Biomedical subjects

S J Bacon

Publications and source records attributed to S J Bacon.

At least 19 recordsLinked to original sources

PubMed1996

Amygdala input to medial prefrontal cortex (mPFC) in the rat: a light and electron microscope study.

This paper describes the termination pattern and synaptic connectivity of the pathway from the basolateral nucleus of the amygdala (BLA) to the medial prefrontal cortex (mPFC; areas 25, 32, and 24b) of the rat. Discrete injections of the anterograde tracer Phaseolus vulgaris-leucoagglutinin (PHA-L) were made in the BLA and detailed light microscopical observations made of the distribution of PHA-L labelled fibres and boutons in the mPFC. Labelled fibres were distributed in two tiers: predominantly within deep layer 1/layer 2 and also in layers 5/6. Fibre plexi in layers 2 and 5 were highly varicose. Electron microscopical examination of 120 labelled boutons in area 32 (60 in layer 2 and 60 in layer 5) indicated that 116 (97%) established asymmetrical synaptic contacts with dendritic spines and 4 (3%) were in synaptic contact with small dendritic shafts. No significant differences in target structures were found between layers 2 and 5. The results indicate that BLA input to mPFC in the rat predominantly innervates spine bearing dendrites in layers 2 and 5. This suggests that the neuronal operations of these processes are influenced by direct feedforward excitation from the BLA.

Afferent Pathways↗

PubMed1996

Localisation of NADPH diaphorase activity and NOS immunoreactivity in astroglia in normal adult rat brain.

This study demonstrates the co-localisation of NADPH diaphorase activity and GFAP immunoreactivity in non-neuronal cells in weakly fixed brain sections from normal adult rats. The presence of GFAP immunoreactivity in these cells indicates that they are astroglia. In addition, cells possessing the morphological characteristics of astroglia were weakly immunoreactive for the endothelial isoform of nitric oxide synthase (eNOS)--these cells also co-localised NADPH diaphorase activity. Furthermore, cells immunoreactive for eNOS displayed GFAP immunoreactive processes. This cytochemical evidence strongly suggests that resting astroglia are potential sources of nitric oxide--a powerful modulator of cell activity.

Animals↗

PubMed1996

Local circuit neurons in the medial prefrontal cortex (areas 24a,b,c, 25 and 32) in the monkey: I. Cell morphology and morphometrics.

This paper provides a comprehensive morphological description of local circuit neurons in the medial prefrontal cortex (mPFC: areas 24a, 24b, 24c, 25 and 32) of the monkey. Cortical interneurons were identified immunocytochemically by the expression of the calcium binding proteins calretinin (CR), parvalbumin (PV) and calbindin D-28k (CB). Interneurons were also identified using GABA immunocytochemistry. The areal and laminar distributions of CR, PV, and CB cells were consistent across mPFC; their morphological characteristics identified them as local circuit neurons. Throughout layers 2-6: CR immunoreactivity labelled double bouquet and bipolar neurons, PV was localised in large and small basket neurons and in chandelier (axoaxonic) cells, while CB immunoreactivity was present in double bouquet, Martinotti, and neurogliaform neurons. In addition, some cells in layer 1 (including Cajal-Retzius neurons) were CR immunoreactive. Calbindin immunoreactivity also labelled a population of large nonpyramidal neurons deep in the cortex. Other types of CR, PV and CB cells were also immunolabelled. A small population of layer 3 pyramidal cells was weakly CB immunoreactive. Peak cell densities occurred in layer 2/upper layer 3 for CR+ neurons and in upper to midlayer 3 for CB+ cells. PV+ neuron density peaked in midcortex. These observations support and extend a similar study of monkey prefrontal cortex (Condé et al. [1994] J. Comp. Neurol. 341:95-116). The morphologies and combined cortical depth distributions of CR+, PV+, and CB+ neurons were similar to GABA-immunolabelled cells. Local circuit neurons in mPFC displaying NADPH diaphorase activity composed less than 0.25% of the total neuron population, and were distributed in two horizontal strata, in mid- to lower layer 3 and in lower layer 5/upper layer 6. CR, PV and CB immunoreactivity was colocalised in NADPH diaphorase-reactive neurons. The interrelationships between CR+, PV+ and CB+ neurons were investigated using dual immunocytochemistry. CR+ puncta were found to be closely associated with the cell bodies and proximal processes of PV+ neurons, whereas CR+ puncta were located more distally over processes from CB+ cells. Additionally, PV+ puncta were found closely apposed to PV+ somata and processes and CR+ puncta abutted against CR+ cell bodies. The companion paper (Gabbott and Bacon [1996] J. Comp. Neurol.) presents quantitative data regarding the areal and laminar distributions of the identified cell classes in mPFC. Such data provide a realistic structural framework with which to investigate neuronal operations in monkey mPFC.

Animals↗

PubMed1996

Local circuit neurons in the medial prefrontal cortex (areas 24a,b,c, 25 and 32) in the monkey: II. Quantitative areal and laminar distributions.

The companion paper (Gabbott and Bacon [1996] J. Comp. Neurol.) describes the morphology of calretinin (CR)-, parvalbumin (PV)-, calbindin (CB)-, and GABA-immunoreactive neurons, and NADPH diaphorase-reactive cells, in the medial prefrontal cortex (mPFC; areas 24a, 24b, 24c, 25 and 32) of the adult monkey. Since these local circuit neurons play crucial functional roles, the aim of this study was to provide supportive quantitative data defining their areal and laminar distribution in mPFC. The numerical densities of neurons (Nv, number of cells per mm3) in each area and layer were calculated stereologically. The mean total neuronal NV estimates across mPFC was 55,727 +/- 3,319 per mm3 (mean +/- S.D.; n = 3); values ranged from 50,489 +/- 8,374 per mm3 (area 24a) to 59,938 +/- 7,214 per mm3 (area 24c). Interareal differences were not significant. Cortical depth measurements and neuronal NV estimates for each area allowed the absolute number of neurons in a column of cortex under 1 mm2 of surface to be calculated; values varied between 86,457 +/- 15,063 (area 24a) and 128,464 +/- 24,050 (area 24c). Using immunolabelled Nissl-stained sections of mPFC, CR+ neurons constituted 11.2%, PV+ neurons 5.9%, and CB+ neurons 5.0% of the total neuron population. GABA+ neurons represented an overall 24.9% (23.5-27.3%) of neurons in the mPFC. Differences between areas were not significant. The cortical depth distribution histograms of CR+, PV+, CB+, and GABA+ cell populations in each area were derived and the percentage of a given cell population in each layer subsequently calculated. Peaks in the cortical depth distributions of CR+ and CB+ neurons occurred in layer 2 and upper layer 3, respectively; the peak distribution of PV+ neurons occurred between lower layer 3 and upper layer 5. The depth distribution of GABA+ cells reflected the combined distributions of CR+, PV+ and CR+ neurons. In all areas, the majority (74.4-84.0%) of the GABA cell population was located in layers 2/3. The depth distributions for each cell type were similar between areas. Diaphorase-reactive neurons accounted for 0.25% (0.2-0.32%) of all cortical neurons in mPFC and were distributed in two horizontal strata, in midlayer 3 and in mid/upper layer 6. A large population of diaphorase-reactive cells was present in the white matter. The absolute numbers of CR+, PV+, CB+ and GABA+ neurons within individual layers in a column of cortex under 1 mm2 and 50 x 50 microns of cortical surface have been derived. The data presented provide the basis for a quantitative definition of cortical circuits in monkey mPFC.

Afferent Pathways↗

PubMed1995

Co-localisation of NADPH diaphorase activity and GABA immunoreactivity in local circuit neurones in the medial prefrontal cortex (mPFC) of the rat.

This study provides evidence that neurones in the medial prefrontal cortex of the rat (mPFC areas 24b, 25, and 32) containing strong NADPH diaphorase reactivity also contain GABA immunoreactivity. Also demonstrated is the co-localisation of NADPH diaphorase activity with immunoreactivity for the neuronal isoform of nitric oxide synthase (nNOS) in mPFC neurones. Qualitative and quantitative analyses in the light and electron microscopes indicate that strongly NADPH diaphorase reactive cells are a subpopulation of GABAergic local circuit neurones and constitute a very small proportion (0.6-1.1%) of neurones in rat mPFC. These results suggest that NADPH diaphorase reactive cells in rat mPFC can influence neural activity via GABA-mediated and NO-mediated mechanisms.

Animals↗

PubMed1995

Dendritic spine density of NADPH diaphorase reactive neurons in the medial prefrontal cortex (mPFC) of the rat.

The density of spines has been calculated over the processes of NADPH diaphorase reactive neurons in the medial prefrontal cortex (mPFC) of the rat. Quantitative data indicate that diaphorase reactive dendrites ranged from being virtually aspiny to possessing moderate numbers of spines (0.66 +/- 0.23 spines/microns; mean +/- S.D.). The size and shape of dendritic spines varied from long thin 'drum sticks' (the most frequent type) to short stubby protrusions.

Animals↗

PubMed1994

Two types of interneuron in the dorsal lateral geniculate nucleus of the rat: a combined NADPH diaphorase histochemical and GABA immunocytochemical study.

The rationale for this study was to provide a comprehensive light microscopical description of the morphology of diaphorase-reactive neurons and neuropil elements in the dorsal lateral geniculate nucleus (dLGN) of the rat. An additional objective was to quantitatively assess whether a subpopulation of the diaphorase-reactive neurons, previously shown to be GABA-immunoreactive, constitute a distinct type of local-circuit neuron in the rat dLGN. Diaphorase activity was localised in a population of predominantly bipolar fusiform neurons. These cells were weak to moderately stained and possessed the morphological features of intrinsic inhibitory neurons, previously called class B neurons in the rat dLGN. Quantitative estimates indicated that the diaphorase-reactive neurons constituted approximately 10% of the total neuron composition of the dLGN. The majority (about 83%) of the diaphorase-reactive cells were located in the lateral half of the nucleus. In addition, a dense plexus of diaphorase-reactive varicose fibres was found throughout the dLGN lying between the oriented fibre bundles coursing dorsoventrally through the LGN. Diaphorase-reactive punctae were found to be closely associated with the somata and proximal dendritic segments of nonreactive neurons and also with the stained proximal dendritic segments of diaphorase-reactive dLGN neurons. The source of the diaphorase-reactive fibres in the dLGN was unknown. Evidence suggests, however, that they are of extrinsic origin. The GABA-immunoreactive nature of the diaphorase neurons in the dLGN was demonstrated by colocalising GABA immunoreactivity within the somata of diaphorase-reactive cells. The majority (> 90%) of diaphorase-reactive dLGN neurons were GABA-immunopositive. Also present was a distinct population of GABA-immunopositive neurons that were not diaphorase-reactive. In this study, cells that were solely GABA-immunopositive have been called class B1 neurons, while cells that were both diaphorase-reactive and GABA-immunoreactive have been called class B2 neurons. Size-frequency distributions of somatic profile areas established that the two populations of GABA-immunoreactive neuron were significantly different. Class B1 neurons constituted 57%, with class B2 cells representing 43% of all GABA-immunostained neurons in the rat dLGN. The characteristic morphological features, neurochemical identity and frequency of the diaphorase-reactive neurons in the rat dLGN indicate that they represent a subpopulation of inhibitory interneurons with the ability to affect intrinsic dLGN operations and thalamocortical interactions using the neuromodulator nitric oxide.

Animals↗

PubMed1994

Multiple factors determine the sex ratio of postpartum-conceived Norway rat litters.

When Norway rat litters are nursed communally, postpartum-conceived litters born asynchronously are female biased at birth. To determine if one or more mechanisms produced this sex ratio bias, we studied litters conceived at a postpartum estrus, and systematically varied the presence or absence of a litter suckling during gestation. Four different factors biased the sex ratio of postpartum-conceived litters. Postpartum condition, implantation in a single uterine horn, and very large litter size favored the birth of female pups. The presence of suckling pups during gestation, on the other hand, brought the sex ratio up to parity. Each factor operated at or before implantation, and apparently did so asymmetrically in the two horns of the uterus. Thus, a litter's sex ratio at birth, even a sex ratio of parity, can be the result of multiple mechanisms of bias, some working in opposition to each other. Theories of sex ratio biasing must incorporate multiple mechanisms rather than focusing on single mechanisms within a given species.

Animals↗

PubMed1994

An oriented framework of neuronal processes in the ventral lateral geniculate nucleus of the rat demonstrated by NADPH diaphorase histochemistry and GABA immunocytochemistry.

This study investigated the morphology and quantitative distribution of neurons containing NADPH diaphorase activity in the ventral lateral geniculate nucleus of the rat. The pattern of diaphorase staining revealed a strongly reactive lateral subdivision and a weakly staining medial subdivision. A characteristic feature of the diaphorase staining in the lateral part was its "stripe-like" appearance. These "diaphorase stripes" resulted from regions of strong somatic and neuropil diaphorase activity lying between unstained fibre bundles coursing dorsoventrally through the nucleus. Two distinct populations of diaphorase reactive cell types were present--class A and class B neurons. The ratio of class A to class B diaphorase neurons was approximately 14:1 (A:B). Diaphorase reactive neurons made up 73% of the total neuron population in the lateral subdivision, and 31% in the medial subdivision. A third population of cells was found exclusively in the optic tract--class C neurons. Quantitative analyses in the coronal and sagittal planes indicated that the principal processes of both class A and class B neurons were oriented preferentially--either parallel with, or perpendicular to the outlying optic tract. Diaphorase enzyme histochemistry in combination with GABA immunocytochemistry demonstrated the co-localization of GABA immunoreactivity in the majority of class B neurons, whereas class A and class C neurons were GABA immunonegative. Furthermore a large population of GABA-immunoreactive neurons was present that were not stained for diaphorase activity. From this and previous studies, it can be concluded that a high proportion of the diaphorase reaction class A neurons are geniculotectal projection cells, while diaphorase reaction class B neurons represent a numerically small subpopulation of "local-circuit" inhibitory neurons. Since diaphorase activity co-localizes with nitric oxide synthase, the results indicate the likely involvement of nitric oxide in the neuronal operations of both subpopulations of geniculotectal projection neurons and "local-circuit" GABAergic neurons in the rat's ventral lateral geniculate nucleus.

Aging↗

PubMed1993

Histochemical localization of NADPH-dependent diaphorase (nitric oxide synthase) activity in vascular endothelial cells in the rat brain.

This study investigated the localization of NADPH-dependent diaphorase activity within vascular endothelial cells in the rat brain. Light microscope observations showed that in addition to neurons and neuronal processes stained histochemically for NADPH-dependent diaphorase activity, endothelial cells in many medium to large diameter (20-100 microns) blood vessels were also stained. These vessels were either attached to the pial surface or contained within the substance of the tissue. In vascular endothelia, the formazan end-product of the diaphorase reaction was deposited as discrete clusters of darkly stained punctae that were located around the nucleus of these cells. Correlated light- and electron-microscopical examination revealed that the sites of formazan deposition occurred in regions of endothelial cytoplasm devoid of smooth and rough endoplasmic reticulum and of mitochondria. Since endothelial NADPH dependent diaphorase activity co-localizes with the activity of nitric oxide synthase (the synthetic enzyme for nitric oxide) these observations suggest that in vascular endothelial cells nitric oxide synthase may be a highly localized soluble cytosolic enzyme not structurally associated with any subcellular organelle. In addition, specific regions of the smooth muscle cells encircling the larger diameter blood vessels clearly demonstrated NADPH dependent diaphorase activity. Unmyelinated fibres and fibre-plexi surrounding blood vessels on the pial surface were also stained. The results of this study show specific NADPH dependent diaphorase activity in vascular endothelial cells in the rat brain. Therefore, together with neurons, endothelial cells may control nitric oxide-dependent vasodilation thereby regulating local blood flow in the brain.

Amino Acid Oxidoreductases↗

PubMed1993

A monosynaptic pathway from an identified vasomotor centre in the medial prefrontal cortex to an autonomic area in the thoracic spinal cord.

Chemical microstimulation (1 mM L-glutamate or 25 mM KCl) of the medial prefrontal cortex of anaesthetized rats produced falls in systolic and diastolic blood pressure of similar magnitude, without a change in heart rate. Application of the lectin Phaseolus vulgaris leucoagglutinin by iontophoresis from an adjacent barrel of the same micropipette revealed a direct projection to the central autonomic area of the thoracic spinal cord from this vasomotor area, which is equivalent to the region called prelimbic cortex by Krettek and Price [J. comp. Neurol. (1977) 171, 157-192] or Cg3 by Paxinos and Watson [The Rat Brain in Stereotaxic Coordinates (1986)]. Labelled axons descended in the dorsal corticospinal tract in the cervical spinal cord, where they displayed a few varicosities. In the thoracic spinal cord, labelled fibres occurred bilaterally in the gray matter, predominantly in the central autonomic area, where they displayed many varicosities. Electron microscope studies revealed that the anterogradely labelled varicosities in the central autonomic area were vesicle-filled boutons that formed asymmetric synaptic contacts. The synaptic targets were small dendrites or dendritic protrusions that were characterized by a high incidence of multivesicular bodies and coated vesicles. We conclude that a monosynaptic pathway that originates from a physiologically-defined vasomotor area in the medial prefrontal cortex terminates on a characteristic type of neuron in the central autonomic area of the thoracic spinal cord.

Animals↗

PubMed1990

Electron microscopic evidence of a monosynaptic pathway between cells in the caudal raphé nuclei and sympathetic preganglionic neurons in the rat spinal cord.

Electrophysiological and anatomical studies have suggested the existence of a pathway between the caudal raphé nuclei and regions of the spinal cord containing the sympathetic preganglionic neurons. However synaptic connections between cells in the raphé nuclei and identified sympathetic preganglionic neurons have not yet been shown. We have used a combination of anterograde tracing using Phaseolus vulgaris leucoagglutinin (PHA-L), retrograde tracing using a conjugate of cholera B chain and HRP and electron microscopy to look for such a pathway in rats. When PHA-L had been injected into the regions mainly restricted to the raphé pallidus and raphé magnus, synaptic contacts were found between PHA-L containing terminals and preganglionic neurons retrogradely labelled from the adrenal medulla. Out of the 43 synaptic contacts analysed, 26 were onto somata and 14 onto dendrites. 75% of the total appeared to have symmetric membrane specialisations, 20% asymmetric and the remainder could not be classified. Synaptic contacts were not seen in an animal in which the PHA-L injection site involved cells in the ventral raphé obscurus and surrounding gigantocellular reticular formation. These findings provide evidence of the existence of a direct monosynaptic pathway between cells in the raphé pallidus and/or caudal raphé magnus, and identified sympathetic preganglionic neurons and give further support for a role for the caudal raphé nuclei in sympathetic autonomic regulation.

Adrenergic Fibers↗

PubMed1988

A simple and rapid method for the production of cholera B-chain coupled to horseradish peroxidase for neuronal tracing.

A simple and rapid method is described for the production of cholera B-chain coupled to horseradish peroxidase suitable for neuronal tracing. Horseradish peroxidase was activated with a mild sodium periodate oxidation followed by incubation with the cholera B-chain, to yield the conjugates, samples of which were fractionated further by size exclusion chromatography. Both fractionated material and unfractionated conjugates were tested in vitro by a binding assay on rat synaptic membranes, and in vivo by their ability to undergo retrograde transport following injection into the adrenal medulla of rats. These assays showed that the unfractionated conjugates were equivalent to the fractionated conjugates in binding to the rat synaptic membranes, and that they both provided good retrograde labelling of neurones in the spinal cord after injection into the adrenal medulla, with extensive labelling of the distal dendrites.

Animals↗

PubMed1988

Preganglionic sympathetic neurones innervating the rat adrenal medulla: immunocytochemical evidence of synaptic input from nerve terminals containing substance P, GABA or 5-hydroxytryptamine.

Sympathetic preganglionic neurones that innervate the adrenal medulla were identified for subsequent light and electron microscopic study by the retrograde transport of horseradish peroxidase (HRP) or a conjugate of HRP and cholera B-chain. Most labelled neurones were found in the intermediolateral column, but some occurred in the intercalated nucleus and in the lateral funiculus of the thoracic spinal cord. Three morphologically distinct types of neurone were retrogradely labelled, two of which had dendrites that extended medially towards the central canal and laterally across the entire lateral funiculus. A combination of retrograde labelling with pre-embedding immunocytochemistry allowed us to demonstrate synaptic contacts between boutons immunoreactive for substance P or 5-hydroxytryptamine (5-HT) and the cell bodies or proximal dendrites of sympathoadrenal neurones. The 5-HT-immunoreactive boutons appeared to be of two morphologically distinct types. Postembedding immunocytochemistry enabled us to show that sympathoadrenal neurones receive a heavy synaptic innervation from GABA-immunoreactive boutons: 32% of a random series of boutons in synaptic contact with cell bodies were GABA-immunoreactive. Proximal dendrites and also distal dendrites within the white matter were ensheathed in synaptic boutons, 37% of which were GABA-immunoreactive. It is concluded that sympathoadrenal neurones receive at least 4 distinct types of afferent synaptic input: from neurones containing substance P, or GABA and from two types of neurones containing 5-HT. The presence of synaptic inputs on distal dendrites that extend across the white matter adds further complexities to the control of the activity of sympathetic preganglionic neurones.

Adrenal Medulla↗

PubMed1988

Degeneration of serotonin-specific neurons in the brain in experimental Trypanosoma brucei infection.

ORMEROD and HUSSEIN (1986) have shown that an intracellular stage of Trypanosoma brucei rhodesiense causes the destruction of ependymal cells lining the ventricles of the brain. The ventricular ependymal cells are intimately associated with a plexus of nerves that react specifically with monoclonal antibody raised against serotonin. We have shown that in areas where the ependyma is damaged, the supraependymal plexus also undergoes destruction and that retrograde degeneration of the neuron as far as the dorsal raphe nucleus also occurs. Although the work is as yet unfinished, we suggest that some of the neuro-psychological changes, observed in clinical sleeping sickness, may be the result of this lesion.

Animals↗

PubMed1985

A modified histochemical technique to visualize acetylcholinesterase-containing axons.

An improved histochemical method for light microscopic demonstration of acetylcholinesterase (AChE) has been developed. Axonal, dendritic, and perikaryal staining are well delineated, both in areas of low AChE content, such as cerebral cortex, and in areas of high AChE content, such as neostriatum. Axonal staining, including arborizations, stands out against a clear background devoid of diffuse reaction product.

Acetylcholinesterase↗

PubMed1984

Acetylcholinesterase-immunoreactive axonal network in monkey visual cortex.

Immunocytochemistry with antibodies to human erythrocyte acetylcholinesterase (AChE) was used to demonstrate axons containing this enzyme in the visual cortex (area 17) of macaques. AChE-positive fibers were most dense in layers I, IIIB, IV, and VIB of Hassler and Wagner (I, IVA, IVC, and VIB of Brodmann) with three strata of more sparsely distributed fibers (layers II-IIIA, IIIC, and V-VIA of Hassler and Wagner [II-III, IVB, and V-VIA of Brodmann]). Layer I contained the most dense plexus of AChE-positive axons, oriented horizontally. Horizontally oriented axons were also located in layers IIIB, IIIC, IV, and V of Hassler and Wagner (IVA, IVB, IVC, and V of Brodmann). Layer VIB contained axons of variable orientation, apparently afferent to cortex. Moderately stained neuronal perikarya were occasionally encountered in layer VIB and superficial white matter, but no intensely stained neurons were seen.

Acetylcholine↗

PubMed1983

Immunocytochemical identification of cholinergic neurons in the monkey central nervous system using monoclonal antibodies against choline acetyltransferase.

A monoclonal antibody directed against rat brain choline acetyltransferase (ChAT) was used to stain cholinergic nerve cells within the brain and spinal cord of macaques. ChAT immunoreactivity was seen in motor neurons of the brainstem and spinal cord, in large neurons of the striatum, and in large neurons in the basal forebrain (medial septum--diagonal band--nucleus basalis complex); each of these groups of neurons is believed to be cholinergic. The ability to visualize cholinergic neurons in the nervous system of primates provides a new approach to the study of cholinergic systems in health and disease.

Animals↗