studies were possible to investigate the mode of inheritance of either beta (+)-thalassemia or Hb Geelong in the propositus. Synthetic globin chain ratios suggest that impaired synthesis of the variant globin chain is partially responsible for the low level of Hb Geelong in peripheral blood.

2,3-Diphosphoglycerate↗
PubMed1986

(delta beta) zero thalassemia of the Southern Italian type. Its geographical origin and interaction with the sickle cell gene.

Hematological phenotypes and molecular defects were compared in 11 examples of heterozygous (delta beta) zero thalassemia. Despite differences in ethnic origins all cases had the gene deletion that is found in (delta beta) zero thalassemia of the Southern Italian type. HbF levels in these patients ranged from 3.6-14.6% with a mean +/- 1 SD of 8.9 +/- 3.1%. Variability in HbF output would suggest that additional factor(s) apart from deletions within the beta globin complex are involved in regulation of gamma gene expression. One individual, a compound-heterozygote for (delta beta) zero thalassemia and HbS, presented with a sickling disorder. Reduced HbF production in family members who are heterozygotes for (delta beta) zero thalassemia may explain the clinical picture in this instance.

Adult↗
PubMed1980

Platelet cryopreservation: a simple routine.

Cryopreservation of platelets as a blood-bank routine procedure offers functional platelets on demand. A simple method of freezing, thawing, and administering platelets which is within reach of any hospital with routine blood-banking facilities is outlined. Sixteen frozen-thawed platelet transfusions are reported.

Blood Platelets↗