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B L Jacobs

Publications and source records attributed to B L Jacobs.

At least 91 records · Page 5Linked to original sources
PubMed1990

Noradrenergic modulation of the masseteric reflex in behaving cats. I. Pharmacological studies.

The masseteric (jaw closure) reflex was utilized as a model system for assessing functional changes in central norepinephrine (NE) neurotransmission. This monosynaptic reflex was chosen because of its simple and well-defined circuitry, and because its motor component receives a dense NE innervation. Previous experiments in our laboratory described NE modulation of this reflex in the anesthetized rat. The present experiments examine the effects of NE on this response in the unanesthetized, behaving cat. The masseteric reflex was elicited by electrical stimulation of the mesencephalic trigeminal nucleus, and the response was recorded via electrodes permanently implanted in the masseter muscle. The amplitude of the reflex response was measured before and at various intervals following microinfusion (0.5 microliters) of NE or of various NE agonists directly into the motor trigeminal nucleus (MoV). Microinfusions of NE (0.125-5.0 micrograms) produced dose-dependent increases in the amplitude of the elicited reflex response. These effects were evident within 1 min postinfusion and lasted up to 30 min; in all cases, the response amplitude returned to baseline levels. The increase seen in response to 0.5 micrograms NE was blocked by pretreatment with the alpha-1-adrenergic antagonist prazosin, but not by pretreatment with the serotonin (5-HT) antagonist methysergide. Methysergide did, however, completely block the increase in the amplitude seen in response to microinfusion of 5-HT. Infusion of the alpha-1-adrenergic agonist phenylephrine also increased the amplitude of the reflex response. By contrast, infusion of the beta-adrenergic agonist isoproterenol had no effect, whereas clonidine, a presynaptic alpha-2-adrenergic agonist, decreased its amplitude.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Single-unit responses of serotonergic neurons to glucose and insulin administration in behaving cats.

Extracellular single-unit activity of serotonergic neurons in the dorsal raphe nucleus (DRN) was recorded in response to glucose loading and insulin administration in conscious, freely moving cats. Serotonergic neurons were identified based on their discharge characteristics, activity across states of behavioral arousal, response to systemic administration of serotonin autoreceptor agonists, and histological localization to the DRN. The spontaneous activity of serotonergic neurons varied in association with behavioral state, reaching their highest level during arousal and their lowest level during rapid-eye-movement sleep, when cells typically stopped firing. The activity of serotonergic DRN neurons was not significantly altered by a glucose load (500 mg/kg iv) that produced an approximately 3.5-fold increase in blood glucose levels. Furthermore, serotonergic DRN neuronal activity was not significantly altered after insulin administration (2-4 IU/kg iv), which lowered blood glucose approximately 50% below control levels, or after the rapid reversal of hypoglycemia by subsequent glucose administration. These results indicate that the activity of serotonergic DRN neurons is unrelated to alterations in blood glucose and is not sensitive to elevations of endogenous circulating insulin levels or to exogenous insulin administration. Furthermore, changes in the activity of serotonergic DRN neurons does not appear to be a component of glucoregulatory mechanisms invoked by either hyper- or hypoglycemia. Overall, these results do not support a role for serotonergic DRN neurons in glucoregulation in the cat.

Animals↗
PubMed1988

Microinjected morphine suppresses the activity of locus coeruleus noradrenergic neurons in freely moving cats.

Microinjection of morphine (1.0 microgram/0.1 microliter) produced a significant suppression (approximately 60%) of the single unit activity of locus coeruleus noradrenergic neurons in freely moving cats. This effect was reversible by systemic administration of the opioid receptor antagonist, naloxone (1.0 mg/kg i.v.). The microinjection of naloxone (1.0 microgram/0.1 microliter), however, was without effect on the spontaneous activity of noradrenergic neurons in the locus coeruleus. Non-noradrenergic neurons recorded in the same vicinity showed no consistent response to the microinjection of morphine. These results suggest that the direct effect of opioids in the locus coeruleus is an inhibition of noradrenergic neuronal activity. Furthermore, it appears that opioid influences upon these neurons are not tonically active.

Action Potentials↗
PubMed1988

Systemic naloxone administration potentiates locus coeruleus noradrenergic neuronal activity under stressful but not non-stressful conditions.

When administered during non-stressful, quiet-waking conditions, i.v. naloxone (1.0 mg/kg) had no effect on the activity of locus coeruleus (LC) noradrenergic neurons in behaving cats. In contrast, the activation of LC noradrenergic unit activity produced by restraint stress was greatly potentiated by the same dose of naloxone. Indices of behavioral distress, vocalization and struggling, were also found to be significantly increased in animals given naloxone during stress. These results suggest that endogenous opioids have a moderating influence upon the level of activity of the LC which operates only under specific conditions such as stress.

Animals↗
PubMed1988

Lack of response of serotonergic neurons in the dorsal raphe nucleus of freely moving cats to stressful stimuli.

Changes in brain serotonin (5-HT) neurotransmission have been implicated in the mammalian response to stressful stimuli. The purpose of this study was to examine the extracellular single-unit activity of 5-HT neurons in cats exposed to three stressors: loud (100 dB) white noise, restraint, and confrontation with a dog. Serotonergic neurons were recorded in the dorsal raphe nucleus (DRN) and were identified by (i) slow and regular spontaneous activity, (ii) long duration (approximately 2 ms) waveform, (iii) complete suppression of activity during REM sleep and after systemic administration of 5-methoxy-N-N-dimethyltryptamine (250 micrograms/kg i.m.), and (iv) histological localization in the DRN. Despite behavioral and physiological evidence that all three manipulations induced a stress response, the maximal firing rate of 5-HT neurons was not significantly different from that observed under unstressed conditions. These data are consistent with previous studies from our laboratory which have indicated that very few manipulations are able to perturb the slow and regular activity of these neurons. In contrast, previous work has shown that the firing rate of noradrenergic neurons in the locus ceruleus is dramatically increased by these stressors. The relative imbalance in the activity of these two neuronal groups observed during stress may affect postsynaptic neuronal processing patterns and have adaptive significance during stressful conditions.

Acoustic Stimulation↗
PubMed1988

Inhibitory activity for the interferon-induced protein kinase is associated with the reovirus serotype 1 sigma 3 protein.

In this report we demonstrate that reovirus serotype 1-infected cells contain an inhibitor of the interferon-induced, double-stranded RNA (dsRNA)-dependent protein kinase. We provide evidence that suggests that the virus-encoded sigma 3 protein is likely responsible for this kinase inhibitory activity. We could not detect activation of the dsRNA-dependent protein kinase in extracts prepared from either interferon-treated or untreated reovirus serotype 1-infected mouse L cells under conditions that led to activation of the kinase in extracts prepared from either interferon-treated or untreated, uninfected cells. Extracts from reovirus-infected cells blocked activation of kinase in extracts from interferon-treated cells when the two were mixed prior to assay. The kinase inhibitory activity in extracts of reovirus-infected cells could be overcome by adding approximately 100-fold excess of dsRNA over the amount required to activate kinase in extracts of uninfected cells. Kinase inhibitory activity in extracts of interferon-treated, virus-infected cells could be overcome with somewhat less dsRNA (approximately 10-fold excess). Most of the inhibitory activity in the extracts could be removed by adsorption with immobilized anti-reovirus sigma 3 serum or immobilized dsRNA, suggesting that the dsRNA-binding sigma 3 protein is necessary for kinase inhibitory activity. Purified sigma 3 protein, when added to reaction mixtures containing partially purified kinase, inhibited enzyme activation. Control of activation of this kinase, which can modify eukaryotic protein synthesis initiation factor 2, may be relevant to the sensitivity of reovirus replication to treatment of cells with interferon and to the shutoff of host protein synthesis in reovirus-infected cells.

Animals↗
PubMed1988

Mechanism of interferon action: studies on the activation of protein phosphorylation and the inhibition of translation in cell-free systems.

We describe the ability of reovirus messenger RNA (mRNA) to serve as a template for translation and as an activator of protein phosphorylation in cell-free extracts prepared from untreated and from interferon (IFN)-treated mouse fibroblast L cells. In vitro transcribed reovirus mRNA was purified by column chromatography on CF-11 cellulose. This procedure removed trace amounts of double-stranded RNA (dsRNA) [0.01%-0.1%] present in mRNA preparations purified solely by extensive LiCl precipitation. In the absence of added dsRNA, CF-11 cellulose-purified reovirus mRNA did not detectably activate phosphorylation of either ribosome-associated protein P1 or the alpha subunit of protein synthesis initiation factor eIF-2 in S-10 extracts prepared from L cells; the CF-11 cellulose-purified reovirus mRNA was translated more efficiently than was LiCl-purified reovirus mRNA in these extracts. Highly purified CF-11 reovirus mRNA was, however, translated less efficiently by S-10 extracts prepared from IFN-treated L cells than by extracts prepared from untreated L cells, suggesting that the inefficient translation by IFN-treated extracts was an integral property of reovirus mRNA. Increasing the secondary structure of reovirus mRNA by substituting bromouridine (Br-uridine) for uridine in the mRNA caused an increased inhibition of mRNA binding to ribosomes in extracts prepared from IFN-treated as compared to untreated cells. The mechanism of inhibition of translation of CF-11 cellulose-purified reovirus mRNA in IFN-treated systems remains to be established.

Animals↗
PubMed1988

Histone proteins inhibit activation of the interferon-induced protein kinase by binding to double-stranded RNA.

Bulk calf thymus histone proteins, when included in reaction mixtures, inhibit activation of partially purified double-stranded (ds) RNA-dependent protein kinase, and are themselves only poorly phosphorylated. This inhibition of enzyme activation could be overcome by preincubating enzyme with dsRNA, in the absence of ATP, or by increasing the dsRNA concentration to 100 micrograms/ml. Under these conditions histone proteins were actively phosphorylated. In addition, histone proteins could reverse the nonactivating effects of preincubating enzyme with a high concentration of dsRNA. We demonstrate that histone proteins bind specifically to dsRNA. These results suggest that inhibition of kinase activation by histone is due to competition for binding to available dsRNA. Several virus-encoded inhibitors of the interferon-induced protein kinase are likely dsRNA-binding proteins, which may function in a manner analogous to histone proteins.

Animals↗
PubMed1987

Effects of physiological manipulations on locus coeruleus neuronal activity in freely moving cats. I. Thermoregulatory challenge.

This and the following two papers examine the activity of locus coeruleus noradrenergic (LC-NE) neurons in response to a variety of physiological manipulations in unanesthetized, unrestrained cats. Unit responses were studied during a constant behavioral state in order to avoid the potentially confounding effects of state changes upon LC-NE unit discharge. In the present study, LC-NE unit activity was recorded during two thermoregulatory challenges: ambient heating and pyrogen-induced fever. These two conditions are particularly interesting since the direction of body temperature change that they produce is the same, but the thermoregulatory responses elicited are opposite, i.e. heat loss and heat gain. LC-NE neurons were activated by both manipulations. In response to ambient heating, neuronal activity increased only with the occurrence of panting, and not during earlier portions of the heating session. Following pyrogen administration, LC-NE neurons responded only during the peak increase in body temperature. Both of these effects on unit activity occurred independent of changes in behavioral state. Since both manipulations similarly increased LC-NE unit activity, despite eliciting opposite thermoregulatory responses, it appears that these neurons do not play a specific role in thermoregulation, but may participate in the response to physiological challenges in general.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1987

Effects of physiological manipulations on locus coeruleus neuronal activity in freely moving cats. II. Cardiovascular challenge.

Several cardiovascular manipulations were examined for their effects on single-unit activity of locus coeruleus noradrenergic (LC-NE) neurons in unanesthetized, unrestrained cats: hydralazine (1 mg/kg, i.v.) was administered to present a tonic hypotensive stimulus, and to activate preferentially the neural component of the sympathoadrenal system; hemorrhage was used to decrease blood volume and to activate both the neural and hormonal components of the sympathoadrenal system; intravenous infusion of isotonic saline was used to increase blood volume. LC-NE neurons were activated by hydralazine, in parallel with the sympathetic response (indicated by elevated heart rate and plasma NE). LC-NE unit activity was decreased following a volume load. However, contrary to previous findings in anesthetized animals, hemorrhage had no effect on LC-NE unit activity, but did activate both components of the sympathetic response. It is concluded that: (1) cardiovascular stimuli can influence the activity of LC-NE neurons, though they show less sensitivity to such stimuli than do primary regulatory mechanisms; (2) the response of LC-NE neurons to physiological stimuli can occur independent of changes in behavioral state; (3) these neurons do not appear to play a specific role in cardiovascular regulation, but may respond to physiological challenges in general; (4) finally, in agreement with previous studies, our data show that LC-NE neurons are generally co-activated with the sympathetic nervous system, but also that the two can be dissociated (e.g. hemorrhage).

Action Potentials↗
PubMed1987

Effects of physiological manipulations on locus coeruleus neuronal activity in freely moving cats. III. Glucoregulatory challenge.

Insulin-induced hypoglycemia and the subsequent administration of glucose were examined for their effects on single unit activity of locus coeruleus noradrenergic (LC-NE) neurons in unanesthetized, unrestrained cats. LC-NE neuronal activity showed an inverse relationship to blood glucose levels. The activity of most cells increased during sustained hypoglycemia, and then decreased following glucose administration. Some neurons were unaffected by hypoglycemia, but were inhibited following glucose. The activation of LC-NE neurons in response to insulin administration generally paralleled the increase in plasma epinephrine, although the adrenal response was more sensitive. These data, together with those reported in the preceding papers, suggest the following general conclusions: (1) physiological stimuli can influence the activity of LC-NE neurons in unanesthetized subjects (although they do so less strongly than environmental stimuli); (2) these effects of physiological stimuli upon LC-NE neurons can be exerted independent of changes in behavioral state; (3) LC-NE neurons do not appear to play a specific role in the regulation of any of the systems examined, but may instead play a more global role in the response to physiological challenges in general; (4) LC-NE neurons are generally co-activated with both the neural and hormonal components of the sympatho-adrenal system, although sympathetic activation can occur in the absence of increased LC-NE activity. A previously hypothesized role for LC-NE neurons in facilitating the behavioral response to environmental stressors may thus be extended to include the response to physiological challenges, and perhaps facilitation of the physiological as well as the behavioral components of the stress response.

Action Potentials↗
PubMed1987

Microinjected clonidine inhibits noradrenergic neurons of the locus coeruleus in freely moving cats.

Microinjection of the alpha 2-adrenoceptor agonist, clonidine (CLON; 1.0 microgram/0.1 microliter) effected a virtually complete suppression of the spontaneous activity of noradrenergic neurons of the locus coeruleus in freely moving cats. This effect lasted for approximately 90 min and was reversible by systemic administration of the alpha 2-adrenoceptor antagonist, yohimbine. In contrast, CLON had no consistent effect on the activity of neighboring non-noradrenergic neurons. These results provide additional evidence for the direct inhibition of central noradrenergic neurons by CLON by demonstrating such effects independent of anesthesia or the behavioral effects of systemic drug administration. More generally, these findings demonstrate the usefulness of a technique in which small amounts of drug can be applied in small volumes to produce a neuropharmacologically specific effect upon locally recorded neurons in behaving animals.

Action Potentials↗
PubMed1987

Effect of buspirone on single unit activity in locus coeruleus and dorsal raphe nucleus in behaving cats.

The effects of administration of the non-benzodiazepine anxiolytic buspirone on the spontaneous and sensory evoked single unit activity of serotonergic (5-HT) neurons in the dorsal raphe nucleus and noradrenergic (NE) neurons in the locus coeruleus were examined in freely moving cats. Buspirone (1.0 mg/kg i.p.) strongly suppressed both the spontaneous and evoked activity of 5-HT dorsal raphe nucleus neurons. The spontaneous activity of NE neurons in the locus coeruleus was non-significantly increased by drug administration, while the evoked response was unaffected. These effects occurred during a period of mild behavioral activation. It is suggested that the anxiolytic effects of buspirone administration are not achieved through an action of NE neurons, but may be mediated in part by actions on 5-HT neurons in the dorsal raphe.

Animals↗
PubMed1987

Single-unit responses of serotonergic dorsal raphe nucleus neurons to environmental heating and pyrogen administration in freely moving cats.

Single-unit activity of serotonergic neurons in the dorsal raphe nucleus was examined in response to environmental heating and pyrogen-induced fever in freely moving cats. In the heating study, ambient temperature was rapidly raised from a baseline of 25 degrees to 43 +/- 1 degrees C and maintained at this level for 2 h. Cats displayed hyperthermia, intense panting, and signs of heat stress, however, the discharge rate of serotonergic neurons of the dorsal raphe nucleus was not significantly different from baseline at any time during heat exposure. Similarly, the activity of these neurons was not significantly altered at any time during an approximately 6-h long febrile response induced by the synthetic pyrogen muramyl dipeptide (50 micrograms/kg, i.v.). These results indicate that serotonergic unit activity in the dorsal raphe nucleus is not related to either the activation of behavioral or physiological mechanisms underlying heat defense, or to alterations in thermoregulatory mechanisms during the febrile response to exogenous pyrogen. Furthermore, because these neurons do not respond to an elevation in body temperature induced by either ambient heating or pyrogen, they do not appear to be directly temperature-sensitive. These results do not support a specific role for serotonergic neurons of the dorsal raphe nucleus in thermoregulation.

Animals↗
PubMed1987

Single-unit response of noradrenergic neurons in the locus coeruleus of freely moving cats. I. Acutely presented stressful and nonstressful stimuli.

The present experiment was designed to explore the stress-relatedness of activity in noradrenergic neurons of the locus coeruleus (LC) of behaving cats. A stressor was defined as a stimulus that elicited a significant sympathoadrenal activation as measured by plasma norepinephrine level and heart rate. According to this definition, exposure to 15 min of 100 dB white noise or 15 min of restraint was stressful in cats. In contrast, exposure to inaccessible rats for 15 min was behaviorally activating but nonstressful. The single-unit activity of noradrenergic neurons in the LC of behaving cats was examined under these conditions. The stressful stimuli elicited a significant increase in LC neuronal activity for the entire 15 min stressor duration, whereas the behaviorally activating but nonstressful stimulus elicited no significant change in the activity of these neurons. These results provide evidence that behavioral activation per se is not sufficient to evoke a tonic activation of these neurons. Rather, these data support the hypothesis that the LC is involved in the CNS response to stress and provide additional evidence that the activity of LC noradrenergic neurons increases in association with sympathoadrenal activation.

Animals↗
PubMed1987

Single-unit response of noradrenergic neurons in the locus coeruleus of freely moving cats. II. Adaptation to chronically presented stressful stimuli.

The preceding paper described a stress-related tonic activation of noradrenergic neurons of the locus coeruleus (LC) of behaving cats. The present study examined the degree to which adaptation to stress was reflected in LC unit activity. Adaptation was defined as a reduction in the magnitude of the physiological stress response of the animal, as reflected in plasma norepinephrine level and heart rate. Adaptation of the physiological stress response occurred after 5 repeated hourly presentations of 100 dB white noise and after 2 hr of restraint. When these stimuli ceased to elicit significant sympathoadrenal activation, they likewise ceased to elicit activation of LC single-unit activity. These results provide further support for the hypothesis that tonic elevations in LC neuronal activity are stress related and that the LC is involved in the CNS response to challenges to the organism.

Adaptation, Physiological↗