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Biomedical subjects

S L Foote

Publications and source records attributed to S L Foote.

At least 55 records · Page 3Linked to original sources
PubMed1987

Corticotropin-releasing factor disrupts sensory responses of brain noradrenergic neurons.

In order to elucidate the possible role of noradrenergic neurons of the nucleus locus coeruleus (LC) in stress responses, the effects of corticotropin-releasing factor (CRF) on LC neuronal activity were characterized. In haloth-aneanesthetized rats, intracerebroventricular administration of CRF was found to have two distinct actions: A dose-dependent increase in spontaneous discharge activity was observed 3 min after peptide injection, with 1.0 and 3.0 micrograms CRF increasing activity by 7 +/- 2 and 47 +/- 12%, respectively; Ala14CRF (3.0 micrograms), an inactive analogue of CRF, had no effect on LC spontaneous discharge rates. These results confirm and extend previous studies of CRF activation of LC basal discharge activity; additionally, CRF (1.0 and 3.0 micrograms) disrupted sensory responses of LC cells to sciatic nerve stimulation. As previously reported, responses of LC neurons to electrical stimulation of the sciatic nerve usually consisted of a brief activation beginning 20-40 ms after stimulus followed by a period of relatively suppressed activity lasting 100-200 ms. CRF attenuated both components. Responses plotted as normalized, cumulative histograms became more linear in the presence of CRF (1.0 and 3.0 micrograms), suggesting that discharge rates during phasic responses to sciatic stimulation were similar to spontaneous rates. Statistical comparison using the Kolmogorov-Smirnoff test or correlation coefficients demonstrated that both 1.0 and 3.0 micrograms CRF reduced response components, while 0.3 micrograms and Ala14CRF (3.0 micrograms) had no effect. The degree of attenuation of LC sensory responses by CRF was not linearly related to the magnitude of CRF-induced increases in spontaneous discharge rate, suggesting that these are distinct effects of CRF.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

The distribution of tyrosine hydroxylase-immunoreactive fibers in primate neocortex is widespread but regionally specific.

An antiserum directed against tyrosine hydroxylase (TH), an enzyme involved in dopamine and norepinephrine synthesis, was used to visualize axons immunohistochemically in monkey neocortex. Labeled fibers were distributed throughout the entire neocortex, but they had striking patterns of regional and laminar specialization. For example, primary motor cortex contained the greatest density of TH-labeled fibers, whereas primary sensory regions were sparsely innervated. Marked heterogeneity of fiber density was also present among the association regions of the frontal, parietal, and temporal lobes. In addition, the laminar pattern of innervation in a given region was correlated with its fiber density. Sparsely innervated regions had labeled fibers only in layer I and sometimes layer VI. In regions of intermediate density, labeled fibers tended to be located in layers I-superficial III and layers V-VI, whereas in densely innervated motor cortex TH-immunoreactive fibers were present in all cortical layers. Comparison of these distribution patterns with those produced by an antiserum directed against dopamine-beta-hydroxylase (DBH), a specific marker of neocortical noradrenergic axons, revealed marked differences. DBH-immunoreactive fibers were observed in some cortical locations where few or no TH-labeled fibers were present. In other regions, the density of TH-immunoreactive processes far exceeded that of DBH-labeled fibers. These findings indicate that nearly all of the immunoreactive fibers revealed by this anti-TH antiserum are dopaminergic. This interpretation was further supported by lesions of the ascending noradrenergic fibers in the brain stem, which reduced DBH immunoreactivity, but not TH immunoreactivity, in neocortex. The distinctive innervation patterns of TH-immunoreactive fibers suggest a functional specialization of the dopaminergic projections to primate neocortex.

Animals↗
PubMed1986

Noradrenergic and serotoninergic innervation of cortical, thalamic, and tectal visual structures in Old and New World monkeys.

Antisera directed against human dopamine-beta-hydroxylase and against serotonin were used to characterize the noradrenergic (NA) and serotoninergic (5-HT) innervation of several cortical and subcortical visual areas in squirrel monkey (Saimiri sciureus) and cynomolgus monkey (Macaca fascicularis). Few species differences were observed for either monoamine. Cortical areas 17 and 18, as well as visual areas in the temporal and parietal lobe were found to exhibit regional specialization of both 5-HT and NA innervation. Precisely at the border between areas 17 and 18, the laminar innervation patterns and density characteristic of NA fibers in area 17 (Morrison et al., '82a; Kosofsky et al., '84) shift so that layer IV of area 18 contains more fibers than layer IV of area 17, and the overall density of fibers in area 18 is higher. For 5-HT, the highly laminated patterns characteristic of area 17 (Morrison et al., '82a; Kosofsky et al., '84) also observe this cytoarchitectonic boundary. Fibers in area 18 are more evenly distributed across laminae, and the overall density of fibers decreases. The visual region of the inferotemporal cortex was found to be very lightly innervated by NA fibers and very densely innervated by 5-HT fibers. Area 7 of the parietal lobule was more densely innervated by NA fibers, and less densely innervated by 5-HT fibers, than any other visual cortical region examined. The visual thalamic nuclei exhibited even greater regional differences in the density of NA innervation. The lateral geniculate nucleus was found to be virtually devoid of NA fibers, while the pulvinar-lateral posterior complex was densely innervated. The density of 5-HT fibers was more uniform across thalamic visual nuclei. The lateral geniculate, pulvinar, and lateral posterior nuclei all exhibit a moderate to high density of immunoreactive fibers. In the mesencephalon, the superficial layers of the superior colliculus were found to be densely innervated by NA fibers, whereas 5-HT fibers were most dense in the intermediate layers. These patterns of innervation indicate that, in these primate species, functionally related visual regions share common and distinguishable densities of NA innervation. Specifically, tecto-pulvinar-juxtastriate structures are more densely innervated than geniculo-striate and inferotemporal structures. These relationships suggest that, within the visual system, NA fibers preferentially innervate the regions involved in spatial analysis and visuomotor response rather than those involved in feature extraction and pattern analysis.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Efferent projections of nucleus locus coeruleus: topographic organization of cells of origin demonstrated by three-dimensional reconstruction.

The present study examines the spatial distribution within rat locus coeruleus of neurons projecting to particular brain regions. In order to accurately recreate, in digital and pictorial formats, the spatial distribution of neurons for the entire nucleus locus coeruleus, three-dimensional reconstructions were created which specified the location of each individual Nissl-stained locus coeruleus cell in each of five nuclei. Dynamic computerized displays were visually analyzed and statistically compared. The nuclei from different brains were found to be strikingly similar in density and distribution of cells. In order to determine whether the cells of origin for particular locus coeruleus projections were clustered within the nucleus, reconstructions were created of the distributions of cells labeled by injections of a retrograde tracer, horseradish peroxidase, into particular terminal regions. Groups consisting of animals with injections into the same target areas were visually and statistically compared. The cells of origin of most efferent projections were found to be spatially organized within locus coeruleus. Specifically, projections to both the dorsal and ventral hippocampus originated solely from the dorsal segment of the nucleus, while spinal cord projections originated from ventral-posterior locus coeruleus. Cells of origin of cerebral and cerebellar cortical efferents, as well as hypothalamic efferents, exhibited less clustering, although reliable differences in distribution were observed. The most striking example of clustered cells of origin was exhibited by the large norepinephrine-containing cells constituting the anterior pole of locus coeruleus which were labeled only by hypothalamic injections. This analysis of spatial organization within locus coeruleus is unique in its utilization of a defined control group, experimental groups consisting of strictly defined replications, accurate three-dimensional reconstruction, and statistical comparisons. The demonstrated spatial heterogeneity of locus coeruleus neurons with respect to efferent projections can now be compared to the spatial distributions of other cellular characteristics such as soma morphology, colocalized transmitters and physiological properties. Presumably, such spatial segregation reflects the operation of functionally important organizing principles within the nucleus.

Animals↗
PubMed1986

Efferent projections of nucleus locus coeruleus: morphologic subpopulations have different efferent targets.

This study quantitatively addresses the hypothesis that there is a systematic relationship between the morphologic characteristics of locus neurons and the particular target regions they innervate. Following horseradish peroxidase injections into selected terminal fields, locus coeruleus cell bodies are heavily labeled by retrograde transport so that somata size and shape, and in many cases primary dendritic pattern can be observed. This allows the classification of neurons as one of six cell types: large multipolar cells within ventral locus coeruleus, large multipolar cells in the anterior pole of locus coeruleus, fusiform cells in dorsal LC, posterior pole cells, medium-sized multipolar cells (termed core cells in this report), and small round cells. It was found that while core cells contribute to the innervation of all terminal fields examined, other cell types project to more restricted sets of targets. The contributions of each type to selected efferents are presented in detail. In particular, fusiform cells project to hippocampus and cortex, large multipolar cells in ventral locus coeruleus project to spinal cord and cerebellum, and small round cells in central and anterior locus coeruleus, as well as large multipolar cells in anterior locus coeruleus, project to hypothalamus. These results, in conjunction with those described in the preceding report, indicate that locus coeruleus is intrinsically organized with respect to efferent projections with much more specificity than has previously been evident. This high degree of organization is consistent with other recent demonstrations of functional specificity exhibited by locus coeruleus neurons.

Animals↗
PubMed1986

The monoaminergic innervation of primate neocortex.

In brain, the monoamines, dopamine, norepinephrine, and serotonin, are confined to anatomically distinct neuronal systems, each of which furnishes widespread projections to neocortex. In primate, but not in rat, the terminal patterns of each of these systems have a high degree of regional and laminar specificity. These findings suggest that there are different sites of action and possibly different functional roles for each of the monoamines. This type of precise anatomic information is essential to our understanding of the possible involvement of monoamines in human disease states.

Animals↗
PubMed1985

Impulse conduction properties of noradrenergic locus coeruleus axons projecting to monkey cerebrocortex.

Antidromically driven action potentials were recorded from norepinephrine-containing locus coeruleus neurons in response to electrical stimulation of cerebrocortical and thalamic areas in anesthetized squirrel monkeys. These cells reliably conducted impulses from cortical sites of distances up to 100 mm from locus coeruleus. Monkey locus coeruleus neurons were found to exhibit several properties previously described for these cells in rat, including slow spontaneous discharge rates, characteristic impulse waveforms, antidromic activation from many target areas, a period of suppressed activity following either antidromic or orthodromic driving and responsiveness to noxious stimuli presented as subcutaneous electrical stimulation of a rear foot. However, a large population of monkey locus coeruleus neurons was found to exhibit more rapid conduction velocities than previously found for rat (e.g. approximately 34% were greater than 1 m/s), resulting in similar conduction latencies to distant target areas in the two species. This indicates that the conduction times required for locus coeruleus impulses to reach distant target areas may be conserved across different species and sizes of brains, suggesting that these latencies play an important role in the general function of the locus coeruleus system in brain and behavioral processes.

Animals↗
PubMed1984

The serotonin and norepinephrine innervation of primary visual cortex in the cynomolgus monkey (Macaca fascicularis).

The morphology and laminar distribution of norepinephrine (NE) and serotonin (5-hydroxytryptamine, 5-HT) axons in the primary visual cortex of cynomolgus monkeys (Macaca fascicularis) have been analyzed by immunocytochemistry with antibodies directed against dopamine-beta-hydroxylase (DBH) and against 5-HT. The NE and 5-HT innervation of primary visual cortex (area 17) in the monkey exhibit highly differentiated laminar patterns. Both of these monoamine axonal systems form tangentially continuous laminar bands that differ in density, morphology, and predominant orientation of constituent fibers. Serotonin axons, present in all cortical layers, form two especially prominent, dense bands of arborizing fibers; one extending from midlayer III through IVC-alpha and the other from VA through VI. NE axons within cynomolgus visual cortex are markedly less dense than 5-HT axons, and laminar differences in NE density are less prominent. NE axons form two broad bands of moderate density extending through deep and superficial cortical layers, separated by layer IVC, which is conspicuously poor in NE fibers. The laminar complementarity of 5-HT and NE innervation that is a notable feature of the squirrel monkey visual cortex is not present in cynomolgus monkey; in this Old World monkey NE and 5-HT axons show considerable overlap such that the same cortical layers appear to be innervated by both neurotransmitters. By virtue of their laminar distribution, 5-HT and NE axons may each have a selective influence on the intrinsic circuitry of primate cerebral cortex, and, for 5-HT in particular, the specific cellular targets of this influence are likely to differ in New and Old World monkeys.

Animals↗
PubMed1984

Auditory event-related potentials in the squirrel monkey: parallels to human late wave responses.

Event-related potentials (ERPs) were recorded from the brain surface in squirrel monkeys during the presentation of two auditory stimulus paradigms which have previously been utilized to elicit scalp-recorded ERPs in humans. In the first paradigm, inter-stimulus interval (ISI) was systematically varied during the presentation of a series of tone pips. The tones produced a negative (70 ms)-positive (130 ms) sequence of components similar in morphology to the human scalp-recorded N1-P2 'vertex' potential. The amplitude of the N70 and P130 components recorded from midline electrodes decreased with decreasing ISI, as previously shown for the human vertex potential. However, this amplitude change with ISI was not observed in ERPs recorded from lateral frontal and temporal electrodes. These results agree with previous studies of monkeys and humans which suggest at least two different sources contribute to N1-P2 components recorded in response to tones. The effects of stimulus probability and novelty on ERP morphology and amplitude were studied in the second paradigm. ERPs elicited by frequent (P = 0.92) and infrequent (P = 0.08) tone pips presented in an unpredictable order were compared. N70 - P130 components were produced by both stimuli, and the infrequent stimuli also elicited a broad, long latency (300 ms) positive complex that decreased in amplitude with repeated presentations. In humans the same infrequent auditory stimuli produce a frontally distributed late positive component that has been interpreted as indicating the activation of orientation mechanisms or of a 'mismatch detector'. These data suggest that in these paradigms squirrel monkeys exhibit ERPs which are similar in several respects to ERPs recorded to identical stimuli in humans.

Animals↗
PubMed1984

Postnatal development of laminar innervation patterns by monoaminergic fibers in monkey (Macaca fascicularis) primary visual cortex.

Immunohistochemical methods are used to characterize the distribution of noradrenergic and serotonergic fibers in primary visual cortex of cynomolgus monkeys (Macaca fascicularis) at various postnatal ages. Previous studies in adult squirrel monkeys have shown that serotonergic fibers are generally restricted to the upper four cortical laminae and are especially dense in layer IV, whereas noradrenergic fibers are especially dense in layers V and VI, moderate in layers I, II, and III, and virtually absent in layer IV (Morrison, J. H., S. L. Foote, M. E. Molliver, F. E. Bloom, and H. G. W. Lidov (1982) Proc. Natl. Acad. Sci. U.S.A. 2401-2405; Morrison, J. H., S. L. Foote, D. O'Connor, and F. E. Bloom (1982) Brain Res. Bull. 9: 309-319). Since these monoamines, especially norepinephrine, have been hypothesized to play an essential role in the developmental plasticity of visual cortex organization (e.g., Kasamatsu, T., and J. D. Pettigrew (1976) Science 194: 206-209; Pettigrew, J. D., and T. Kasamatsu (1978) Nature 271: 761-763), the present study examined the postnatal development of these innervation patterns, especially just before and just after the reported "critical period" for visual plasticity. A dense serotonergic innervation of layer IV is present at birth along with sparse innervation of other laminae. The adult pattern of serotonergic innervation, which is similar to that in the squirrel monkey but even more specifically laminated, becomes evident by 6 weeks of age. In the adult pattern, the most dense innervation remains in layers IVb and IVc. A much lower density of noradrenergic than of serotonergic fibers is evident at all ages examined. As with serotonin, the lowest density of fibers is observed at birth. By about 2 months of age these noradrenergic fibers have become more dense, and their laminar distribution is similar to that of adult cynomolgus which is similar to adult squirrel monkey. These studies indicate that: (1) both types of innervation display a continuum of development, with no abrupt changes, (2) serotonergic innervation is more dense than noradrenergic innervation at every age examined, (3) these two transmitter systems exhibit very different laminar innervation patterns as early as birth, and (4) the greater laminar specialization of area 17 in cynomolgus versus squirrel monkeys is accompanied by corresponding enhanced laminar specialization of these monoaminergic afferents.

Aging↗
PubMed1983

Physiological properties of ascending locus coeruleus axons in the squirrel monkey.

Discharge activity was recorded extracellularly from individual neurons of the nucleus locus coeruleus in anesthetized squirrel monkeys. These cells exhibited long-duration (2-3 ms) action potentials and discharged spontaneously in a slow (0.2-2 Hz) irregular fashion. Stimulation of the lateral hypothalamus evoked antidromic responses at latencies of 10-20 ms, indicating conduction velocities of over 1 m/s in some cases. The mean refractory period for these axons was 2.6 ms. When the rate of hypothalamic stimulation was increased from 1 to 10 Hz there was a 15-20% increase in antidromic latencies. These properties are similar to those previously observed for rat LC neurons, except that conduction velocities are higher in monkey.

Animals↗
PubMed1983

Loss of pigmented dopamine-beta-hydroxylase positive cells from locus coeruleus in senile dementia of Alzheimer's type.

Serial sections of human brainstem were used to determine the total number of pigmented cells in locus coeruleus and, by immunohistochemical staining using an antiserum directed against human dopamine-beta-hydroxylase (DBH), the number of DBH-positive cells. In 12 brains from elderly control and dementia subjects there wer not significant differences in the total cell populations determined in the same brain by the two techniques. In 6 patients with senile dementia of Alzheimer's type there was a variable loss (average about 60% reduction) in locus coeruleus cells when compared to controls of similar age. The loss of noradrenergic neurones from locus coeruleus was accompanied by an average reduction of similar magnitude in noradrenaline concentration in temporal cortex, with no change or an increase in dopamine content. There was also a significant reduction in the cholinergic marker choline acetyltransferase in cortex samples from the dementia cases.

Aged↗
PubMed1983

Corticotropin-releasing factor activates noradrenergic neurons of the locus coeruleus.

Corticotropin-releasing factor (CRF) administered intraventricularly (0.5 nmol) was found to increase the discharge rates of locus coeruleus (LC) neurons in anesthetized rats. A similar effect on discharge rate was also observed during direct application of CRF to LC neurons by pressure microapplication. Intraventricular administration of CRF-OH, previously demonstrated to be considerably less potent in releasing ACTH, did not alter LC firing rates. These data suggest that activation of these central noradrenergic neurons may constitute an integral part of the overall 'stress response' initiated by CRF release.

Adrenergic Fibers↗