The use of c-fos as a metabolic marker in neuronal pathway tracing.

The use of c-fos protein (Fos) immunocytochemistry as a metabolic marker for tracing neuroanatomical connections, seizure pathways and sites of action of neuroactive drugs is discussed in this report. Fos immunocytochemistry will be very useful for these purposes providing that a number of potential problems are recognized and controlled. These include the observations that Fos exists basally in neurons and can be non-specifically elevated after behavioural stress; neuronal bursting is required to elevate Fos in neurons in anaesthetized animals; drugs such as ketamine can block Fos elevation in neurons; the time-course of Fos induction and decay varies with different inducing stimuli and the brain region sampled; and some brain regions do not express Fos after any treatments tried so far.

Tubular expression of intercellular adhesion molecule-1 during renal allograft rejection.

Molecules responsible for adhesion between cells are known to play an important role in the immune response. The expression of one of these molecules, intercellular adhesion molecule-1 (ICAM-1), was examined on normal and allografted kidneys using a specific monoclonal antibody and an indirect immunoperoxidase technique. The expression of this molecule was compared to that of HLA class II antigens.

Long-term potentiation and the induction of c-fos mRNA and proteins in the dentate gyrus of unanesthetized rats.

We tested the hypothesis that the nuclear proto-oncogene c-fos is involved in long-term potentiation (LTP) of the perforant path-dentate gyrus synapse in awake freely moving rats. High-frequency stimulation that produced LTP induced c-fos mRNA and protein in the dentate granule cells but not in CA1, CA3, or the entorhinal cortex. However, the degree of LTP induction did not correlate with the degree of c-fos induction.

The neuroprotective actions of a calcium channel antagonist, flunarizine, in the infant rat.

One postulated final common pathway leading to neuronal death after hypoxic-ischemic insults is an increase in intracellular calcium concentrations. We examined the effect of pretreatment with flunarizine, a calcium channel antagonist known to pass the blood brain barrier, on the behavioral and histologic changes after an hypoxic-ischemic insult in the infant rat. The 21-d-old rats were subjected to unilateral carotid ligation, then to 2 h of hypoxia.

The distribution of neurotensin receptors and acetylcholinesterase in the human caudate nucleus: evidence for the existence of a third neurochemical compartment.

The distribution of neurotensin receptors in the human caudate nucleus was studied using autoradiographic methods following in vitro labelling of cryostat sections with [3H]neurotensin, and the pattern of receptor labelling was compared to the distribution of acetylcholinesterase (AChE) staining in adjacent sections. A heterogeneous pattern of neurotensin receptors was found in the caudate nucleus. Patches of low receptor density aligned with the AChE-poor striosomes, regions of moderate receptor density corresponded with the AChE-rich matrix zone, and annular regions of high receptor density aligned with the AChE-negative border zone lying between the AChE-poor striosome and the AChE-rich matrix compartments.

[3H]glycine binding sites, NMDA and PCP receptors have similar distributions in the human hippocampus: an autoradiographic study.

The distribution of [3H]glycine binding sites was compared with that of N-methyl-D-aspartate (NMDA) receptors labelled with L-[3H]glutamate, and with that of phencyclidine (PCP) receptors labelled with [3H]1-(1-(2-thienyl)-cyclohexyl)piperidine ([3H]TCP) in sections from 7 normal human hippocampi. The results indicate that strychnine-insensitive glycine binding sites are present in high concentrations in CA1 and the molecular layer of the dentate gyrus. This distribution is very similar to the distributions of NMDA and PCP receptors in the human hippocampus.

Immediate-early genes, kindling and long-term potentiation.

The mechanism(s) by which long-term changes are induced and maintained in the nervous system are poorly understood. Kindling is an example of a permanent change in brain function that results from repeated elicitation of seizures. Recently, a class of genes called "immediate-early genes" that were previously thought to be only involved in cell division, differentiation and perhaps neoplasia have been shown to be rapidly and transiently induced in adult neurons following afterdischarges, ECS and chemically-evoked seizures.

Excitatory amino acid receptors in the human cerebral cortex: a quantitative autoradiographic study comparing the distributions of [3H]TCP, [3H]glycine, L-[3H]glutamate, [3H]AMPA and [3H]kainic acid binding sites.

The excitatory amino acids are probably the major neurotransmitters in the cerebral cortex, and they act through at least three receptors: the N-methyl-D-aspartate, the quisqualate and the kainic acid receptors. Under the appropriate conditions, [3H]1-(1-(2-thienyl)-cyclohexyl)piperidine [( 3H]TCP), [3H]glycine and L-[3H]glutamate label different sites on the N-methyl-D-aspartate receptor, [3H]-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid [( 3H]AMPA) labels the quisqualate receptor and [3H]kainic acid the kainic acid receptor. The anatomical localizations of these binding sites were studied in sections of blocks removed from the cerebral cortices of eight post-mortem human brains.

Neurotensin receptors in the human spinal cord: a quantitative autoradiographic study.

The anatomical localization of neurotensin receptors in the human spinal cord was examined in 12 cases aged 4-68 years using quantitative autoradiographic methods following the incubation of fresh, unfixed cryostat sections with 4 nM [3H]neurotensin. Characterization of the pharmacological specificity of the [3H]neurotensin binding sites in the human spinal cord from displacement studies with neurotensin and various neurotensin fragments indicated that, whereas 1.0 microM neurotensin and the carboxy-terminal fragment neurotensin almost completely displaced [3H]neurotensin binding (4 nM), the amino-terminal fragments neurotensin and neurotensin1-11 were weak inhibitors.

The organization of the projection from the cerebral cortex to the striatum in the rat.

The detailed organization of the corticostriate projection has been investigated in the brain of the rat using the technique of retrograde transport of horseradish peroxidase following the placement of small, iontophoretic injections of horseradish peroxidase conjugated to lectin throughout all major regions of the striatum (caudate-putamen, nucleus accumbens and olfactory tubercle). The results demonstrate that all major regions of the cerebral cortex project to the striatum on both sides of the brain with an ipsilateral predominance. The cells of origin of both the ipsilateral and contralateral corticostriate projections lie mainly in lamina V (especially lamina Va) with very small numbers in lamina III of the neocortex and mesocortex, and in the deep laminae of the allocortex.

Benzodiazepine receptors in the human hippocampal formation: a pharmacological and quantitative autoradiographic study.

The pharmacological characteristics and anatomical distribution of benzodiazepine receptors in the human hippocampal formation were studied in seven cases aged 4-68 years. The pharmacology of the receptors was studied by computerized, non-linear least squares regression analysis of [3H]flunitrazepam displacement by flunitrazepam, CL218,872 and ethyl beta-carboline-3-carboxylate binding to membranes and the anatomical localization of these receptors was demonstrated using quantitative autoradiography following in vitro labelling of cryostat sections with [3H]flunitrazepam. The pharmacological studies indicated that the human hippocampal formation contained equal numbers of benzodiazepine receptors with high affinity (Type I) and low affinity (Type II) for CL218,872 and ethyl beta-carboline-3-carboxylate.

Connections of the paraflocculus of the cerebellum with the superior colliculus in the rat brain.

The interconnections between the paraflocculus of the cerebellum and the superior colliculus (SC) of the adult male Wistar albino rat were traced utilising the retrograde and anterograde transport of horseradish peroxidase conjugated with wheatgerm agglutinin (WGA-HRP). The study comprises three series of experiments. In the first series designed to trace the connections between the paraflocculus and the pre- and deep cerebellar nuclei, microiontophoretic injections of WGA-HRP filled either the entire paraflocculus or one of its subdivisions (ventral or dorsal paraflocculus).

The nigrotectal projection and tectospinal neurons in the rat. A light and electron microscopic study demonstrating a monosynaptic nigral input to identified tectospinal neurons.

In order to investigate the nigro-tecto-spinal pathway in the rat, the pattern of termination of nigrotectal fibres and the distribution of tectospinal neurons have been investigated in a light and electron microscopic study of the superior colliculus. In addition, the pattern of termination of nigrotectal fibres was compared to the pattern of acetylcholinesterase staining. The light microscopic studies showed that the nigrotectal fibres, which had been identified by anterograde transport of horseradish peroxidase from the substantia nigra, terminated in a distinctive clustered pattern throughout the rostrocaudal extent of the stratum griseum intermedium, stratum album intermedium and adjacent dorsal portion of the stratum griseum profundum of the ipsilateral superior colliculus.

Multiple benzodiazepine receptors in the human basal ganglia: a detailed pharmacological and anatomical study.

The pharmacological characteristics and anatomical distribution of benzodiazepine receptors in the striatum (dorsal striatum, comprising the caudate nucleus and putamen, and ventral striatum) and globus pallidus (dorsal pallidum, comprising the external and internal segments, and ventral pallidum) of the human basal ganglia were examined in twelve cases aged 4-71 years. The pharmacology of the receptors was studied using computerized, non-linear least-squares regression analysis of [3H]flunitrazepam displacement by flunitrazepam, CL218,872 and ethyl beta-carboline-3-carboxylate binding to membranes. The results showed that the dorsal striatum (caudate nucleus and putamen) contained higher concentrations of receptors than the dorsal pallidum (external and internal segments).

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.

Adult Henoch-Schönlein nephritis.

A retrospective study was performed of all patients at the Royal Adelaide Hospital over a ten-year period with biopsy proven Henoch-Schönlein nephritis. The records of 27 patients were examined, with emphasis on clinical and histopathological presentation, treatment and outcome. A scheme for assessing glomerular histology is presented, and severity correlated with prognosis of the disease.

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.

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.

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.

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.

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.

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.