Helen E. Pearson

Transneuronal degeneration of beta retinal ganglion cells in the cat.

Transneuronal retrograde degeneration of retinal ganglion cells was investigated following neonatal visual cortex ablation in the cat. After a survival time of at least 18 months, retinal ganglion cells projecting to the thalamus were labelled by retrograde transport of horseradish peroxidase. Filled ganglion cells were classified into α, β and γ types on the basis of dendritic morphology. In normal cats, α cells made up 8-10% of the total population in the sample area, β cells made up 64-67% and γ cells made up 23-27%. In retinae of visual cortex-ablated cats, normal numbers of α and γ cells were present, but the β cell population was depleted by 90% of normal. Thalamic projections of surviving retinal ganglion cells were investigated by anterograde transport of tritiated proline injected into the eye. In these animals, ablation of visual cortex resulted in almost complete degeneration of laminae A and A1 of the dorsal lateral geniculate nucleus. In the radioautographic material, projections from the retina to the degenerated parts of laminae A and A1 were barely detectable. Survival of some ganglion cell populations and death of others after neonatal visual cortex ablation may be explained in terms of the pattern of projections of the different cell types. We conclude that the majority of β cells degenerate following visual cortex ablation because of removal of cells in the dorsal lateral geniculate nucleus which form their sole or principal target. Alpha and γ cells and 10% of β-cells survive because of extensive collateral projections to targets other than cells of the laminae A and A1 of dorsal lateral geniculate nucleus.

Microglial invasion and activation in response to naturally occurring neuronal degeneration in the ganglion cell layer of the postnatal cat retina

Retinae of kittens between postnatal (P) days 2 and 10 were examined for the presence of degenerating neuronal profiles, normal nucleoli and microglia. Comparison of the numbers of degenerating profiles with numbers of axons lost from the optic nerve suggest that the majority of these profiles result from the degeneration of retinal ganglion cells. Analysis of local densities of the different profiles revealed different rates of cell loss, occurring at different times in central and peripheral retina. The period of rapid cell loss occurred between P2 and P3 in central retina compared to between P8 and P10 in peripheral retina. At both locations, these periods of rapid cell loss were accompanied by a decrease in the ratio of microglia to dying cells even though the absolute densities of microglia increased. However, calculation of the clearance times of cellular debris indicate that the speed of removal of degeneration products is greater during rapid cell loss, which suggests that cellular degeneration serves to activate the phagocytic process.

Retinal ganglion cell degeneration following loss of postsynaptic target neurons in the dorsal lateral geniculate nucleus of the adult cat

Kainic acid was used to produce selective degeneration of neurons in the dorsal lateral geniculate nucleus of the adult cat. This degeneration mimics the rapid loss of geniculate neurons seen after visual cortex ablation in the neonate. Following survivals of 2, 4, or 6 months, the geniculate was injected with horseradish peroxidase and the retinae were examined for the presence of retrogradely labeled cells. Analysis of ganglion cell density in peripheral nasal retina revealed a 58% loss of cells overall at 6 months. The proportion of cells labeled with horseradish peroxidase decreased more rapidly, until none were labeled at 6 months. Separate analysis of small, medium, and large ganglion cell populations revealed that only medium-sized cells were lost at 2 months whereas both medium and large cells were lost at 4 and 6 months. By 6 months, 92% of medium cells and 65% of large cells had degenerated. These results show that mature retinal ganglion cells in the cat maintain a dependence on target integrity for their continued survival. When the appropriate target is lost, the ganglion cells respond first by axon terminal retraction and then by cell death.

Atrophy and degeneration of ganglion cells in central retina following loss of postsynaptic target neurons in the dorsal lateral geniculate nucleus of the adult cat.

Selective degeneration of neurons in the dorsal lateral geniculate nucleus (dLGN) of the adult cat was produced by in situ injection of kainic acid. This rapid degeneration mimics the loss of lateral geniculate neurons seen after neonatal visual cortex ablation. Following survivals of 2, 4, or 6 months, the geniculate was injected with horseradish peroxidase (HRP) and the retinas were examined for the presence of retrogradely labeled, as well as unlabeled, cells. Total ganglion cell density in central nasal retina was not different from that of controls at 2 or 4 months, but by 6 months had decreased to 68% of control values. The proportion of cells labeled with HRP did not change at 2 months, but decreased from 84% in controls to less than 1% by 4 months, and none were labeled at 6 months. Surviving ganglion cells in central retina showed atrophy of the cell body, a finding not apparent in data from the retinal periphery. Shrinkage occurred in the few cells labeled with HRP surviving at 4 months, as well as among the unlabeled cells surviving at 4 and 6 months. These results show that the survival of central retinal ganglion cells in the cat continues to depend on intact target neurons beyond the period of development. Mature ganglion cells in central retina respond to loss of appropriate targets first by axon terminal retraction and then by atrophy and cell death. However, when compared to the response of cells located in far peripheral retina following dLGN neuron loss, central ganglion cells take longer to undergo axonal retraction and a greater proportion of the central ganglion cells, although atrophied, survive after 6 months.

Neocortical connections in fetal cats

The major extrinsic projections to and from visual and auditory areas of cerebral cortex were examined in fetal cats between 46 and 60 days of gestation (E46-E60) using axonal transport of horseradish peroxidase either alone or in combination with tritiated proline. Projections to visual cortex from the dorsal lateral geniculate nucleus and lateral-posterior/pulvinar complex exist by E46, and those from the contralateral hemisphere, claustrum, putamen, and central lateral nucleus of the thalamus are present by E54-E56. In addition, cells in the medial geniculate nucleus project to auditory cortex by E55. At E54-E56 efferent cortical projections reach the contralateral hemisphere, claustrum, putamen, lateral-posterior/pulvinar complex and reticular nucleus of the thalamus. Cells in visual cortex also project to the dorsal and ventral lateral geniculate nuclei, pretectum, superior colliculus and pontine nuclei, and cells in auditory cortex project to the medial geniculate nucleus. Except for interhemispheric projections, all pathways demonstrated are ipsilateral, and projections linking cerebral cortex with claustrum, dorsal lateral geniculate nucleus and lateral-posterior/pulvinar complex are reciprocal. The reciprocal projections formed with the dorsal lateral geniculate nucleus, lateral-posterior/pulvinar complex and the claustrum show a greater degree of topological organization compared to the projections formed with the contralateral hemisphere and superior colliculus, which show little or no topological order. Therefore, the results of the present study show that the major extrinsic projections of the cats visual and auditory cortical areas with subcortical structures are present by the eighth week of gestation, and that the origins and terminations of many of these projections are arranged topologically.

The effects of neonatal monocular enucleation on the organization of ipsilateral and contralateral retinothalamic projections in the rabbit

Autoradiographic methods were used to compare the ipsilateral and contralateral retinothalamic projections in pigmented Dutch-Belted rabbits that had neonatal monocular enucleation with the projections found in normally reared rabbits. In the normal adult rabbit, there is dense label throughout the dorsal lateral geniculate nucleus (LGd) except for a decreased label density in the region corresponding to the ipsilateral input. Following neonatal monocular enucleation, the contralateral projection fills in the part of the LGd corresponding to the ipsilateral input. Our data indicate that following monocular enucleation, two processes occur: an arrest of the segregation process and an expansion of the contralateral projection into the space normally containing the terminals of the ipsilateral projection. In addition, this filling in of the terminal space occurs relatively rapidly and is completed by day 14. No changes, however, were observed in the ipsilateral projection to the LGd. Unlike the LGd, the ventral lateral geniculate nucleus and the intergeniculate leaflet showed increases in the size of the ipsilateral projection region, and no changes in the contralateral projection. The present findings suggest that there may be different mechanisms governing whether alterations in the distribution of retinothalamic projections will occur in either the ipsilateral or contralateral nucleus.

Selectivity of kainic acid as a neurotoxin within the dorsal lateral geniculate nucleus of the cat: a model for transneuronal retrograde degeneration

SummaryIn situ injections of the cytotoxin kainic acid were used to make localized lesions of the dorsal lateral geniculate nucleus in the adult cat to produce a model for studying the effects of postsynaptic target loss. Kainic acid has been used extensively to produce lesions of neuronal cell bodies within the central nervous system. However, the selectivity of kainic acid has been questioned, as it may also affect afferent terminals or axons of passage. Retinal projections to degenerated geniculate nuclei were visualized 1 week after kainate injection using anterograde labelling with horseradish peroxidase and electron microscopy. The results demonstrate the presence of afferent terminals within regions of neuronal loss, and hence the selectivity of kainic acid for intrinsic geniculate neurons.

Gliosis and ganglion cell death in the developing cat retina during hydrocephalus and after decompression

Even after surgical decompression, infantile hydrocephalus often results in permanent neurological symptoms, including visual deficits. However, little is known about the cellular changes that may be responsible for these effects. The present study was designed to analyze the retinae of normal, mildly hydrocephalic, severely hydrocephalic and surgically decompressed kittens to determine if changes occur in the density and size of retinal ganglion cells. Hydrocephalus was induced in 10 day old kittens by intra-cisternal injection of kaolin. Kittens were allowed to survive from 7 to 28 days after injection. Animals that were decompressed received ventriculoperitoneal shunts 10-15 days after the induction of hydrocephalus and were sacrificed 10-14 days after shunt placement. The density and area of neuronal and glial cells were determined within a sample area in peripheral nasal retina. Total cell density was significantly increased in mildly and severely hydrocephalic animals but returned to normal following decompression. This change represents a significant increase in the glial population. In addition, there was a significant loss of ganglion cells in both the severely hydrocephalic and the shunted groups. Based on these findings, we conclude that gliosis occurs as a result of cell death in the retina following severe hydrocephalus, and decompression is unable to reverse these effects. Furthermore, gliosis occurs in mild cases of hydrocephalus, and may be an early indication that cellular degeneration will follow.

Dorsal Scapular Artery Variations and Relationship to the Brachial Plexus, and a Related Thoracic Outlet Syndrome Case

Rationale Knowledge of the relationship of the dorsal scapular artery (DSA) with the brachial plexus is limited. Objective We report a case of a variant DSA path, and revisit DSA origins and under-investigated relationship with the plexus in cadavers. Methods The DSA was examined in a male patient and 106 cadavers. Results In the case, we observed an unusual DSA compressing the lower plexus trunk, that resulted in intermittent radiating pain and paresthesia. In the cadavers, the DSA originated most commonly from the subclavian artery (71%), with 35% from the thyrocervical trunk. Nine sides of eight cadavers (seven females) had two DSA branches per side, with one branch from each origin. The most typical DSA path was a subclavian artery origin before passing between upper and middle brachial plexus trunks (40% of DSAs), versus between middle and lower trunks (23%), or inferior (4%) or superior to the plexus (1%). Following a thyrocervical trunk origin, the DSA passed most frequently superior to the plexus (23%), versus between middle and lower trunks (6%) or upper and middle trunks (4%). Bilateral symmetry in origin and path through the brachial plexus was observed in 13 of 35 females (37%) and 6 of 17 males (35%), with the most common bilateral finding of a subclavian artery origin and a path between upper and middle trunks (17%). Conclusion Variability in the relationship between DSA and trunks of the brachial plexus has surgical and clinical implications, such as diagnosis of thoracic outlet syndrome.

Role of comprehension on performance at higher levels of Bloom's taxonomy: Findings from assessments of healthcare professional students: Bloom's Taxonomy and Healthcare Professionals

The first four levels of Blooms taxonomy were used to create quiz questions designed to assess student learning of the gross anatomy, histology, and physiology of the gastrointestinal (GI) system. Information on GI histology and physiology was presented to separate samples of medical, dental, and podiatry students in computer based tutorials where the information from the two disciplines was presented either separately or in an integrated fashion. All students were taught GI gross anatomy prior to this study by course faculty as part of the required curriculum of their respective program. Student responses to the quiz questions were analyzed to assess both the validity of Blooms cumulative hierarchy and the effectiveness of an integrated curriculum. No statistically significant differences were found between quiz scores from students who received the integrated tutorial and from those who received the separate tutorials. Multiple regression analyses provided partial support for a cumulative hierarchy where scores on the lower levels of Blooms taxonomy predicted scores on higher levels. Notably, in the majority of regression analyses, the comprehension score was the key foundational predictor for application and analysis scores. This study supports the suggestion that educators increase the number of comprehension level questions, even at the expense of knowledge level questions, in course assessments both to evaluate lower order cognitive skills and also as a predictor of success on questions requiring application and analysis levels of the higher order cognitive skills of Blooms taxonomy. Anat Sci Educ 11: 433–444.