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Biomedical subjects

B L Jacobs

Publications and source records attributed to B L Jacobs.

At least 109 records · Page 6Linked to original sources
PubMed1986

Single unit activity of noradrenergic neurons in locus coeruleus and serotonergic neurons in the nucleus raphe dorsalis of freely moving cats in relation to the cardiac cycle.

Single unit activity of serotonergic (5-HT) neurons in the nucleus raphe dorsalis (NRD) and of noradrenergic (NE) neurons in the locus coeruleus (LC) was recorded in relation to the cardiac cycle in awake, freely moving cats. The discharge of NRD-5-HT neurons showed no relationship to the cardiac cycle, while LC-NE neurons displayed a cardiac periodicity such that the units were most likely to fire from 80 to 180 ms after the peak of the cardiac r-wave (diastole), and least likely to fire during the period from 40 ms before to 60 ms after the r-wave (systole). The strength of this periodicity was inversely related to the discharge rate of individual cells. Exposure to a noxious environmental stimulus (15 min of 100 dB white noise) greatly attenuated the cardiac relationship of LC-NE neurons. A blood volume expansion of approximately 15% (9.0 ml/kg b. wt.) decreased unit rate by about 25%, but did not alter either the timing or the magnitude of the LC-NE cardiac relationship. These data are discussed in terms of the participation of NRD-5-HT and LC-NE neurons in cardiovascular function, and the possible role of LC-NE neurons in short- and long-term volume homeostasis.

Action Potentials↗
PubMed1986

Single unit activity of locus coeruleus neurons in the freely moving cat. I. During naturalistic behaviors and in response to simple and complex stimuli.

The single unit activity of presumed noradrenergic (NE) neurons in the area of the locus coeruleus (LC) was recorded in freely moving cats. Consistent with previous reports, the activity of LC neurons was found to be state dependent: active waking greater than quiet waking greater than slow wave sleep greater than REM sleep (virtually silent). The activity of these neurons showed no relationship to movement per se. In response to simple sensory stimulation, LC units showed a short latency, short duration excitatory response. In response to a variety of non-noxious naturalistic stimuli, e.g. rats, food and a conspecific, LC unit activity did not increase above an active waking baseline. However, in response to noxious stimuli, e.g. pinches, visual threats, emesis, and forced treadmill running, LC unit activity increased above that during active waking and reached its highest levels. These data, in conjunction with those in the following report, are consistent with a general role for NE-LC neurons in the organism's adaptive response to environmental and physiological challenges.

Action Potentials↗
PubMed1986

Single unit activity of locus coeruleus neurons in the freely moving cat. II. Conditioning and pharmacologic studies.

A series of experiments were carried out in which the single unit activity of presumed noradrenergic (NE) neurons in the area of the locus coeruleus (LC) was examined in freely moving cats during two conditioning paradigms and in response to pharmacologic manipulations relevant to anxiety. LC unit activity was examined during conditioned emotional response (CER) and conditioned food reward (CFR) training. During CER training, LC units showed a large increase in activity in response to a stimulus paired with a noxious air puff, whereas no increase in unit activity was seen in response to a stimulus not paired with the air puff (both comparisons relative to their appropriate control conditions). By contrast, during CFR training, a stimulus paired with a rewarding food delivery did not elicit a significant increase in LC unit activity relative to its appropriate control condition. Therefore, NE units in the LC greatly increase their activity in response to a stimulus that predicts the occurrence of a noxious event, but not in response to a stimulus that predicts the occurrence of a rewarding event. Administration of the anxiolytic drug diazepam (0.25 and 2.0 mg/kg, i.p.) had no significant effect on the spontaneous activity of LC neurons, but significantly reduced the excitatory response of LC neurons to simple stimuli. Administration of the anxiogenic drug yohimbine (2.0 mg/kg, i.p.) significantly increased the spontaneous activity of LC neurons. These results support the hypothesis that LC neurons play a role in aversive but not appetitive conditioning, and are consistent with the hypothesis that these neurons may play a role in anxiety. These data are discussed within the broader context of LC neurons mediating the organism's adaptive response to environmental or physiological challenges.

Acoustic Stimulation↗
PubMed1986

Single unit response of noradrenergic, serotonergic and dopaminergic neurons in freely moving cats to simple sensory stimuli.

The response of noradrenergic (NE), serotonergic (5-HT), and dopaminergic (DA), neurons to repeated presentations (once/2 s for 64 trials) of phasic auditory (click) and visual (flash) stimuli was examined in freely moving cats. All 3 groups of neurons displayed similar response latencies and somewhat similar durations of excitation to both stimulus modalities. 5-HT neurons in the mesencephalic raphe nuclei showed no decrease in responsiveness across trials to either of the stimuli. DA neurons in the substantia nigra displayed no decrease in responsiveness across trials to the auditory stimulus, but did display an approximately 50% decrease in response to the visual stimulus. NE neurons in the locus coeruleus showed an approximately 50% decrease in responsiveness to both the auditory and visual stimuli. These data are consistent with previous studies showing that the response of many neurons in the brainstem reticular formation habituates to the repetitive presentation of sensory stimuli. They also show that the response of reticular formation neurons are heterogeneous and that they can be subdivided on the basis of their neurochemical identity. Finally, these data provide support for the involvement of NE neurons, and to a lesser extent DA neurons, in various forms of behavioral plasticity.

Animals↗
PubMed1985

Substantia nigra dopaminergic unit activity in behaving cats: effect of arousal on spontaneous discharge and sensory evoked activity.

Single-unit activity of dopaminergic neurons in the substantia nigra was recorded in freely moving cats during a variety of conditions designed to shed light on the hypotheses that these neurons are involved in the regulation of arousal-stress and/or selective attention. Both aversive and non-aversive arousing experimental conditions were used, including tail pinch, immersion of feet in ice-water, white noise, inaccessible food, feeding, grooming, inaccessible rats, and somatosensory stimulation. None of these conditions had an effect on tonic neuronal discharge rate. However, these neurons did exhibit brief excitatory and inhibitory responses to phasic auditory or visual stimuli presented when the cat was sitting quietly. These responses were dramatically attenuated if these stimuli were presented during the aforementioned conditions of behavioral arousal. This sharply contrasts with the inability of these same conditions to influence spontaneous discharge rate. The sensitivity of this neuronal sensory response to the concurrent behavioral condition supports the hypothesis that these neurons are involved in attentional processes or selective responding. The lack of responsiveness of these neurons to a variety of arousal/stress manipulations supports the hypothesis that dopaminergic neurons play a permissive, rather than an active, role in these processes.

Acoustic Stimulation↗
PubMed1985

Dopaminergic modulation of sensory responses of striatal neurons: single unit studies.

The extracellular single unit responses of striatal neurons to repetitive stimulation of the sciatic nerve were recorded in the urethane anesthetized rat. Changes in the magnitude of these responses after pharmacological manipulation of dopamine (DA) neurotransmission were evaluated. While the intravenous administration of 0.25 mg/kg i.v. amphetamine (AMPH) had no significant effect on baseline firing rates as compared to saline controls, the magnitudes of excitatory and inhibitory evoked single unit responses were significantly decreased by 68% by AMPH. Further, this reduction in response magnitude produced by AMPH was completely blocked by pretreatment with 0.5 mg/kg i.v. haloperidol or by intrastriatal 6-hydroxydopamine lesions. This indicates that the observed effect is mediated by dopamine located in nerve terminals within the striatum. These results suggest that DA functions to modulate the responsiveness of striatal neurons to afferent signals.

Animals↗
PubMed1985

Serotonin turnover in raphe neurons transplanted into rat hippocampus.

Injections of the neurotoxin, 5,7-dihydroxytryptamine, into rostral raphe nuclei in rats reduced serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in hippocampus to 35-50% of normal levels but only reduced 5-HT synthesis and catabolism by 20-35%. The small reduction in 5-HT metabolism as compared to depletion of 5-HT suggests that 5-HT turnover was increased in nerve terminals that survived the neurotoxin lesion. Transplantation of rat fetal raphe cells into the 5-HT-denervated hippocampus restored 5-HT and 5-HIAA levels and 5-HT synthesis to 125-150% of normal. This demonstrates that transplantation of fetal raphe tissue can restore metabolism to normal levels in the 5-HT denervated hippocampus.

5,7-Dihydroxytryptamine↗
PubMed1985

Locus coeruleus unit activity in freely moving cats is increased following systemic morphine administration.

Contrary to previous reports of morphine's depression of locus coeruleus (LC) unit activity in anesthetized animals, acute administration of morphine (0.5, 2.0 or 4.0 mg/kg, i.p.) did not decrease the unit activity of noradrenergic neurons in the area of the LC of freely moving cats. In fact at the higher doses examined (2.0 and 4.0 mg/kg) morphine significantly increased unit activity. Naloxone (1 mg/kg, i.p.) administration reversed the increase in unit activity produced by morphine. When these same studies were conducted in cats first anesthetized with chloral hydrate, morphine produced a significant decrease in unit activity in a naloxone-reversible manner. These results suggest that previous reports of systemic morphine's depression of LC unit activity may be at least partially attributable to an interaction with anesthesia. Morphine's multiplicity of actions upon the LC is discussed.

Adrenergic Fibers↗
PubMed1985

Caudate unit activity in freely moving cats: effects of phasic auditory and visual stimuli.

Quantitative analyses of the single unit responses to sensory stimuli were made in caudate nucleus neurons in the unanesthetized freely moving cat. Over half of the cells were responsive to repetitive presentation of simple sensory stimuli. Typically, neurons gave similar responses to both auditory (click) and visual (flash) stimuli. This study confirms previous reports of the polysensory response characteristics of caudate nucleus neurons, and extends these observations to the freely moving animal.

Animals↗
PubMed1985

Activity of serotonin-containing neurons in nucleus raphe magnus in freely moving cats.

Serotonergic neurons were recorded in the nucleus raphe magnus in freely moving cats and were initially identified on-line by their characteristic slow and regular spontaneous activity during quiet waking (3.42 +/- 0.33 spikes/s; mean +/- SE). Discharge rates of these serotonergic neurons were highest during active waking (4.49 +/- 0.40 spikes/s), intermediate during slow-wave sleep (middle: 2.14 +/- 0.23 spikes/s), and lowest during REM sleep (0.20 +/- 0.03 spikes/s). Although these cells fired at a rate 31.3% higher during active waking than during quiet waking, their activity displayed no correlation with phasic elevations of the nuchal EMG or overt body movements. In addition, no relationship was observed between the activity of these neurons during slow-wave sleep and the occurrence of sleep spindles in the cortical EEG or pontogeniculooccipital waves recorded from the lateral geniculate nucleus. Serotonergic neurons of nucleus raphe magnus were also relatively unresponsive to phasic auditory and visual stimuli, with about half of the cells examined showing weak excitatory responses. These neurons did respond, however, to the administration of a small dose of the serotonin specific agonist, 5-methoxy-N,N-dimethyltryptamine (250 micrograms/kg, i.m.) with a mean decrease in unit activity of 73.6 +/- 4.5%. The results of this study are compared with those previously reported for serotonergic neurons in the dorsal raphe nucleus, nucleus centralis superior, and nucleus raphe pallidus of freely moving cats.

Acoustic Stimulation↗
PubMed1985

Response of serotonin-containing neurons in nucleus raphe magnus to morphine, noxious stimuli, and periaqueductal gray stimulation in freely moving cats.

Extracellular single-unit recordings were made in nucleus raphe magnus in unanesthetized, unrestrained cats. Discharge of serotonergic neurons in this region was increased when animals were aroused by noxious stimuli such as pinch and radiant heating of the tail, but these cells were not specifically nociceptive. Peristimulus time histograms indicated that stimulation in the periaqueductal gray was excitatory but alveolar nerve stimulation at a noxious current intensity was no more effective than nonnoxious nerve stimulation in activating serotonergic unit discharge: Similarly, stressful treatments such as physical restraint increased the discharge of some serotonergic neurons, but these cells were activated during any period of behavioral arousal whether or not arousal was the result of aversive treatment. Injection of Formalin into the paw produced pain lasting about 30 min without increasing serotonergic unit discharge above rates observed during undisturbed active waking behavior. The activity of serotonergic neurons was not increased by an analgesic dose of morphine (2 mg/kg, i.p.). These results then are not consistent with the hypothesis that morphine analgesia depends on activation of serotonergic neurons in nucleus raphe magnus or that these cells are specifically involved in modulation of nociception. These neurons may, however, be involved in nociceptive control within the context of a general modulation of sensorimotor processes by serotonin in the central nervous system. We did observe neurochemically unidentified neurons in the medulla whose discharge was more specifically activated by aversive stimuli and also by morphine. It is possible that these neurons are more directly involved in the mediation of opiate and/or stress-induced analgesia.

Analgesia↗
PubMed1985

Biosynthesis of reovirus-specified polypeptides: the reovirus s1 mRNA encodes two primary translation products.

Reovirus serotypes 1 (Lang strain) and 3 (Dearing strain) code for a hitherto unrecognized low-molecular-weight polypeptide of Mr approximately 12,000. This polypeptide (p12) was synthesized in vitro in L-cell-free protein synthesizing systems programmed with either reovirus serotype 1 mRNA, reovirus serotype 3 mRNA, or with denatured reovirus genome double-stranded RNA, and in vivo in L-cell cultures infected with either reovirus serotype. The synthesis of p12 in vivo was insensitive to actinomycin D, and occurred at similar times after infection as the previously identified reovirus encoded lambda, mu, and sigma polypeptides. Pulse-chase experiments in vivo, and the relative kinetics of synthesis of p12 in vitro, indicate that it is a primary translation product. Fractionation of reovirus mRNAs by velocity sedimentation and translation of separated mRNAs in vitro suggests that p12 is coded for by the s1 mRNA, which also codes for the previously recognized sigma 1 polypeptide. Synthesis of both p12 and sigma 1 in vitro in L-cell-free protein synthesizing systems programmed with denatured reovirus genome double-stranded RNA also suggests that these two polypeptides can be coded by the same mRNA species. The Mr approximately 12,000 polypeptide was not a detectable structural component of purified virions, and antiserum prepared against purified reovirions did not immunoprecipitate p12. It is proposed that the Mr approximately 12,000 polypeptide encoded by the S1 genome segment be designated sigma 1bNS, and that the polypeptide previously designated sigma 1 be renamed sigma 1a.

Animals↗
PubMed1985

Biosynthesis of reovirus-specified polypeptides. The s1 mRNA synthesized in vivo is structurally and functionally indistinguishable from in vitro-synthesized s1 mRNA and encodes two polypeptides, sigma 1a and sigma 1bNS.

The structural and functional properties of the reovirus serotype 1 (Lang strain) s1 mRNA were examined. Reovirus s-class mRNAs, synthesized either in vivo within infected mouse L cells or in vitro by chymotrypsin-derived cores of purified virions, were purified by filter-hybridization using cDNA clones of the S-class genome segments. S1 cDNA-selected mRNA encoded the synthesis of the Mr approximately 12,000 nonstructural polypeptide designated sigma 1bNS in addition to the well-established structural polypeptide sigma 1, now designated sigma 1a. The coding properties of in vivo- and in vitro-synthesized s1 mRNA were equivalent: both encoded sigma 1a and sigma 1bNS. Primer extension analysis of s1 mRNA revealed a single major 5' terminus for both in vivo- and in vitro-synthesized s1 mRNA. These results suggest that there is a single transcript of the reovirus S1 genome segment which is functionally dicistronic, and likely encodes both sigma 1a and sigma 1bNS.

Animals↗
PubMed1985

Noradrenergic modulation of sensorimotor processes in intact rats: the masseteric reflex as a model system.

The masseteric jaw closure reflex was utilized as a model system with which to gauge the functional activity of central noradrenergic neurons. This system was chosen because it is a simple monosynaptic reflex the neuronal substrate of which receives a dense noradrenergic input. The modulatory effects of norepinephrine (NE) on this response in the intact, chloral hydrate-anesthetized rat were studied with a variety of pharmacological strategies. Initially, a reflex facilitation was obtained with the catecholamine precursor L-DOPA. Manipulations with greater specificity of action on the noradrenergic system were then employed. First, we used the presynaptic alpha-2 noradrenergic agonist clonidine, which acts to decrease noradrenergic transmission. Clonidine attenuated the amplitude of the reflex, and this suppression was blocked by pretreatment with the alpha-2 antagonist yohimbine. The effects of yohimbine itself were then examined, and a biphasic effect was obtained. At low doses, at which it preferentially acts as an antagonist at presynaptic alpha-2 receptors and increases noradrenergic transmission, yohimbine enhanced the reflex. At higher doses, at which it also displays postsynaptic alpha-1 antagonist activity, yohimbine depressed the reflex. This reflex modulation by yohimbine was blocked by pretreatment with the alpha-1 antagonist prazosin. The anatomical site of the observed effect was then localized to the direct noradrenergic innervation of the reflex circuitry by locally destroying, with 6-hydroxydopamine, the noradrenergic terminals in the trigeminal motor nucleus mediating the response. This significantly attenuated the reflex modulation by yohimbine, without affecting elicitation of the reflex itself.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Some behavioral effects of hallucinogens are mediated by a postsynaptic serotonergic action: evidence from single unit studies in freely moving cats.

Although central serotonergic systems appear to be linked importantly to the mechanism of action of a variety of hallucinogenic drugs, the nature of this interaction has remained unclear. In the present study, the question of whether the critical link is presynaptic or postsynaptic was examined in cats. Behaviorally inactive doses (1.0 mg/kg) of the serotonin receptor antagonists mianserin, ketanserin or metergoline effectively blocked behavior, as measured by the cat limb flick response, elicited by either LSD (50 micrograms/kg) or DOM (250 micrograms/kg) but not that resulting either from lisuride (50 micrograms/kg) or a high dose of apomorphine (4 mg/kg). Pretreatment with 1.0 mg/kg of mianserin, which completely attenuated LSD's behavioral effect, failed to alter LSD-induced depression of mesencephalic serotonergic neuron discharge. These results demonstrate that at least some of the behavioral effects of LSD can be blocked by pharmacological antagonism of postsynaptic serotonin receptors which leaves LSD's presynaptic effect unaffected. Thus, the behavioral, and possibly psychoactive, effects of hallucinogens appear to be attributable to an action at 5HT2 receptors, presumably located postsynaptically.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗