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Biomedical subjects

F R Morales

Publications and source records attributed to F R Morales.

At least 55 records · Page 3Linked to original sources
PubMed1995

Effects of excitatory amino acid antagonists on the phasic depolarizing events that occur in lumbar motoneurons during REM periods of active sleep.

The membrane potential of lumbar motoneurons is dominated during the tonic periods of active sleep by glycine-mediated inhibitory postsynaptic potentials (IPSPs). During the phasic rapid eye movement (REM) periods of active sleep there are also IPSPs but, in addition, the membrane potential exhibits depolarizing shifts and action potentials that occur in conjunction with the phasic activation of the somatic musculature. The present study was designed to provide evidence that an excitatory amino acid (EAA) neurotransmitter is responsible for these patterns of motoneuronal activation. It was found that juxtacellular microiontophoretic applications of kynurenic acid a non-NMDA antagonist of EAA neurotransmission, blocked the depolarizing potentials of motoneurons that arise during the REM periods of active sleep. In contrast, the selective NMDA receptor antagonist APV did not block these depolarizations. The conclusion is drawn that the myoclonic twitches and jerks that characterize that REM periods of active sleep are dependent upon the excitation of motoneurons that occurs as a result of EAAs acting at non-NMDA receptors.

2-Amino-5-phosphonovalerate↗
PubMed1994

The control of jaw-opener motoneurons during active sleep.

Brainstem and spinal cord motoneurons that innervate somatic musculature serving antigravity functions are postsynaptically inhibited during active sleep. However, it has been reported that hypoglossal motoneurons (which do not innervate antigravity muscles) are not postsynaptically inhibited during active sleep, but are disfacilitated. In the present report we describe changes, during active sleep, in the excitability and membrane potential of digastric and synergistic motoneurons of the trigeminal motor pool; these neurons do not perform antigravity functions. The experiments described in the present report were performed in chronic cats that were prepared for intracellular recording. The motoneurons hyperpolarized an average of 11 mV (S.D. +/- 1.29, n = 8, P < 0.005) during active sleep compared to quiet sleep. Hyperpolarization was accompanied by a reduction in the excitability of the somadendritic regions of the neurons, as indicated by an increase in the delay of propagation of antidromic spikes from the initial segment to the somadendritic portion of the cell. High gain membrane potential recordings from these motoneurons revealed the occurrence of a remarkably large number of hyperpolarizing potentials during active sleep. When K-chloride-filled microelectrodes were utilized and chloride ions were injected intracellularly, the polarity of these potentials was reversed. During phasic episodes of active sleep, there was a clear increase in hyperpolarizing potential activity, a blockade of somadendritic spikes and phasic reductions in the amplitude of the initial segment spikes. Hyperpolarizing potentials occurred in conjunction with ponto-geniculo-occipital waves.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1994

State dependency of the effects of microinjection of cholinergic drugs into the nucleus pontis oralis.

The microinjection of cholinergic drugs into the pontine reticular formation elicits active sleep-like states that are comprised of the principal physiological patterns of activity that characterize naturally-occurring active sleep, i.e., EEG desynchronization, PGO waves, rapid eye movements and atonia. We have reported that other behavioral states arise even when cholinergic drugs are injected into the exact same reticular location. The present study was conducted to explore the basis for the differences in the drug effect. A combination of acetylcholine and neostigmine was injected by microiontophoresis into the dorsal region of the nucleus pontis oralis in four chronic, unanesthetized cats. The states that were induced by cholinergic drug injection depended on the state of the animal at the time of the injection. When the animal was awake, cholinergic injections resulted in a waking-dissociated state, which was characterized by EEG desynchronization and muscle atonia in a cat that appeared to be awake and was able to track objects in its visual field. If the cat was in quiet sleep at the time of the injection, an active sleep-like state followed that was indistinguishable from naturally-occurring active sleep; on a few occasions following cholinergic injections during quiet sleep there was a quiet sleep-dissociated state, which was characterized by PGO waves and muscle atonia in the cat that by other indices appeared to be in quiet sleep. The results of this study indicate that the state of the animal at the time of drug injection is a critical variable that influences the responses which are induced by cholinergic stimulation of the pontine reticular formation.

Animals↗
PubMed1993

C-fos expression in the pons and medulla of the cat during carbachol-induced active sleep.

Microinjection of carbachol into the rostral pontine tegmentum of the cat induces a state that is comparable to naturally occurring active (REM, rapid eye movement) sleep. We sought to determine, during this pharmacologically induced behavioral state, which we refer to as active sleep-carbachol, the distribution of activated neuron within the pons and medulla using c-fos immunocytochemistry as a functional marker. Compared with control cats, which were injected with saline, active sleep-carbachol cats exhibited higher numbers of c-fos-expressing neurons in (1) the medial and portions of the lateral reticular formation of the pons and medulla, (2) nuclei in the dorsolateral rostral pons, (3) various raphe nuclei, including the dorsal, central superior, magnus, pallidus, and obscurus, (4) the medial and lateral vestibular, prepositus hypoglossi, and intercalatus nuclei, and (5) the abducens nuclei. On the other hand, the mean number of c-fos-expressing neurons found in the masseter, facial, and hypoglossal nuclei was lower in carbachol-injected than in control cats. The data indicate that c-fos expression can be employed as a marker of state-dependent neuronal activity. The specific sites in which there were greater numbers of c-fos-expressing neurons during active sleep-carbachol are discussed in relation to the state of active sleep, as well as the functional role that these sites play in generating the various physiological patterns of activity that occur during this state.

Animals↗
PubMed1992

Passive electrical properties of motoneurons in aged cats following axotomy.

The objective of this study was to determine whether the aging process influences the changes in the electrophysiological properties of motoneurons that occur as a consequence of axotomy. Accordingly, using intracellular recording and stimulating techniques, the basic electrical properties of control (unaxotomized) and axotomized spinal cord motoneurons of aged cats were determined. Compared with control motoneurons, axotomized motoneurons exhibited increases in input resistance (Rin), membrane time constant (tau b) and the equalizing time constant (tau c). While the electrotonic length (L) remained unchanged, axotomy induced a decrease in the total cell capacitance (Ccell). The post-axotomy reduction of Ccell indicates that the motoneuron surface area was reduced and the increased membrane time constant indicates that there was an increase in membrane resistivity (Rm). The post-axotomy conservation of L accompanied by an increase in Rm suggests that aged axotomized motoneurons undergo geometrical changes. Furthermore, calculations based on cable theory suggest that the diameter of the equivalent cylinder (d) decreased following axotomy, whereas the equivalent cylinder length (l) remained unaffected. It is concluded that axotomy produces significant alterations in the soma-dendritic portion of aged spinal motoneurons, as indicated by the changes found in their passive electrophysiological properties, and that the pattern of the response that occurs in axotomized motoneurons of adult cats is also present in axotomized motoneurons of aged animals.

Aging↗
PubMed1992

PGO-related potentials in lumbar motoneurons during active sleep.

1. The present report describes the relationship that occurs during active sleep between ponto-geniculo-occipital (PGO) waves and changes in spinal cord motoneuron membrane potential. 2. These changes were characterized by the appearance of a complex pattern of motoneuron hyperpolarizing potentials, with a duration of approximately 300 ms, that were centered around the PGO wave. The first hyperpolarizing potential began before the onset of the PGO wave. Emerging from this hyperpolarizing potential was a second, larger-amplitude hyperpolarizing potential; it was followed by a succession of smaller-amplitude hyperpolarizations. 3. All potentials were present in conjunction with PGO waves during active sleep, but they were observed only in some motoneurons when PGO waves occurred during the transition period from quiet sleep to active sleep. 4. The potentials were reversed by chloride, demonstrating that they were inhibitory postsynaptic potentials (IPSPs). 5. These data, combined with the fact that these PGO-related IPSPs are blocked by strychnine, support the hypothesis that they are the result of the phasic enhancement of the activity of the same system that inhibits motoneurons during active sleep.

Action Potentials↗
PubMed1991

Strychnine blockade of the non-reciprocal inhibition of trigeminal motoneurons induced by stimulation of the parvocellular reticular formation.

Stimulation of a region within the parvocellular medullary reticular formation (PcRF) that contains somas of premotor interneurons produces short latency inhibitory synaptic potentials (IPSPs) in cat trigeminal motoneurons. The present study was undertaken to determine whether glycinergic synapses are responsible for these IPSPs. The intravenous administration of strychnine, an established glycine antagonist, abolished these PcRF-IPSPs. This effect appears to be specific for glycinergic inhibitory synapses because the short lasting component of the IPSP produced by inferior alveolar nerve (IAN) stimulation was also abolished, whereas, in contrast, the long lasting non-glycinergic component of this IPSP was not suppressed. These results indicate that a glycinergic system in the reticular formation is responsible for the non-reciprocal postsynaptic inhibition of trigeminal motoneurons.

Animals↗
PubMed1991

Electrophysiological characteristics of the Mauthner cell of the weakly electric fish Gymnotus carapo.

The Mauthner cell (M-cell) of the 'weakly electric fish' Gymnotus carapo was investigated with electrophysiological techniques. The antidromic action potential, the recurrent inhibitory input and the posterior VIIIth nerve excitatory input in this cell exhibited characteristics similar to those described in the goldfish. In addition, we found an excitatory input evoked by spinal stimulation at intensities subthreshold for M-cell axons.

Animals↗
PubMed1991

Expression of insulin-like growth factor I, its binding proteins, and its receptor in ovarian cancer.

Insulin-like growth factor (IGF) I is a polypeptide hormone important in normal growth and development. Although IGF-I is a mitogen for many cancer cell lines, previous work has suggested that autocrine production of IGF-I is uncommon in cancers of epithelial origin. In this study, expression of IGF-I, its binding proteins, and its receptor were examined in ovarian cancer cell lines and tissues. Of 10 ovarian cancer cell lines, 3 (OVCAR-3, OVCAR-7, and PEO4) expressed IGF-I mRNA. RNase protection assays using probes derived from IGF-IA, IGF-IB, and alternate exon 1 IGF-I complementary DNAs demonstrated that these cells contained a predominant IGF-I transcript with an alternate first exon. RNA extracted from primary and metastatic ovarian cancer tissues also expressed IGF-I mRNAs (7 of 7) with the alternate first exon. IGF-I protein was detected in OVCAR-3-conditioned media; this activity was secreted in conjunction with several IGF-binding proteins (IGFBPs). IGFBP-2, IGFBP-3, an Mr 24,000 species, and an Mr 30,000 species could also be demonstrated in OVCAR-3. Type I IGF receptor mRNA was found in all 10 of the ovarian cancer cell lines and all 7 of the primary or metastatic ovarian cancer tissues. IGF-I was a mitogen for OVCAR-3, demonstrating the presence of a functional type I IGF receptor. These data show that all the necessary components for an IGF-I-mediated autocrine loop are expressed by ovarian cancer cells.

Blotting, Northern↗
PubMed1991

A medullary inhibitory region for trigeminal motoneurons in the cat.

The present report describes the effects on trigeminal motoneurons of stimulation of a circumscribed site within the parvocellular region of the medullary reticular formation. This medullary site was selected because anatomical studies have shown that premotor interneurons project from this site to the trigeminal motorpool. Electrical stimulation of this site induced IPSPs (PcRF-IPSPs) in jaw-closer motoneurons. A population of these IPSPs, recorded contralateral to the site of stimulation, exhibited latencies shorter than 1.5 ms (mean 1.16 +/- 0.08 SD). Their mean amplitude was 1.72 mV +/- 1.13 SD and their mean duration was 3.52 ms +/- 2.15 SD. We believe that these PcRF-IPSPs arose as the result of activation of a monosynaptic pathway. A comparable inhibitory input from this site to ipsilateral jaw-closer motoneurons and to both contra and ipsilateral digastric motoneurons was also observed. We therefore conclude that this medullary PcRF site contains premotor interneurons that are capable of postsynaptically inhibiting motoneurons that innervate antagonistic jaw muscles.

Animals↗
PubMed1991

The postsynaptic inhibitory control of lumbar motoneurons during the atonia of active sleep: effect of strychnine on motoneuron properties.

The present study examined the effects of strychnine on the tonic hyperpolarization and the changes in membrane properties of lumbar motoneurons that occur during active sleep. To carry out these studies, intracellular recordings from lumbar motoneurons were combined with the juxtacellular microiontophoretic application of strychnine in chronic, undrugged, normally respiring cats. During active sleep, compared to quiet sleep, motoneurons that were not exposed to strychnine exhibited tonic hyperpolarization, a decrease in cell excitability, and an increase in membrane conductance; they were also bombarded by high-frequency, large-amplitude IPSPs. In conjunction with the juxtacellular application of strychnine, there was a marked reduction in the degree of hyperpolarization during active sleep; motoneuron excitability was no longer suppressed, and there was a reduction in the increase in membrane conductance. In addition, the large-amplitude IPSPs were blocked. These results identify glycine as the neurotransmitter responsible for the state-dependent changes in membrane properties and the hyperpolarization of motoneurons that takes place during active sleep.

Action Potentials↗
PubMed1990

Suppression of the PGO-related lumbar motoneuron IPSP by strychnine.

Intracellular recordings from lumbar motoneurons in chronic unanesthetized cats revealed that a distinct inhibitory postsynaptic potential (IPSP) occurs following pontogeniculooccipital (PGO) waves during active sleep. Strychnine, when applied juxtacellularly by microiontophoresis, was found to block this IPSP. These data suggest that glycine is likely to be the neurotransmitter that is responsible for the inhibition of lumbar motoneurons that occurs in conjunction with the PGO waves of active sleep.

Action Potentials↗
PubMed1990

Non-reciprocal postsynaptic inhibition of digastric motoneurons.

This study was undertaken to explore the effects, on digastric motoneurons, of electrical stimulation of a site within the parvocellular medullary reticular formation (PcRF). This site is located lateral to the hypoglossal nucleus and ventral to the dorsal motor nucleus of the vagus nerve. Within this site are somas of premotor interneurons that project to trigeminal motor nuclei. Stimulation of this site resulted in the generation of IPSPs in digastric motoneurons. We postulate that these IPSPs were due to the activation of a monosynaptic path from the PcRF to digastric motoneurons. The present results, in conjunction with those previously reported which indicate that the PcRF also induces monosynaptic IPSPs in masseter motoneurons, demonstrate that this is a site of origin for the postsynaptic inhibitory control of motoneurons that innervate both jaw opening and closing muscles.

Animals↗
PubMed1990

Medullary control of lumbar motoneurons during carbachol-induced motor inhibition.

The present study examined the effects of stimulation of the medullary nucleus reticularis gigantocellularis (NRGc) on the Ia-monosynaptic reflex and the membrane potential of lumbar motoneurons. Stimulation of the NRGc was carried out in acute decerebrate cats during motor suppression induced by the intrapontine microinjection of carbachol. During carbachol-induced motor suppression, compared with control conditions (prior to the administration of carbachol), NRGc stimulation resulted in a statistically significant reduction in the Ia-monosynaptic reflex. This effect was maximal at an interval of 45 ms following NRGc stimulation. NRGc stimulation also induced, in lumbar motoneurons, a large amplitude (3.17 mV +/- 0.36 [S.E.M.]), long duration (54.73 ms +/- 3.52 [S.E.M.]) inhibitory postsynaptic potential whose peak coincided with the interval of maximum reflex suppression. These results suggest that carbachol activates pontine neurons that excite cells of the medullary NRGc. We believe that these medullary neurons, in addition to those of the nucleus pontis oralis (NPO)7, participate in the modulation of the descending inhibitory pathway that is responsible for the phenomenon of response-reversal and generalized atonia during naturally occurring active (i.e. REM) sleep.

Animals↗
PubMed1990

The atonia and myoclonia of active (REM) sleep.

Postsynaptic inhibition is a principal process responsible not only for the atonia of the somatic musculature during active sleep but also for the phasic episodes of decreased motoneuron excitability that accompany bursts of REMs during this state. These postsynaptic processes are dependent upon the presence of active sleep-specific IPSPs, which are apparently mediated by glycine. The phasic excitation of motoneurons during REM periods is due to excitatory postsynaptic potentials that, when present, encounter a motoneuron already subjected to enhanced postsynaptic inhibition. These EPSPs are mediated by a non-NMDA neurotransmitter. Thus, from the perspective of motoneurons, active sleep can be characterized as a state abundant in the availability of strikingly potent patterns of postsynaptic inhibition and, during REM periods, not only by enhanced postsynaptic excitation, but also by enhanced postsynaptic inhibition. The site of origin of these inhibitory and excitatory drives is, at present, less clearly defined. There is a consensus that the structure(s) from which the inhibitory drives emanate are located in the lower brainstem, with a cholinoceptive trigger zone situated in the dorsolateral pontine tegmentum in or in the vicinity of the nucleus pontis oralis. We have suggested that from this cholinoceptive trigger zone there emanates an excitatory drive that directly, or through interneurons, excites a medullary are in or in the vicinity of the nucleus reticularis gigantocellularis. Thus, a cascade of cholinoceptively activated excitatory activity proceeds to eventually activate inhibitory interneurons whose activation results in motoneuron inhibition and muscle atonia during active sleep. Resolution of the precise location and mechanisms of interaction of the supraspinal inhibitory and excitatory motoneuron control mechanism constitutes a major goal of future experiments and the next major challenge for researchers in this field.

Brain Stem↗
PubMed1989

Cable properties of spinal cord motoneurons in adult and aged cats.

1. The electrophysiological properties of spinal cord alpha-motoneurons were investigated in adult cats (1-3 yr old) and old cats (14-15 yr old) using intracellular recording techniques. Voltage transients following depolarizing pulses of current were analyzed according to the procedure described by Ito and Oshima (15). The input resistance of each cell, together with the passive electrical time constants, were used to estimate the electrotonic length and total cell capacitance of each motoneuron. 2. Adult and old motoneurons both exhibited an undershoot of the membrane potential following the cessation of a subthreshold depolarizing current pulse (15). The average time constant for the decay of this undershoot in membrane potential was statistically indistinguishable in motoneurons of adult and aged animals. 3. The average membrane time constant of motoneurons in aged cats was 19% longer than that of motoneurons in adult cats. 4. The average total cell capacitance of motoneurons in aged cats was 16% smaller than that of motoneurons in adult cats. 5. The average electrotonic length of old motoneurons was statistically indistinguishable from that of motoneurons in adult cats. 6. From these results, we conclude that there is an age-dependent increase in the membrane resistance and an age-dependent decrease in cell surface area of alpha-motoneurons of the lumbar spinal cord in aged cats. Both of these phenomena are believed to contribute to the age-dependent increase in input resistance that has been previously reported to occur in motoneurons in aged cats (18).

Aging↗
PubMed1989

Evidence that glycine mediates the postsynaptic potentials that inhibit lumbar motoneurons during the atonia of active sleep.

Postsynaptic inhibition of somatic motoneurons underlies the atonia of active sleep. This inhibitory control depends, in large measure, on the bombardment of motoneurons during active sleep by a unique class of large-amplitude inhibitory postsynaptic potentials (IPSPs). These potentials are present only during this behavioral state and have therefore been designated as active sleep-specific IPSPs (AS-IPSPs). The present study was concerned with determining the neurotransmitter that mediates these AS-IPSPs. Lumbar motoneurons were recorded intracellularly during quiet and active sleep in intact, undrugged, normally respiring cats. The frequency and waveform parameters of the inhibitory postsynaptic potentials recorded from these motoneurons were examined following the microiontophoretic juxta-cellular administration of strychnine (a glycine receptor antagonist) and picrotoxin and bicuculline (GABA receptor antagonists). Microiontophoretically applied strychnine abolished the AS-IPSPs and a majority of smaller-amplitude IPSPs. Neither picrotoxin nor bicuculline modified the frequency, amplitude, or rising phase of the AS-IPSPs or the smaller-amplitude IPSPs. We conclude that the postsynaptic inhibitory drive that impinges on motoneurons during active sleep is principally mediated by glycine or a glycinergic substance.

Animals↗