Biomedical subjects
A C Rosenquist
Publications and source records attributed to A C Rosenquist.
Ibotenic acid lesions in the pedunculopontine region result in recovery of visual orienting in the hemianopic cat.
Cats rendered hemianopic by a unilateral visual cortical ablation can recover the visual orienting response in the hemianopic visual field following disruption of the caudal non-tectotectal containing half of the commissure of the superior colliculus. Ibotenic acid lesions of a small 'critical zone' in the contralateral substantia nigra result in a similar recovery effect. A conceptual framework developed by Wallace et al. (1990) [J. Comp. Neurol. 296, 222-252] proposed that elimination of contralateral substantia nigra 'critical zone' inhibition on the superior colliculus ipsilateral to a visual cortical lesion is responsible for the recovery. This model is insufficient, however, to explain the observation that hemi-decorticate cats with contralateral substantia nigra 'critical zone' lesions which include but extend beyond the 'critical zone' do not demonstrate the recovery. In these cats, subsequent transection of the commissure of the superior colliculus does lead to the recovery. We hypothesize that another projection through the caudal commissure of the superior colliculus, from the pedunculopontine nucleus, is involved in the recovery effect. Visual orienting behavior was recorded before and after ibotenic acid lesions made in the pedunculopontine nucleus region contralateral to a visual cortical ablation in 16 cats. Four cats with lesions in a small rostral region of the contralateral pedunculopontine nucleus recovered the visual orienting response in the previously hemianopic visual field. Contralateral tectal projections from the pedunculopontine nucleus are thought to be cholinergic and terminate as distinct patches in the intermediate gray layers of the superior colliculus. Since this region of the pedunculopontine nucleus also receives GABA-ergic afferents from the substantia nigra, we propose that a subcortical neural circuit including the substantia nigra, pedunculopontine nucleus, and superior colliculus is involved in the recovery of visual orienting.
Disinhibition of the superior colliculus restores orienting to visual stimuli in the hemianopic field of the cat.
Following unilateral removal of all known visual cortical areas, a cat is rendered hemianopic in the contralateral visual field. Visual orientation can be restored to the blind hemifield by transection of the commissure of the superior colliculus or by destruction of the superior colliculus (SC) or the substantia nigra pars reticulata (SNpr) contralateral to the cortical lesion. It is hypothesized that a mechanism mediating recovery is disinhibition of the SC ipsilateral to the cortical lesion. The ipsilateral nigrotectal projection exerts a robust inhibitory tone onto cells in the SC. However, ibotenic acid destruction of SNpr neurons, which should decrease inhibition onto the SC, does not result in recovery. The failure of ipsilateral SNpr lesions to produce recovery puts into question the validity of SC disinhibition as a mechanism of recovery. We directly tested the disinhibition hypothesis by reversibly disinhibiting the SC ipsilateral to a visual cortical lesion with a gamma-aminobutyric acid (GABA)A antagonist, bicuculline methiodide. In accordance with the hypothesis, transient disinhibition of the SC restored visual orienting for several hours in three of eight animals. Recovery was not a volume or pH effect and was distinct from the release of irrepressible motor effects (i.e., approach and avoidance behaviors) seen within the first hour after injection. Thus, in the absence of all visual cortical areas unilaterally, disinhibition of the SC can transiently restore the ability of the cat to orient to visual stimuli in the previously "blind" hemifield.
Ibotenic acid lesions of the substantia nigra pars reticulata ipsilateral to a visual cortical lesion fail to restore visual orienting responses in the cat.
Unilateral removal of all known visual cortical areas in the cat renders the animal hemianopic in the contralateral visual field as measured by visual perimetry and other behavioral tests. We have shown that visual orientation behavior can be restored to the previously blind hemifield by destruction of a critical zone in the substantia nigra pars reticulata contralateral to a cortical lesion (Wallace et al., J. Comp. Neurol. 296:222-252, 1990). The model proposed to explain this recovery postulates that damage to the crossed nigrotectal projection disinhibits the superior colliculus ipsilateral to the cortical lesion and this leads to recovery. If disinhibition can account for recovery, then destruction of the uncrossed nigrotectal projection, which is known to exert a tonic inhibition on the superior colliculus, should also result in recovery. We made unilateral visual cortical ablations and ipsilateral ibotenic acid lesions of the substantia nigra pars reticulata. Visual orienting behavior was assessed in animals for a period of 4 to 31 weeks. Contrary to the prediction of the model, we failed to observe a recovery of visual orienting behavior in the blind hemifield in any of 23 animals.
Ibotenic acid lesions of the superior colliculus produce longer lasting deficits in visual orienting behavior than aspiration lesions in the cat.
We compared the effects of unilateral surgical aspiration and ibotenic acid produced lesions of the superior colliculus (SC) on visual orienting behavior in 20 cats. Four animals with aspiration lesions initially showed an hemianopia in the contralateral hemifield which recovered fully in 4.5 weeks or less. These lesions also destroyed axons in the commissure of the superior colliculus (CS). In 9 animals we produced complete loss of cells in one SC, with preservation of axons in the CSC, by injections of ibotenic acid. In these animals the contralateral hemianopia persisted for an average of 16.6 weeks, but may have persisted longer had we not intervened by either sacrificing the animal or ablating the visual cortex contralateral to the SC lesion. The cortical lesion produced an immediate hemianopia in the contralateral hemifield and a recovery in the previously hemianopic ('collicular') hemifield. In the remaining 7 animals with attempted ibotenic acid lesions, 5 had incomplete lesions and 2 others sustained major damage to the SC as well as the CSC. These 7 animals recovered visual orienting on an average of 3.0 weeks postoperatively. We conclude that unilateral loss of collicular cell function and the presence of fibers coursing through the commissure of the superior colliculus are both necessary for the prolonged deficit in visual orienting behavior. We suggest that competition between the two hemifields may play a role in the hemianopia caused by collicular manipulations and that the cholinergic pathway from the pedunculopontine nucleus to the contralateral SC via the CSC may be involved.
Clinicopathologic study of paraneoplastic brainstem encephalitis and ophthalmoparesis.
We report three patients who exhibited ophthalmoparesis as an early manifestation of progressive paraneoplastic brainstem encephalitis. In two patients, anti-Hu antibodies were detected, whereas in a third, found at postmortem to have thyroid cancer, no antibodies were identified. Postmortem examination of two patients disclosed extensive gliosis, perivascular inflammation, and cell loss in the midbrain and pontine tegmentum. In one of these patients, there was selective neuronal loss within the third, fourth, and sixth nerve nuclei. We conclude that supranuclear or nuclear ophthalmoparesis may be the initial manifestation of paraneoplastic brainstem encephalitis. Our pathologic data suggest that the ophthalmoparesis may result from selective neuronal death within the brainstem tegmentum and ocular motor nuclei.
The spatial relationship between the cerebral cortex and fiber trajectory through the corpus callosum of the cat.
We related fiber trajectory through the feline corpus callosum to the site of fiber origin in the cortical mantle and to functional modality. The cortical fields which contribute axons to the different portions of the corpus callosum were revealed by applying horseradish peroxidase (HRP) to the cut ends of selected groups of callosal axons in twelve adult cats. Overall, the application of HRP at progressively more caudal positions in the corpus callosum labels fields of neurons at successively more caudal positions in the cerebral cortex. Comparison of these data to functionally distinct cortical zones shows that the callosal body conveys a mixture of fibers arising from functionally diverse regions of the cerebrum, whereas portions of the rostral and caudal ends appear to be essentially unimodal, conveying motor and visual signals, respectively.
Dyke Award paper. MR of wallerian degeneration in the feline visual system: characterization by magnetization transfer rate with histopathologic correlation.
PURPOSE: To examine the utility of measuring magnetization transfer ratio for for delineating the dynamic changes of wallerian degeneration which occur after controlled injury in a feline model in which anatomic pathways are well understood. METHODS: Using standard neurosurgical techniques, discrete lesions were made to ablate the visual cortex. Gradient imaging was performed serially at 1.5 T, with and without a saturation pulse to create a magnetization transfer effect. At varying intervals, the animals were killed for histologic analysis. RESULTS: Within the first 2 weeks there is a statistically significant increase in magnetization transfer ratio relative to the control hemisphere within the white matter connections between the lateral geniculate nucleus and the visual cortex at a time when no effects are visually detectable on spin-echo images. Between 16 and 28 days, this reverses to a decrease in magnetization transfer ratio in both the lateral geniculate nucleus itself and the adjacent superolateral white matter. More remote white matter tracts remained stable, without significant change. CONCLUSIONS: Magnetization transfer ratio seems to be more sensitive for early detection of degeneration than conventional spin-echo imaging. Moreover, temporal changes in magnetization transfer ratio seem to correspond well with known histologic phases of wallerian degeneration.
Fragmentation of the Golgi apparatus of motor neurons in amyotrophic lateral sclerosis (ALS). Clinical studies in ALS of Guam and experimental studies in deafferented neurons and in beta,beta'-iminodipropionitrile axonopathy.
Previous morphological immunoenzymatic studies with organelle-specific antibodies have disclosed an apparent fragmentation of the Golgi apparatus in large numbers of motor neurons in 12 cases of sporadic, non-Guamanian amyotrophic lateral sclerosis (ALS) in three cases of other types of motor neuron disease and in one case of a mitochondrial myopathy with cytochrome c oxidase deficiency. Motor neurons with fragmented Golgi apparatus were moderately atrophic; in these cells, discrete immunostained elements of the organelle were twice as many as in normal neurons, and the size of each Golgi element and the percentage of the cytoplasmic area occupied by the Golgi apparatus were reduced (Am J Pathol 1992, 140: 731-737). In this report we have confirmed the fragmentation of the organelle of motor neurons in the spinal cord in six sporadic cases of Guamanian ALS. In four of the six cases the clinical course was 1 to 2 years. The percentages of motor neurons with fragmented Golgi apparatus varied from 38 to 92. Motor neurons from three additional cases of Guamanian ALS of clinical duration from 5 to 7 years did not show fragmentation of the Golgi apparatus. In two cases of Guamanian ALS and in one non-Guamanian ALS, all neurons with ubiquitin-positive skein-like or granular inclusions believed to be pathognomonic for ALS had fragmented Golgi apparatus. To examine whether the fragmentation of the Golgi apparatus results from reactions to either neuronal deafferentation or to lesions of proximal axons, we conducted two experimental studies. In the first study, we examined in cats the Golgi apparatus of deafferented neurons of the dorsal lateral geniculate nucleus. In the second study, we examined the Golgi apparatus of motor neurons in the spinal cord of rats with proximal axonopathy induced by beta,beta'-iminodipropionitrile. In these two experiments, the neuronal Golgi apparatus studied by immunoenzymatic techniques and morphometry, was not fragmented. Taken together, the results of these studies strongly suggest that the fragmentation of the Golgi apparatus of motor neurons in ALS represents an important and perhaps early change of the organelle that may be involved in the pathogenesis of ALS. The fragmentation of the Golgi apparatus of motor neurons is a fairly specific and easily recognizable marker of ALS and may be used together with other criteria for comparisons between the human disease and proposed animal models of the disorder.
Detection of early axonal degeneration in the mammalian central nervous system by magnetization transfer techniques in magnetic resonance imaging.
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Ibotenic acid lesions of the lateral substantia nigra restore visual orientation behavior in the hemianopic cat.
Transection of non-tectotectal fibers in the caudal one-half of the commissure of the superior colliculus restores visual orienting to a cat previously rendered hemianopic by a large unilateral visual cortical lesion. Other observations related to this recovery phenomenon (i.e., the Sprague effect) have suggested that the caudal commissural fibers whose destruction produces the recovery 1) are contralateral afferents to the superior colliculus on the side of the cortical lesion, and 2) profoundly influence visuo-motor processing in this superior colliculus. We performed anatomical and behavioral experiments to determine which of the more than 40 contralateral collicular afferents are directly involved in the Sprague effect. To guide subsequent behavioral studies, we performed a pilot anatomical experiment in which we injected WGA-HRP unilaterally into one superior colliculus at identical retinotopic loci in each of a pair of cats. One cat was normal (control), and the other (experimental) had previously received a caudal transection of the collicular commissure. Quantitative comparison of the retrograde labeling in collicular afferents revealed that a number of mesencephalic regions contain neurons that project to the colliculus via the caudal collicular commissure. Additional collicular injections of WGA-HRP demonstrated the exact location and distribution of collicular afferent neurons within these nuclei. In the behavioral experiments, we attempted to replicate the Sprague effect by destroying the neurons giving rise to the axons in the caudal collicular commissure. Ibotenic acid lesions of these neurons were performed in cats that were hemianopic following the removal of the contralateral visual cortex. Small lesions of a "critical zone" in the rostro-lateral substantia nigra pars reticulata and possibly the overlying ventral zona incerta consistently produced a visual recovery whereas lesions of the other collicular afferents did not. Paradoxically, large nigral lesions that also included the critical zone did not result in a recovery. A conceptual framework for these findings involving striato-nigro-tecto-preoculomotor interactions is presented.
Recovery from cortical blindness mediated by destruction of nontectotectal fibers in the commissure of the superior colliculus in the cat.
Transection of the commissure of the superior colliculus restores visual orientation behavior to a cat previously rendered hemianopic by a unilateral visual cortical lesion (the Sprague effect). Using two methods, we asked whether this recovery resulted from the severing of the tectotectal component of the commissure or whether the destruction of some other connection was responsible. First, we transected either the rostral or the caudal one-half of the tectal commissure in hemianopic cats. If destruction of tectotectal fibers is responsible for the Sprague effect, then only rostral transections should produce the recovery since nearly all tectotectal connections lie in the rostral one-half of the commissure. However, rostral cuts failed to produce a recovery, whereas caudal commisurotomies did. Second, ibotenic acid was used to destroy the cells in the superior colliculus contralateral to the cortical lesion. This lesion eliminated the contralateral tectotectal pathway from the contralateral colliculus but left other fibers (originating elsewhere but coursing through the commissure) largely intact. These ibotenic acid lesions failed to produce the recovery; but when the caudal portion of the tectal commissure was subsequently transected in the same animals, the recovery was observed. The results of both experiments support the conclusion that the transection of a nontectotectal component of the commissure of the superior colliculus is responsible for the recovery of visual orientation behavior in a cortically blind cat.
Efferent projections of the thalamic intralaminar nuclei in the cat.
Efferent projections of the central lateral (CL), paracentral (PC) and central medial (CE) intralaminar nuclei (ILN) to cortical and subcortical sites were studied in the cat. The combined methods of electrophysiologically guided cortical injections of tritiated leucine and stereotaxic injections of horseradish peroxidase (HRP) into the CL and PC nuclei were utilized. Additionally, fluorescent double-labeling techniques demonstrated patterns of intralaminar axon collateralization. We found that the ILN project ipsilaterally to all visual cortical areas except area 17. Projections to visual cortex are not arranged topographically or retinotopically. The ILN also project to the frontal eye fields (areas 6 and 8), anterior cingulate gyrus, suprasylvian fringe of the auditory cortex, insular cortex, parietal areas 5 and 7, caudate nucleus and claustrum. We noted especially heavy projections to the frontal eye fields and parietal areas 5 and 7. Fibers from the ILN terminate in cortical layers I and VI, and at the layer III-IV border. The demonstration of collateralization of ILN axons to two separate cortical areas implies that the same neuronal message may pass from the ILN to multiple cortical areas. It is concluded that the ILN may mediate a general cortical activation and may play a role in attention to visual, auditory and somatosensory (especially nociceptive) stimuli.
Afferent connections of the thalamic intralaminar nuclei in the cat.
Afferents to the central lateral (CL), paracentral (PC) and central medial (CE) intralaminar nuclei (ILN) from cortical and subcortical sites were studied in the cat. We utilized stereotaxically guided injections of HRP into the CL and PC nuclei and tritiated leucine injections into various visual, parietal and limbic areas of cortex to demonstrate these connections. In studying the relatively weak visual cortical projections to the ILN, we demonstrated projections from areas 19, 20a, 21a, 21b, AMLS, PMLS and PLLS. However, our HRP injections into the ILN often revealed only a few labeled cells in any of the above areas; therefore conclusions regarding the absence of projections to ILN from remaining visual cortical areas should be made cautiously. The ILN receive heavier projections from the frontal eye fields, cingulate cortex, splenial cortex, insular cortex, somatosensory areas SI and SII, auditory areas SF, AII, and Ep, and parietal areas 5 and 7. The most robust projections appear to be from from frontal eye fields, cingulate and parietal areas. No topography was apparent in the projections to the ILN. All cortical projections originate ipsilaterally from layers V and VI. Heavy subcortical projections to the ILN originate in the pretectum, superior colliculus, reticular formation, and periaqueductal grey. Fewer afferents arise from several other brainstem and thalamic nuclei.
Ischemic lesions of the occipital cortex and optic radiations: positron emission tomography.
We used 18-F-fluoro-2-deoxyglucose positron emission tomography (PET) and computed tomography (CT) to study eight patients with homonymous hemianopias or quadrantanopias due to ischemic lesions of the visual pathways. Four patients with ischemic damage to all or part of the occipital lobe had decreased glucose metabolism in the affected region. Three patients with ischemic damage limited to the optic radiations had decreased glucose metabolism in the portion of striate cortex appropriate for the visual field defect. Changes in glucose metabolism frequently occurred in the undamaged ipsilateral thalamus and visual association areas.
Corticocortical connections among visual areas in the cat.
The cortical interconnections of 17 visual areas in the cat were studied by making single injections through recording micropipettes of the neuroanatomical tracers 3H-leucine and horseradish peroxidase (HRP) into the visual cortex of 40 adult animals. Coronal sections from each of the brains were analyzed for location of silver grains and HRP-filled neurons. There are five main results: (1) all corticocortical connections among visual areas are reciprocal. (2) Each cortical visual area has a unique set of cortical connections; the cortical targets of no two cortical visual areas are identical. (3) There is a vast and complicated pattern of connections among the visual areas which implies that there are numerous parallel circuits which run through any one visual area. (4) The connections among the cortical visual areas link retinotopically similar loci and are consistent with the visuotopic maps which microelectrode recording experiments have provided. (5) The connections among visual cortical areas often originate from, or terminate in, discontinuous patches within each area; this result obtains not only for areas 17, 18, 19, and posteromedial lateral suprasylvian area (PMLS), but for at least 13 other areas as well. The data reveal many parallel pathways and suggest multiple functional circuits interconnecting visual cortical areas. Since each visual area has multiple inputs and outputs it may have multiple functions, a different one for each of the circuits of which it is a part.
Laminar origins of visual corticocortical connections in the cat.
The interconnections among visual areas in cat cortex were studied with respect to the specific laminae in which the cortically projecting neurons are located. Single injections of HRP were made through recording micropipettes into nine different visual areas. In 15 cortical areas the laminar distribution of neurons which were retrogradely filled with HRP was plotted. In this way we determined the laminar origins of the cortical projections to the nine separate cortical visual areas which were injected. There are three major observations. First, areas 17 and 18 are the only two visual areas in which layers II and III are the primary site of cortically projecting cells; in the other 13 areas the deeper layers of cortex provide a large percentage of such neurons. Second, within any one cortical area, cortically projecting neurons may be distributed among different layers; the specific layer depends upon the cortical target of those neurons. Third, any one cortical area receives projections from several different cortical layers, the specific layers being dependent upon the area from which the projection originates. An individual cortical area, therefore, contributes to several different cortical visual circuits, with each of these circuits defined by the laminar connections of its neurons.
The projections of single thalamic neurons onto multiple visual cortical areas in the cat.
Fluorescent dyes Fast Blue and Nuclear Yellow injected into pairs of visual cortical and parietal 'association' cortical areas in the cat revealed the presence of retrogradely double-labeled cells in the intralaminar nuclei and lateral posterior-pulvinar complex of the thalamus. These results demonstrate the projection of individual thalamic neurons onto multiple cortical areas.