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Biomedical subjects

F E Bloom

Publications and source records attributed to F E Bloom.

At least 307 records · Page 17Linked to original sources
PubMed1981

Electrophysiologic assessment of receptor changes following chronic drug treatment.

Electrophysiological techniques offer a direct cellular approach to questions of neurotransmitter receptor-drug interaction. Although these methods demand considerable technical expertise and advanced instrumentation, as well as satisfaction of certain biological and pharmacological provisos, they are capable of providing detailed information on the functional status of receptors not readily attained from studies on disrupted cell systems. The development of improved methods for the quantitative comparison of changes in transmitter responsiveness after chronic experimental manipulations now makes possible the application of these electrophysiological approaches to current problems in neuropharmacology. This paper reviews the technical and biological considerations that underlie tha analysis of these problems by electrophysiology and illustrates some of the interpretative pitfalls.

Animals↗
PubMed1981

Activity of norepinephrine-containing locus coeruleus neurons in behaving rats anticipates fluctuations in the sleep-waking cycle.

Spontaneous discharge of norepinephrine-containing locus coeruleus (NE-LC) neurons was examined during the sleep-walking cycle (S-WC) in behaving rats. Single unit and multiple unit extracellular recordings yielded a consistent set of characteristic discharge properties. (1) Tonic discharge co-varied with stages of the S-WC, being highest during waking, lower during slow wave sleep, and virtually absent during paradoxical sleep. (2) Discharge anticipated S-WC stages as well as phasic cortical activity, such as spindles, during slow wave sleep. (3) Discharge decreased within active waking during grooming and sweet water consumption. (4) Bursts of impulses accompanied spontaneous or sensory-evoked interruptions of sleep, grooming, consumption, or other such ongoing behavior. (5) These characteristic discharge properties were topographically homogeneous for recordings throughout the NE-LC. (6) Phasic robust activity was synchronized markedly among neurons in multiple unit populations. (7) Field potentials occurred spontaneously in the NE-LC and were synchronized with bursts of unit activity from the same electrodes. (8) Field potentials became dissociated from unit activity during paradoxical sleep, exhibiting their highest rates in the virtual absence of impulses. These results are generally consistent with previous proposals that the NE-LC system is involved in regulating cortical and behavioral arousal. On the basis of the present data and those described in the following report (Aston-Jones, G., and F. E. Bloom (1981) J. Neurosci.1: 887-900), we conclude that these neurons may mediate a specific function within the general arousal framework. In brief, the NE-LC system may globally bias the responsiveness of target neurons and thereby influence overall behavioral orientation.

Animals↗
PubMed1981

Norepinephrine-containing locus coeruleus neurons in behaving rats exhibit pronounced responses to non-noxious environmental stimuli.

The effect of sensory stimulation on discharge in norepinephrine-containing locus coeruleus (NE-LC) neurons was studied in unanesthetized behaving rats. Single unit and multiple unit extracellular recordings demonstrated consistent patterns of response. (1) Short latency (15-to 50-msec), transient, biphasic changes in discharge were elicited predictably by non-noxious auditory, visual, and somatosensory stimuli; individual recordings typically exhibited polysensory responsiveness. (2) Sensory-evoked field potentials (FPs) were synchronized with unit responses simultaneously recorded from the same electrodes. (3) The magnitudes of sensory-evoked response varied as a function of vigilance, so that the largest responses occurred for stimuli which awakened animals and the least responsiveness was exhibited during uninterrupted sleep. (4) Sensory responsiveness decreased during grooming and sweet water consumption, similar to the results for sleep. (5) Characteristic response properties were topographically homogeneous throughout the NE-LC. (6) Discharge was synchronized markedly among neurons in multiple unit populations during phasic robust responses. These results are interpreted in light of the preceding report (Aston-Jones, G., and F.E. Bloom (1981) J. Neurosci. 1: 876-886) and studies of the postsynaptic effects of NE to indicate that the NE-LC system may function more in phasic processes than in modulation of the tonic arousal level. We propose that pronouced NE-LC discharge may enhance activity within target cell systems primarily concerned with processing salient external stimuli and suppress cental nervous system activity related more to tonic, vegetative functions. Thus, the NE-LC system may bias global behavioral orientation between stimuli in the external versus internal environments.

Animals↗
PubMed1980

Antiserum to nerve growth factor does not prevent the increase of brain stem noradrenaline after neonatal 6-hydroxydopa.

Antiserum to nerve growth factor (anti-NGF) given intraventricularly to newborn rats systemically injected with 6-hydroxydopa (6-OH-DOPA), did not prevent the long-term increase of brain stem noradrenaline produced by 6-OH-DOPA when given alone. Since the anti-NGF was biologically active and penetrated into the brain parenchyma, the role played by NGF in the outgrowth of central noradrenergic neurons, responsible for the elevation of brain stem noradrenaline, does not seem to be important.

Animals↗
PubMed1980

Physiological correlates of ethanol intoxication tolerance, and dependence in rat cerebellar Purkinje cells.

After single injections of ethanol (1-4 g/kg, i.p.), single unit extracellular recordings of rat cerebellar Purkinje cells show dramatically increased frequency of climbing fiber bursts and occasional increases in simple spike firing rate. These effects of ethanol are not observed in rats chronically treated with the substance for 11-14 days: firing patterns 0-3 h after the last ethanol administration do not differ significantly from controls. However, rats chronically treated and then withdrawn from ethanol slow significant, progressive decreases in climbing fiber activity and firing rates from 3 to 32 h after the last ethanol administration. These effects on cerebellar Purkinje cell firing appear to be physiological correlates of the phenomena of ethanol intoxication, tolerance, and dependence.

Alcoholism↗
PubMed1980

Brain aminergic axons exhibit marked variability in conduction velocity.

Impulses in rat locus coeruleus neurons exhibit pronounced conduction latency decreases, followed by even larger latency increases (of over 20 msec in some cases) during a single train of antidromic activation. The magnitude of latency fluctuation varies as a function of basal antidromic latency, frequency of stimulation, and number of stimuli in a train. These and additional data indicate that this variability in latency is a consequence of altered impulse conduction velocity along the axons, perhaps reflecting reduced ion concentration gradients resulting from impulse propagation. These latency changes may allow thin unmyelinated axons to influence target cells most effectively with short bursts of activity, and suggest that myelination and large axon diameter provide for high fidelity as well as for high velocity of impulse flow in nervous tissue.

Animals↗
PubMed1980

Innervation of embryonic rat cerebral cortex by catecholamine-containing fibers.

Catecholamine-containing neuronal processes penetrate to the outer superficial layers of the developing neocortex via the lateral neocortex anlage by embryonic day (ED) 16, only 48 hours after the final cell division of the catecholamine neurons in the mesencephalon and pons-medulla. Sagittal sections were taken from a series of perfused embryos at precise time-intervals after insemination. The corpus striatum receives a large catecholamine input and serves as a reference for tracing the very fine varicose processes that course through the caudate nucleus to innervate the more rostral structures of the developing neocortex cerebri. The input fibers to the neocortex arrive via three to four small fiber bundles, entering chiefly at the ventro-rostral aspect. The bundles than bifurcate into the deep and superficial layers of the cortex. Between ED16 to ED21 the innervation progresses in ventral to dorsal and rostral to caudal directions. Embryonically, fluorescent fibers are observed in the outermost superficial layer and in the intermediate zone, below the cortical plate; only rarely are they seen crossing the cortical plate. The demonstration of monoaminergic neuronal fibers reaching neocortical structures by ED16 adds further weight to the speculation that they may play a role in induction and differentiation, and suggests that post-natal experimental manipulations using ascending-bundle lesions will have been performed at least five days after the arrival of catecholamine fibers at their cortical destinations.

Animals↗
PubMed1980

Opiate receptors influence vasopressin release from nerve terminals in rat neurohypophysis.

A previous report described the existence of substantial amounts of enkephalin immunoreactivity and the occurrence of nerve terminals containing an enkephalin-like material in the pars nervosa of rat pituitary. It was suggested that an enkephalin innervation of the pars nervosa originating from the magnocellular hypothalamic nuclei might regulate the secretion of neurohypophyseal hormones. The results of the present studies support this hypothesis, as we find that a stable enkephalin analogue (D-Ala 2,D-Leu5-enkephalin) inhibits the calcium-dependent release of vasopressin evoked by electrical stimulation of the rat pituitary stalk in vitro. A similar inhibition of the stimulus-evoked vasopressin release is caused by morphine and beta-endorphin, and the inhibitory effects of the enkephalin analogue can be reversed by naloxone. These findings suggest the possible existence of inhibitory opiate receptors on the terminals of vasopressin fibres in the pars nervosa.

Animals↗
PubMed1980

Tetrahydropapaveroline inhibits dopamine uptake in rat brain synaptosomes.

THP, which can be formed by the condensation of dopamine with dopaldehyde, has been proposed to be involved in mediating some of the effects of ethanol on the central nervous system. We have observed that THP induces small granular vesicles (SGVs), visible with the electron microscope, in central dopamine fibers (Koda et al., 1978). In order to investigate the mechanism of SGV induction by THP, we examined dopamine and THP uptake into synaptosomes. [3H]THP (1.25 Ci/mmole), prepared by catalytic exchange labeling, exhibited no active uptake into synaptosomes (kinetics consistent with simple diffusion). THP did exhibit competitive inhibition (Ki = 4.2 x 10(-5) M) of [3H] dopamine uptake (Km = 2.6 x 10(-7) M; Vmax = 8.5 nmoles/min/g pellet) in these preparations. It is unlikely that endogenous THP would accumulate to concentrations sufficiently high to inhibit dopamine uptake under physiological conditions.

Animals↗
PubMed1980

Accurate three-dimensional reconstruction of neuronal distributions in brain: reconstruction of the rat nucleus locus coeruleus.

A technique is described which permits construction of accurate, quantified 3-dimensional maps of the distribution of neuronal cell groups in brain. The cartesian coordinates of landmarks and individual neurons are obtained from serial histological sections utilizing a computer-linked digitizing microscope. The digitized images of these sections are displayed on a computer graphics picture system where they are aligned so that spatial relationships within the nucleus are essentially identical to those of the intact brain. This is accomplished using information about landmarks obtained from photomicrotomy. As a consequence of the alignment procedure, each neuron is assigned a 3-dimensional coordinate representing its position in the reconstituted nucleus, and the reconstruction is oriented in a stereotaxic coordinate system. Nuclei from different brains can then be registered to one another, assigned coordinates relative to this standard coordinate space, and be compared statistically. Differences between nuclei in the spatial distribution of neurons in toto, or in the distribution of anatomically or physiologically defined subpopulations of neurons, can then be visualized with greater accuracy and in more detail than that permitted by traditional techniques. In addition, such comparisons can easily be quantified and statistically evaluated using, for example, analysis-of-variance techniques. For illustrative purposes, the technique is applied to the rat nucleus locus coeruleus as reconstructed from serial Nissl-stained sections.

Animals↗
PubMed1980

Senescent changes in a neurobiological model system: cerebellar Purkinje cell electrophysiology and correlative anatomy.

A within-subjects design was used to assess age changes in cerebellar Purkinje neurons. Four groups of naive male Sprague-Dawley rats, aged 3, 10, 20, and 28 months. underwent single cell recording for electrophysiological assessment of Purkinje cell firing patterns, followed by perfusion for glyoxylic acid induced catecholamine fluorescence. Cerebellar sections were photographed first by fluorescence microscope for catecholamines, and 2-3 weeks later for quantification of lipofuscin autofluorescence. Finally, these same tissues were treated with cresyl violet and photographed a third time to permit quantitative estimates of age changes in the number of Nissl staining Purkinje neurons. Electrophysiological studies revealed significant effect of age on a number of Purkinje cell firing parameters: in particular, increasing numbers of aberrant, very slow-firing cells were encountered in older animals. These cells showed normal climbing fiber mediated burst activity, but spontaneous simple spike firing rates 3-5 times less than normal. Rats exhibiting the highest numbers of such abnormal cells also exhibited the poorest Nissl staining. Conversely, good Nissl staining of Purkinje neurons in an old rat was a reliable predictor of relatively normal Purkinje cell firing. Lipofuscin was found to accumulate measurably in Purkinje neurons by 20 months of age, and to increase significantly thereafter. Deposition of the substance occurred almost exclusively at the apical pole of the soma. Our data suggest, however, that accumulation of lipofuscin in Purkinje neurons, as well as its reported accumulation in the inferior olive, is not a primary cause of electrophysiological dysfunction. There was no apparent age change in glyoxylic acid induced catecholamine fluorescence nor, in separate pharmacological studies, could any senescent alteration in cerebellar catecholamine levels be found.

Aging↗
PubMed1980

Regional distribution of endorphin, Met5-enkephalin and Leu5-enkephalin in the pigeon brain.

The distribution of beta-endorphin and enkephalin in the pigeon forebrain by immunohistochemistry and radioimmunoassay is essentially analogous to mammals. Both endorphin- and enkephalin-reactive fibers have a similar periventricular distribution, but the enkephalin fibers are more extensive and are also found in the paleostriatum, limbic regions and brain stem, pituitary stalk and notably, penetrating the organum vasculosum hypothalami. There was poor correlation between endorphin and enkephalin regional contents by radioimmunoassay. In contrast, a highly significant correlation was observed between Met5-enkephalin and Leu5-enkephalin regional distribution. These data support the view that enkephalin neurons and endorphin neurons are independent central neuronal systems.

Animals↗
PubMed1980

Stress-induced release of prolactin: blockade by dexamethasone and naloxone may indicate beta-endorphin mediation.

Basal levels of immunoreactive (ir) beta-endorphin, corticotropin (ACTH), and prolactin (PRL) in plasma of male rats decrease after dexamethasone pretreatment (400 microgram/kg at 24 hr and 200 microgram/kg at 2 hr before). Inescapable electric footshocks increase ir-beta-endorphin, ACTH, and PRL plasma levels and this effect is blocked by dexamethasone pretreatment. Morphine (20 mg/kg) also increases ir-beta-endorphin, ACTH, and PRL levels. Dexamethasone pretreatment blocks the morphine-induced release of ir-beta-endorphin but does not prevent the morphine-induced release of PRL. Naloxone, the opiate antagonist, decreases basal plasma levels of PRL and partially blocks the stress-induced increase of PRL, but it has no effect on the basal or stress-induced release of ir-beta-endorphin. These results are consistent with the proposal that beta-endorphin may interact with an opiate receptor involved in the regulation of PRL secretion.

Adrenocorticotropic Hormone↗