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Biomedical subjects

J L Price

Publications and source records attributed to J L Price.

At least 91 records · Page 5Linked to original sources

Ultrastructure and synaptic organization of axon terminals from brainstem structures to the mediodorsal thalamic nucleus of the rat.

The ultrastructural characteristics and synaptic organization of afferent terminals from the brainstem to the mediodorsal thalamic nucleus (MD) of the rat have been studied with the electron microscope, by means of anterograde transport of wheat germ agglutinin-horseradish peroxidase (WGA-HRP). Labeled fibers were seen predominantly in the lateral portion of MD after the injections of WGA-HRP into the substantia nigra pars reticulata (SNr), the superior colliculus (SC), and the dorsal tegmental region (DT). The boutons arising from the SC were relatively small (less than 1.5 microns in diameter), formed asymmetric synaptic contacts with small dendrites and dendritic spines, and contained round synaptic vesicles. The axon terminals from the DT were mostly large boutons (2-4.5 microns) with asymmetric synaptic specializations and round vesicles. These boutons and their postsynaptic targets formed synaptic glomeruli that were entirely or partially ensheathed by glial lamellae. The ultrastructural features are almost identical to those of boutons in the medial and central segments of MD that were previously shown to originate from the basal amygdaloid nucleus and the piriform cortex. The boutons from the SNr had a wide range in size, but the majority were medium-sized to large (1.5-4 microns). The nigral boutons established symmetric synaptic contacts with dendritic shafts and occasionally with somata, and contained pleomorphic vesicles. However, like the DT terminals, they participated in glomerular formations. The nigral terminals closely resemble previously described terminals in the medial part of MD from the ventral pallidum, except that the nigral terminals formed en passant and axosomatic synapses as well as axodendritic synapses. A combined immunohistochemistry and WGA-HRP tracing study revealed that the nigral inputs were immunoreactive for glutamic acid decarboxylase and the axon terminals from the DT were immunoreactive for choline acetyltransferase. In a separate study, the colliculothalamic fibers have been shown to take up and transport the transmitter specific tracer [3H]-D-aspartate, and are therefore putatively glutamatergic and/or aspartatergic. Taken together with this, the present results suggest that the collicular afferents are excitatory and glutamatergic and/or aspartatergic, that the inputs from the DT are also excitatory and cholinergic, while the nigral inputs are inhibitory and GABAergic.

Animals↗

An ultrastructural study of neurotensin-like immunoreactive terminals in the mediodorsal thalamic nucleus of the rat.

Neurotensin-like immunoreactive (NTir) axon terminals in the mediodorsal nucleus of the thalamus (MD) in the adult rat were demonstrated by electron microscopic immunohistochemistry. Most NTir terminals were large (greater than 2 microns in diameter) with round synaptic vesicles and asymmetrical synaptic contacts although smaller (less than 1.5 microns in diameter) axon terminals were also labeled. Both types of terminals were found in the medial and central parts of MD with the greatest density in the medial part. These NTir boutons have similar ultrastructural features as anterogradely labeled terminals from the piriform cortex and the preoptic area, which have previously been identified as sources of NTir axons in MD. A few NTir boutons were also found in the medial part of MD with pleomorphic vesicles and symmetrical synaptic contacts.

Animals↗

Olfactory projections to the hypothalamus.

Electrophysiological recording, together with anterograde and retrograde axonal tracers, was used to provide a comprehensive description of the origin and distribution of the olfactory input to the lateral hypothalamus. This input was much more substantial to the caudal part of the hypothalamus than to the rostral part and originates from several different areas of the olfactory cortex. Positive responses to electrical stimulation of the olfactory bulb were found consistently in the postero-lateral hypothalamus, but only occasionally at more rostral levels. In agreement with this, injections of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) in the posterior half of the lateral hypothalamus labeled cells in four cortical areas that receive input from the olfactory bulb: the anterior olfactory nucleus, the piriform cortex (in the deepest layer or ventral endopiriform nucleus), the olfactory tubercle (in the deep polymorphic layer), and the anterior cortical nucleus of the amygdala. Injections of WGA-HRP in the anterolateral hypothalamus labeled cells only in the anterior cortical nucleus of the amygdala. Anterograde axonal tracing confirmed these projections. Injections of 3H-leucine in the anterior olfactory nucleus, the piriform cortex, and the olfactory tubercle produced axonal label that was light and confined to the medial forebrain bundle in the rostral hypothalamus but was more substantial and extended throughout the lateral hypothalamic area caudally. Injections in the anterior cortical amygdaloid nucleus labeled axons in the anterior hypothalamus and in the premammillary nuclei as well as in the posterolateral hypothalamic area. In addition, a projection was demonstrated to the nuclei gemini from the polymorphic zone deep to the olfactory tubercle. Injections of two fluorescent retrograde tracers into the mediodorsal nucleus of the thalamus and the posterolateral hypothalamus showed that cells projecting to both diencephalic sites were intermingled in all of the olfactory cortical areas except the anterior olfactory nucleus, where cells were labeled only from the hypothalamus. In the deep layer of the piriform cortex and in the anterior cortical amygdaloid nucleus cells were also double labeled, indicating that they send collateral axons to both parts of the diencephalon.

Amygdala↗

Synaptic organization of projections from basal forebrain structures to the mediodorsal thalamic nucleus of the rat.

The synaptic organization of the mediodorsal thalamic nucleus (MD) in the rat was studied with the electron microscope, and correlated with the termination of afferent fibers labeled with wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). Presynaptic axon terminals were classified into four categories in MD on the basis of the size, synaptic vesicle morphology, and synaptic membrane specializations: 1) small axon terminals with round synaptic vesicles (SR), which made asymmetrical synaptic contacts predominantly with small dendritic shafts; 2) large axon terminals with round vesicles (LR), which established asymmetrical synaptic junctions mainly with large dendritic shafts; 3) small to medium axon terminals with pleomorphic vesicles (SMP), which formed symmetrical synaptic contacts with somata and small-diameter dendrites; 4) large axon terminals with pleomorphic vesicles (LP), which made symmetrical synaptic contacts with large dendritic shafts. Synaptic glomeruli were also identified in MD that contained either LR or LP terminals as the central presynaptic components. No presynaptic dendrites were identified. In order to identify terminals arising from different sources, injections of WGA-HRP were made into cortical and subcortical structures known to project to MD, including the prefrontal cortex, piriform cortex, amygdala, ventral pallidum and thalamic reticular nucleus. Axons from the amygdala formed LR terminals, while those from the prefrontal and insular cortex ended exclusively in SR terminals. Fibers labeled from the piriform cortex formed both LR and SR endings. Based on their morphology, all of these are presumed to be excitatory. In contrast, the axons from the ventral pallidum ended as LP terminals, and those from the thalamic reticular nucleus formed SMP terminals. Both are presumed to be inhibitory. At least some terminals from these sources have also been identified as GABAergic, based on double labeling with anterogradely transported WGA-HRP and glutamic acid decarboxylase (GAD) immunocytochemistry.

Amygdala↗

Retrospective postmortem dementia assessment. Validation of a new clinical interview to assist neuropathologic study.

Neuropathologic studies of dementia and normal aging suffer from a lack of individuals examined for the presence and severity of dementia before death. To increase clinical information in such cases, a retrospective collateral interview was developed. Thirty-nine individuals were studied; 27 had autopsies. In all cases, the autopsy confirmed the Retrospective Collateral Dementia Interview (RCDI) diagnosis of the presence or absence of dementia; the RCDI had a sensitivity of 88% and a specificity of 80% for specifically detecting probable Alzheimer's disease. Agreement between the RCDI and premortem diagnosis was 96%; between RCDI and medical records, 100%. Agreement between RCDI staging of dementia severity and the last assessment of the living subject was 70%; between the RCDI and a brief staging at death, 86%. This validation confirms the value of postmortem interviews with close informants to assess dementia presence and severity.

Aged↗

Very mild Alzheimer's disease: informant-based clinical, psychometric, and pathologic distinction from normal aging.

We compare clinicopathologic data from 10 subjects identified in the very mild stage of senile dementia of the Alzheimer type with findings from similar studies in four cognitively normal subjects. We based the diagnosis of very mild dementia in the 10 subjects on informant reports and the judgment of experienced clinicians. Deficits of some psychometric measures of memory, language, and speeded psychomotor performance were observed for these subjects. The histologic markers of Alzheimer's disease, including neurofibrillary tangles and both the "diffuse" and classic subtypes of senile plaques, were present in the neocortex in all 10 subjects but essentially were absent in the four controls. These findings indicate that even "questionable" dementia can be diagnostic for Alzheimer's disease. Furthermore, because truly normal aging may be unaccompanied by neocortical senile plaques and neurofibrillary tangles, the presence of these lesions should suggest the possibility of clinically undetected Alzheimer's disease.

Activities of Daily Living↗

Sources of presumptive glutamatergic/aspartatergic afferents to the magnocellular basal forebrain in the rat.

The distribution of presumptive glutamatergic and/or aspartatergic neurons retrogradely labeled following injections of [3H]-D-aspartate into the magnocellular basal forebrain of the rat was compared with the distribution of neurons labeled by comparable injections of the nonspecific retrograde axonal tracer wheat germ agglutinin conjugated to horseradish peroxidase. Cells retrogradely labeled by wheat germ agglutinin-horseradish peroxidase were found in a wide range of limbic and limbic-related structures in the forebrain and brainstem. In the telencephalon, labeled neurons were seen in the orbital, medial prefrontal, and agranular insular cortical areas, the amygdaloid complex, and the hippocampal formation. Labeled cells were also seen in the olfactory cortex, the lateral septum, the ventral striatopallidal region, and the magnocellular basal forebrain itself. In the diencephalon, neurons were labeled in the midline nuclear complex of the thalamus, the lateral habenular nucleus, and the hypothalamus. In the brainstem, labeled cells were found bilaterally in the ventral midbrain, the central gray, the reticular formation, the parabrachial nuclei, the raphe nuclei, the laterodorsal tegmental nucleus, and the locus coeruleus. A significant fraction of the afferents to the magnocellular basal forebrain appear to be glutamatergic and/or aspartatergic. Only a few of the regions labeled with wheat germ agglutinin-horseradish peroxidase were not also labeled with [3H]-D-aspartate in the comparable experiments. Most prominent among the non-glutamatergic/aspartatergic projections were those from fields CA1 and CA3 of the hippocampus, the hilus of the dentate gyrus, the dorsal subiculum, the tuberomammillary nucleus, and the ventral pallidum. In addition, most of the lateral hypothalamic and brainstem projections to the magnocellular basal forebrain were not significantly labeled with [3H]-D-aspartate. In addition to these inputs, a commissural projection from the region of the contralateral nucleus of the horizontal limb of the diagonal band was confirmed with both wheat germ agglutinin-horseradish peroxidase and the anterograde axonal tracer Phaseolus vulgaris leucoagglutinin. This projection did not label with [3H]-D-aspartate or [3H]-GABA, suggesting that it is not glutamatergic/aspartatergic or GABAergic. Furthermore, double labeling experiments with the fluorescent retrograde tracer True Blue and antibodies against choline acetyltransferase indicate that the projection is not cholinergic.

Afferent Pathways↗

Postnatal changes in the density and distribution of neurotensin-like immunoreactive fibers in the mediodorsal nucleus of the thalamus in the rat.

A previous report (Inagaki et al., Brain Res. 260:143-146, '83) suggested that the peptide neurotensin is contained in neurons of the piriform cortex that project to the mediodorsal thalamic nucleus (MD) in young rats. To confirm this, we have studied the distribution of neurotensin-like immunoreactive (NTIR) fibers in MD during development, using three antisera directed at different parts of the neurotensin molecule (Emson et al., J. Neurochem. 38:992-999, '82). In adult rats, NTIR fibers in MD are sparse. They are located mostly at the medial edge of MD and in the adjacent midline thalamic nuclei, with a few poorly stained NTIR fibers in the central part of MD. In contrast, during the first postnatal week, both the medial and central portions of MD stain heavily for neurotensin. The density of NTIR fibers in MD then progressively decreases until the density typical of adult rats is reached, at about 5 weeks. Changes in the distribution of NTIR fibers in MD also occur. In 7-day-old rats, the patches of NTIR fibers in the medial and central parts of MD are contiguous, but by 10 days a sparsely immunoreactive zone forms between them. With maturation, this zone enlarges as the density of neurotensin staining decreases, until the medial contingent of NTIR fibers reaches its adult position at the medial edge of MD. From a comparison of the distribution of NTIR cells with that of cells that can be retrogradely labeled from MD or the midline thalamus, the probable source of the NTIR fibers to the central part of MD is in the deep layer of the piriform cortex, while the NTIR fibers to the medial edge of MD and the midline nuclei may arise from the preoptic region and the medial amygdala. In neonatal rats, neurons are found in the piriform cortex, the preoptic region, and the medial amygdala, which can be double-labeled both for neurotensin and with a retrograde tracer injected into MD and the midline thalamus. Projections of the preoptic region to the thalamus have a distribution similar to that of the medial population of NTIR fibers, whereas the distribution of piriform cortical afferents in central MD matches the central patch of NTIR fibers.

Aging↗

The Io syndrome: symptom formation in victims of sexual abuse.

The sexual abuse of women today is analyzed alongside the mythology of Ovid's Metamorphoses. Two thousand years ago, Ovid unfolded a world view of human beliefs and practices that make up today's symptom formation and psychodynamic in victims of sexual abuse. Herewith the mythology of Io. Her rape and subsequent symptom formation is understood as a clinical account of rape-trauma syndrome and post-traumatic stress disorder.

Adult↗

Neuroanatomical correlates of a lactate-induced anxiety attack.

Positron emission tomographic measurements of regional blood flow were used to assess local neuronal activity in patients with panic disorder and in normal control subjects before and during the infusion of sodium lactate. A new technique for the analysis of positron emission tomographic data was employed to identify significant changes in regional blood flow associated with lactate infusion in the panicking patients, nonpanicking patients, and controls. Lactate-induced panic was associated with significant blood flow increases bilaterally in the temporal poles; bilaterally in insular cortex, claustrum, or lateral putamen; bilaterally in or near the superior colliculus; and in or near the left anterior cerebellar vermis. Lactate infusion was not associated with significant changes in regional blood flow in the nonpanicking patients or control subjects. Thus, the identified regions seemed to be involved in an anxiety attack.

Adult↗

Putative glutamatergic and/or aspartatergic cells in the main and accessory olfactory bulbs of the rat.

The "transmitter-specific" retrograde axonal tracer 3H-D-aspartate has been used to demonstrate neurons in the olfactory bulb which putatively utilize aspartate and/or glutamate as their neurotransmitter and which send an axon either to the piriform cortex or within the bulb itself. Injections of 3H-D-aspartate into layer I of the anterior piriform cortex, in the zone of termination of axons from the olfactory bulb, labeled only a few cells in the main olfactory bulb, located in the mitral and external plexiform layers. Although these cells resembled mitral and tufted cells, they tended to have smaller somata than other mitral or tufted cells and apparently form a distinct subpopulation of relay cells. In contrast, many of the mitral cells of the accessory olfactory bulb were labeled by the same injections of 3H-D-aspartate, probably as a result of involvement of the accessory olfactory tract or its bed nucleus in the injection site. Similar injections of the "nonspecific" tracer HRP into the anterior piriform cortex labeled most of the cells in the mitral cell layer of both the main and accessory olfactory bulbs, and some tufted cells in the external plexiform layer. It is concluded that only a small, distinct subpopulation of the mitral or tufted cells of the main olfactory bulb are aspartatergic and/or glutamatergic, while many (at least) of the mitral cells of the accessory olfactory bulb use the excitatory amino acids as transmitters. Injections of 3H-D-aspartate directly into the main olfactory bulb also failed to label the mitral and deeply situated tufted cells. However, a few cells were labeled in the periglomerular region, the superficial external plexiform layer, and the granule cell layer near the injection site. These labeled cells were smaller than mitral and tufted cells but generally larger than periglomerular or granule cells. They may represent a population of glutamatergic or aspartatergic short axon cells. In addition, small cells of an unknown type were labeled in the olfactory nerve layer following injections in the deepest part of the bulb. These cells do not correspond to any of the well characterized cell types of the olfactory bulb.

Animals↗

Strategic planning in patient education: a key element of successful management.

Strategic Planning is a useful technique for patient education planning in health care facilities. The consultants to the planning process at a Veterans Administration Medical Center outline the lessons of strategic planning in an effort to guide and encourage newcomers. The Seattle VA Medical Center planning outcomes are described to emphasize the benefits. The authors enthusiastically recommend strategic planning as a management tool for patient education committees.

Hospital Bed Capacity, 300 to 499↗

Prefrontal-limbic epilepsy: experimental functional anatomy.

Nonconvulsive seizures from prefrontal cortex in humans cause complex behavioral, motor, and autonomic manifestations. In order to gain insight into the possible anatomical basis of these phenomena, we have studied experimental seizures from medial and lateral prefrontal-limbic cortex and the amygdaloid complex in rat. Small injections of penicillin or electrical stimulation were used to induce seizures, and the [14C]deoxyglucose technique was employed to map pathways of seizure spread. Analysis of results indicates that prefrontal-limbic cortex and amygdala exhibit strong bilateral reciprocal interaction. Mild seizures from these different areas activated both unique and similar pathways and targets. With increasing strength of discharge from these areas, there was a convergence of the subcortical pattern of activation in medial and midline thalamic nuclei and bilateral substantia nigra. These studies suggest that complex epileptic phenomena in humans evoked from a prefrontal seizure focus relate to activation of cortical and subcortical functional limbic anatomy.

Amygdala↗