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R L Faull

Publications and source records attributed to R L Faull.

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The organization and collateralization of corticostriate neurones in the motor and sensory cortex of the rat brain.

The organization and collateralization of corticostriate neurones in the motor and sensory cortex of the rat brain was investigated using double retrograde labelling techniques. The results demonstrated that the motor and sensory corticostriate projections are strongly bilateral with an ipsilateral predominance. The labelled corticostriate cells were medium-sized pyramidal cells localized predominantly in lamina Va, with fewer cells in lamina Vb and only the occasional cell in laminae III and VI. A significant proportion (13%) of corticostriate neurones in the sensory-motor cortex of the rat were double-labelled, indicating that they provide collateral projections to the striatum on both sides of the brain. The highest percentage of double-labelled corticostriate neurones was found in the primary motor cortex (14%) with lower percentages in the primary sensory cortex (10%) and in the forelimb and hindlimb sensory-motor overlap areas (6%).

Animals↗

Benzodiazepine receptors in the human cerebellar cortex: a quantitative autoradiographic and pharmacological study demonstrating the predominance of type I receptors.

The anatomical localization of benzodiazepine receptors in the human cerebellar cortex was studied using quantitative autoradiography following in vitro labelling of cryostat sections with [3H]flunitrazepam ([3H]FNZ), and the pharmacology of these receptors has been characterized by computerized, non-linear least squares regression analysis of [3H]FNZ displacement by FNZ, CL218,872 and ethyl beta-carboline-3-carboxylate (ECC) binding to membranes. The autoradiograms demonstrated that benzodiazepine receptors were present throughout all layers of the human cerebellar cortex; high concentrations of receptors were present in the molecular layer, moderate concentrations were present in the granular layer and a much lower density of receptors was seen in the intervening Purkinje cell layer. The pharmacological studies indicated that the human cerebellar cortex contained a high concentration of homogeneous benzodiazepine receptors which have high affinity for FNZ, ECC and CL218,872, i.e. type I sites.

Adult↗

The distribution and morphology of identified thalamocortical projection neurons and glial cells with reference to the question of interneurons in the ventrolateral nucleus of the rat thalamus.

The distribution and morphology of thalamocortical projection neurons and glial cells in the ventrolateral nucleus of the rat thalamus have been investigated using light and electron microscopic techniques. In this material thalamocortical projection neurons in the ventrolateral nucleus were identified by the retrograde transport of horseradish peroxidase following the placement of multiple injections of horseradish peroxidase in the primary motor and sensorimotor overlap regions of the cerebral cortex. The location of horseradish peroxidase-labelled thalamocortical projection neurons varied with the locus of injection in the motor and sensorimotor overlap cortex; caudal injections labelled cells in the rostrolateral region of the ventrolateral nucleus while injections involving successively more rostral regions of the cortex labelled cells in more medial and caudal regions of the nucleus. Labelled thalamocortical neurons were grouped in clusters with neuron pairs often closely applied to each other via non-synaptic junctional complexes. Where the field of labelled neurons was analysed in series of 1-micron-thick sections with phase contrast light microscopy, all neurons in the field were found to be clearly labelled with horseradish peroxidase. Thalamocortical neurons comprised mainly medium-to-large, multipolar ovoid-shaped cells which showed a large centrally placed nucleus with deep invaginations of the nuclear membrane. Two types of glial cells were identified: astrocytes, identified by their characteristic pale-staining ovoid nucleus, showed a close relationship to blood vessels, synaptic complexes and neurons; oligodendrocytes, distinguished by their darkly stained nucleus and cytoplasm, were somewhat smaller and showed a close association with myelinated fibres. These findings show that the rat ventrolateral nucleus comprises a homogeneous population of thalamocortical projection neurons and thus provide indirect evidence suggesting the absence of interneurons in the ventrolateral nucleus of the rat thalamus.

Animals↗

Opiate receptors in the human spinal cord: a detailed anatomical study comparing the autoradiographic localization of [3H]diprenorphine binding sites with the laminar pattern of substance P, myelin and nissl staining.

The anatomical localization of opiate receptors in the human spinal cord has been examined in six cases aged 7-41 years using quantitative autoradiographic methods following the incubation of fresh, unfixed cryostat sections with [3H]diprenorphine. In order to precisely localize the distribution of receptors in the spinal cord, the laminar anatomy of the spinal grey was demonstrated at each spinal level examined using 50-microns sections stained for myelin, Nissl substance and substance P. In all cases, autoradiograms demonstrated that opiate receptors were distributed in a similar fashion in the grey matter of the cervical, thoracic, lumbar, sacral and coccygeal regions of the human spinal cord. At all 25 spinal levels examined, opiate receptors were mainly localized within the upper laminae of the dorsal horn (laminae I-III) and within the tract of Lissauer. The highest density of opiate receptors was localized within the inner segment of lamina II where the receptors formed a very dense band lying immediately dorsal to lamina III. The density of receptors in this inner region of lamina II (33 +/- 2 fmol/mg) was more than two-and-one-half times greater than that in the remaining upper laminae which showed moderate receptor densities: lamina I (12 +/- 4 fmol/mg) and outer lamina II (13 +/- 3 fmol/mg) both showed similar receptor densities which were higher than those in lamina III (10 +/- 3 fmol/mg) The tract of Lissauer (11 +/- 2 fmol/mg) also showed a moderate density of opiate receptors which was intermediate between the densities in laminae I/IIo and the density of lamina III. The density of receptors in the remaining laminae of the spinal cord varied from moderately low to virtually zero. Moderately low densities of receptors were found in laminae V, VI, VIII, IX and X with very low levels within laminae IV and VII. In particular, in lamina VII opiate receptors were unable to be detected above normal background levels in the dorsal nucleus of Clarke. These results show that, as in other mammalian species, opiate receptors in the human spinal cord are mainly concentrated in the upper laminae of the dorsal horn and in the tract of Lissauer. The possible role of these receptors in modulating spinal nociceptive information is discussed with respect to previous findings on the relationship of opiate receptors to primary afferent fibres in the spinal cord.

Adolescent↗

Heterogeneous distribution of benzodiazepine receptors in the human striatum: a quantitative autoradiographic study comparing the pattern of receptor labelling with the distribution of acetylcholinesterase staining.

The distribution of benzodiazepine receptors in the human striatum was studied by quantitative autoradiography following in vitro labelling of cryostat sections with [3H]flunitrazepam, and the pattern of receptor-labelling was compared to the distribution of acetylcholinesterase (AChE) staining in adjacent sections. A heterogeneous pattern of benzodiazepine receptors was found in all regions of the striatum. The highest densities of receptors were seen in the ventral striatum (nucleus accumbens and olfactory tubercle), where very dense receptor patches aligned with both AChE-poor and AChE-rich regions. The dorsal striatum (caudate nucleus and putamen) contained lower concentrations of benzodiazepine receptors, but dense receptor patches were still evident (especially in the caudate nucleus) and these aligned with AChE-poor striosomes.

Acetylcholinesterase↗

Benzodiazepine receptors in the human spinal cord: a detailed anatomical and pharmacological study.

The anatomical distribution and pharmacological characteristics of benzodiazepine receptors in the human spinal cord were examined in four cases aged 20-41 years using in vitro autoradiography and biochemical assays of [3H]flunitrazepam binding. In all cases, the autoradiograms demonstrated that benzodiazepine receptors were distributed in a consistently similar fashion in the gray matter of the cervical, thoracic, lumbar and sacral regions of the human spinal cord. At all levels, the highest densities of benzodiazepine receptors were found to be localized within lamina II of the dorsal horn as defined on cytoarchitectonic, myeloarchitectonic and substance P immunocytochemical criteria. Within this lamina the receptors were concentrated mainly in its deeper, inner portion which lies immediately adjacent to lamina III, with some overlap dorsally into the outer segment of lamina II and ventrally into the adjacent region of lamina III. The lowest density of receptors was found in regions of laminae I, IV, VII and X; in particular, in lamina VII the lowest concentration of receptors was found in the dorsal nucleus of Clarke and the sacral parasympathetic nucleus. The remaining laminae of the spinal gray (laminae, V, VI, VIII and IX) showed a moderate density of receptors. Biochemical assays of membranes prepared from the lumbosacral cord indicated that these [3H]flunitrazepam binding sites have high affinity and have the pharmacological characteristics of the "central" Type II benzodiazepine receptor. These results show a high concentration of Type II benzodiazepine receptors in the substantia gelatinosa of the human spinal cord and suggest a possible role for these receptors in spinal sensory functions.

Adult↗

The visual cortico-striato-nigral pathway in the rat.

The organization of the visual cortico-striato-nigral pathway in the rat has been investigated in two sets of experiments using anterograde autoradiographic tracing techniques. First, in one group of animals, injections of tritiated amino acids were placed throughout the visual cortex to demonstrate the visual corticostriatal pathway. The results indicate that visual corticostriatal fibres terminate in a distinctive clustered pattern throughout the entire length of the ipsilateral dorsomedial striatum. The projection shows a longitudinal topographic organization with cortical loci projecting onto narrow longitudinal regions of the dorsomedial striatum. In addition to the ipsilateral projection, a substantially smaller contralateral visual corticostriatal projection was also demonstrated. In the second set of experiments, the visual corticorecipient region of the striatum demonstrated in the first set of experiments was injected with tritiated amino acids to demonstrate the "visual" striatonigral projection. The results indicate that striatonigral fibres from the dorsomedial striatum project throughout the rostrocaudal extent of the ventral region of the pars reticulata. As with the visual corticostriatal pathway, the projection shows a longitudinal topographic organization with striatal loci projecting onto longitudinal regions of the ventral pars reticulata; the most rostral regions of the dorsal striatum project to the most medial regions of the ventral pars reticulata and, likewise, successively more caudal regions of the dorsal striatum project to successively more lateral regions of the ventral pars reticulata. In addition to the main projection to the ventral pars reticulata, a second smaller component of the striatonigral pathway was traced to adjacent regions of the dorsal pars reticulata and ventral pars compacta. These findings provide evidence of a visual cortico-striato-nigral pathway to both the pars reticulata and pars compacta in the rat. It is suggested that the major projection onto the ventral pars reticulata may provide an input onto nigrotectal neurons and thereby complete an indirect visual corticotectal connection mediated via links in the basal ganglia.

Animals↗

Muscarinic cholinergic receptors in the human spinal cord: differential localization of [3H]pirenzepine and [3H]quinuclidinylbenzilate binding sites.

The localization of muscarinic cholinergic receptor subtypes was studied in the human spinal cord using in vitro labelling of cryostat sections with [3H]quinuclidinylbenzilate (QNB) and [3H]pirenzepine (PZ) followed by autoradiography. The highest densities of [3H]QNB binding were localized in laminae II (substantia gelatinosa) and IX (motor neurons); in contrast, the highest density of [3H]PZ binding was localized to lamina II where the binding density was 22-32% higher than in lamina IX. These results suggest that the M1 and M2 muscarinic cholinergic receptor subtypes may be differentially localized in sensory and motor regions of the human spinal cord.

Benzodiazepinones↗

The striatonigral projection and nigrotectal neurons in the rat. A correlated light and electron microscopic study demonstrating a monosynaptic striatal input to identified nigrotectal neurons using a combined degeneration and horseradish peroxidase procedure.

In a light and electron microscopic study of the substantia nigra of the rat, the distribution and morphology of nigrotectal neurons and the pattern of termination of striatonigral fibres have been examined following the placement of horseradish peroxidase injections in the superior colliculus and kainic acid lesions in the dorsal striatum. In confirmation of previous findings, nigrotectal neurons which had been identified by the retrograde transport of horseradish peroxidase from the superior colliculus had mainly medium sized somata, varied from fusiform to stellate in shape and were found in mainly ventral regions of the rostral two-thirds of the substantia nigra pars reticulata. On electron microscopic examination, single and multiple (from two to six) degenerating striatonigral boutons were found in synaptic contact with the soma, proximal mainstem dendrites and small dendrites (but mainly on small dendrites) of labelled nigrotectal and unlabelled nigral neurons in the ventral region of the pars reticulata. In addition, a small number of degenerating striatonigral boutons formed axoaxonic synapses with degenerating or normal boutons which were presynaptic to nigral dendrites. Almost all of the identified striatonigral synapses were of the symmetrical type, although a few degenerating boutons established asymmetrical synaptic contacts on unlabelled dendrites. These findings provide evidence of a monosynaptic input from the dorsal striatum to nigrotectal projection neurons in the substantia nigra and thus demonstrate the existence of a bineuronal pathway from the striatum through the substantia nigra to the superior colliculus. The possible significance of the pattern of termination of striatonigral fibres in the substantia nigra is discussed with reference to the known dendritic arborization of nigral neurons.

Animals↗

A comparative study of the neurons of origin of the spinocerebellar afferents in the rat, cat and squirrel monkey based on the retrograde transport of horseradish peroxidase.

The cell bodies of the neurons of the spinocerebellar pathways were examined using large injections of horseradish peroxidose into the cerebellum. Sections of each spinal segment were examined with both the DAB and the de Olmos O-dianisidine techniques. Results common to all three species were found. In Clarke's nucleus, the central cervical nucleus, and the spinal border cells there were many heavily labeled cells. Clarke's nucleus was found to project primarily ipsilaterally; the spinal border cells primarily contralaterally; and the central cervical nucleus bilaterally. In addition to these aggregates of spinocerebellar neurons there were numerous labeled neurons scattered throughout the spinal grey. Labeled neurons were found in all portions of the spinal grey except the substantia gelatinosa and lateral cervical nucleus and occurred in all spinal segments. They varied in morphology from large multipolar neurons, found predominantly in the ventral horn to small globular and fusiform neurons that were most abundant in the dorsal horn. These cells were found to project both ipsilaterally and contralaterally. Results common to only two of the species examined were also found. In the dquirrel monkey and the cat, but not the rat, the marginal layer of the dorsal horn in all segments of the spinal contained numerous labeled neurons. These marginal neurons were especially numerous in the squirrel monkey, where as many as 13 to 16 labeled neurons per section of the dorsal horn were found. In the rat and the squirrel monkey but not the cat, some intensely labeled large multipolar neurons were found in the sacral and caudal segments. These are the cells of Stilling's nucleus, a column of cells similar in position and orientation to that of Clarke's column but different in its projections and details of cytoarchitecture. Thus we have not only confirmed that Clarke's nucleus, the central cervical nucleus, and the spinal border cells project to the cerebellum but we have also found several new sources of spinocerebellar afferents.

Animals↗

The cerebellofugal projections in the brachium conjunctivum of the rat. II. The ipsilateral and contralateral descending pathways.

The cerebellofugal projections in the ipsilateral and contralateral descending pathways of the brachium conjunctivum (B.C.) in the rat have been investigated in 22 animals using the Fink-Heimer technique to demonstrate the axonal degeneration resulting from complete B.C. lesions (6), partial B.C. lesions (14) and control lesions dorsal to the B.C. (2). The incidental degeneration resulting from the concomitant involvement of the structures surrounding the B.C. is accounted for in terms of known fiber pathways and from the results in the control experiments. This study confirms Ramón y Cajal's ('03) original observation that cerebellofugal fibers in the B.C. project caudally throughout the length of the hindbrain via both ipsilateral and contralateral descending pathways. The fibers forming the ipsilateral descending pathway proceed ventrally from the B.C. at the level of the trigeminal motor nucleus, turn caudally and terminate within nucleus reticularis parvocellularis (Rpa). In particular, fibers within this pathway terminate densely in two cytoarchitecturally distinct Rpa subnuclei--nucleus "k" (Meessen and Olszewski, '49) and a caudal linear subnucleus--which project to the cerebellum (Faull, '77). The contralateral descending pathway (B.C.de) roceeds caudally from the decussation of the B.C. within the ventromedial region of the magnocellular nuclei of the reticular formation of the pons and medulla. Cerebellofugal fibers of the B.C.de terminate in a distinctive pattern within precerebellar brainstem nuclei: densely throughout the middle third of nucleus reticularis tegmenti pontis; in a longitudinal zone of each of the three pontine gray subnuclei; in the principal and dorsal accessory nuclei of the inferior olive; and sparsely within nucleus reticularis paramedianus. Fibers in the B.C.de also terminate within the magnocellular nuclei of the reticular formation, principally the nuclei reticularis pontis oralis and caudalis.

Animals↗

Apoptosis, neurotrophic factors and neurodegeneration.

Apoptosis is an active process of cell death characterized by distinct morphological features, and is often the end result of a genetic programme of events, i.e. programmed cell death (PCD). There is growing evidence supporting a role for apoptosis in some neurodegenerative diseases. This conclusion is based on DNA fragmentation studies and findings of increased levels of pro-apoptotic genes in human brain and in in vivo and in vitro model systems. Additionally, there is some evidence for a loss of neurotrophin support in neurodegenerative diseases. In Alzheimer's disease, in particular, there is strong evidence from human brain studies, transgenic models and in vitro models to suggest that the mode of nerve cell death is apoptotic. In this review we describe the evidence implicating apoptosis in neurodegenerative diseases with a particular emphasis on Alzheimer's disease.

Alzheimer Disease↗