Biomedical subjects

M H Chase

Publications and source records attributed to M H Chase.

At least 55 records · Page 3Linked to original sources

PubMed1996

Cell size and geometry of spinal cord motoneurons in the adult cat following the intramuscular injection of adriamycin: comparison with data from aged cats.

Adriamycin (ADM), an antineoplastic antibiotic, when injected intramuscularly, is taken up by motoneuron axonal terminals and retrogradely transported to the motoneuron soma where it exerts its neurotoxic effect. In the present study, ADM was injected into the hindlimb muscles of five adult cats. Measurements of the electrophysiological properties of the lumbar motoneurons innervating these muscles were obtained using intracellular techniques. Based upon these data the equivalent cylinder model of motoneurons was employed to evaluate ADM-induced changes in cell size and cell geometry. The size of cell somas in the ventral horn was also measured using light microscopy and computer imaging software. There were significant increases in the membrane time constant (25%) and input resistance (50%) in motoneurons whose muscles were treated with ADM (ADM-MNs) compared with data from control motoneurons (control-MNs). The increase in membrane time constant is attributed to an increase in membrane resistance; the increase in input resistance appears to depend upon both an increase in membrane resistance and a decrease in total cell surface area. Cell capacitance, which is proportional to the total cell surface area, was significantly reduced (15%) in ADM-MNs. Calculations based on cable theory indicate that while there was no significant change in the length of the equivalent cylinder for ADM-MNs, there was a significant decrease (17%) in the diameter of the equivalent cylinder. These data indicate that there is a decrease in total cell surface area which can be attributed to the shrinkage of branches throughout the dendritic tree. There was also a small (7%) but statistically significant decrease in the electrotonic length of ADM-MNs. Morphological analysis also revealed that the mean cross-sectional area of the somas of those ventral horn neurons which are likely to correspond to the motoneuron population was significantly reduced on the ADM-treated side compared to that of neurons on the control side. We conclude that significant geometrical changes were induced in lumbar motoneurons of adult cats after ADM was injected to their muscles. In old cats, spinal cord motoneurons exhibit similar patterns of changes in their electrophysiological characteristics which have also been suggested to be correlated with changes in cell geometry. The question then arises as to whether the response of motoneurons to ADM and the aging process reflects a stereotypic reaction of motoneurons to a variety of insults or whether the response to ADM mirrors specific aspects of the aging process.

Aging↗

PubMed1996

Age-related changes in soma size of neurons in the spinal cord motor column of the cat.

The present study was undertaken to examine the effect of the aging process on the soma size and number of motoneurons and interneurons in the motor column of the spinal cord of old cats. Neurons in the motor column were divided into small and large populations based on a bimodal distribution of their soma cross-sectional areas. A 17% decrease in the cross-sectional area of small neurons was observed, this decrease was statistically significant (P < 0.0001). The cross-sectional area of large neurons decreased by only 6%, which was statistically significant (P < 0.05). On the other hand, there was no significant difference in the number of large, small or of these combined population of ventral horn neurons in the aged cats compared with the control animals. This data suggest that neurons in the motor column are not uniformly affected by the aging process because morphological changes are proportionally greater in small neurons than in large neurons.

Aging↗

PubMed1996

State-dependent phenomena in cat masseter motoneurons.

In the present study we explored the mechanisms of carbachol-induced muscle atonia in the alpha-chloralose-anesthetized animal. We compared our findings to those that have been previously obtained in unanesthetized cats during muscle atonia occurring during natural active sleep. Accordingly, in cats anesthetized with alpha-chloralose, intracellular records were obtained from masseter motoneurons before and after carbachol-induced motor atonia. Following the induction of atonia, the membrane potential activity was dominated by high-frequency, discrete, hyperpolarizing potentials. These hyperpolarizing potentials were reversed in polarity by the intracellular injection of chloride ions and abolished by the application of strychnine. These findings indicate that they were inhibitory postsynaptic potentials (IPSPs) mediated by glycine. These IPSPs appeared exclusively during muscle atonia. In addition, masseter motoneurons were significantly hyperpolarized and their rheobase increased. There was a decrease in input resistance and membrane time constant. In the alpha-chloralose-anesthetized preparation, stimulation of the nucleus pontis oralis (NPO) induced IPSPs in masseter motoneurons following, but never prior to, the pontine injection of carbachol. Thus, this is the first demonstration that "reticular response-reversal' may be elicited in an anesthetized preparation. Another state-dependent phenomenon of active sleep, the occurrence of IPSPs in motoneurons that are temporally correlated with ponto-geniculo-occipital (PGO) waves, was also observed in this preparation only after carbachol administration. Based on the data in this report, we conclude that the inhibitory system that mediates atonia during the state of active sleep can be activated in an animal that is anesthetized with alpha-chloralose. Specifically, the neuronal groups that generate spontaneous IPSPs, those that mediate the phenomenon of reticular response-reversal, and those involved in the generation of PGO waves are capable of being activated and remain functional during alpha-chloralose-anesthesia.

Anesthesia↗

PubMed1995

Muscle atonia can be induced by carbachol injections into the nucleus pontis oralis in cats anesthetized with alpha-chloralose.

Cholinergic excitation of structures in the pontine reticular formation appears to be a key step in the generation of active sleep. For example, muscle atonia which occurs as a result of the postsynaptic inhibition of motoneurons during active sleep is also present after carbachol, a cholinergic agonist, is injected into the nucleus pontis oralis. In the present study, in order to obtain information regarding the mechanisms that generate atonia during active sleep and to provide a paradigm for studying atonia in anesthetized cats, we determined whether cholinergically induced atonia could be generated in an animal that was anesthetized with alpha-chloralose. Cats which were initially anesthetized with alpha-chloralose (40 mg/kg, I.V.) exhibited spikes in the EEG, hippocampus and lateral geniculate nuclei. Muscle atonia occurred after carbachol (200 mM) was injected by microiontophoresis (300-500 nA) into the nucleus pontis oralis; the spikes in the EEG, hippocampus and lateral geniculate nuclei were still present. We believe that the atonia induced by carbachol in alpha-chloralose-anesthetized cats is mediated by the same mechanisms that operate during active sleep in the unanesthetized animal for the following reasons. First, in the same cats when they were not anesthetized with alpha-chloralose, carbachol injections in the identical brainstem sites induced active sleep with its accompanying pattern of muscle atonia. Second, after carbachol was injected into the same sites in alpha-chloralose-anesthetized cats, intracellular recordings from lumbar motoneurons revealed that inhibitory postsynaptic potentials were bombarding motoneurons; these inhibitory potentials were similar to those which are present during naturally occurring active sleep. In addition, stimulation of the nucleus reticularis gigantocellularis (NRGc) was found to induce large amplitude depolarizing potentials in lumbar motoneurons in alpha-chloralose-anesthetized cats prior to the administration of carbachol, whereas after its administration, accompanying muscle atonia there were large amplitude hyperpolarizing potentials and a reduction in the amplitude of depolarizing potentials. We therefore conclude that the cholinergically induced processes that initiate and maintain muscle atonia are not blocked by the actions of alpha-chloralose.

Animals↗

PubMed1995

Experimental analysis of the method of 'peeling' exponentials for measuring passive electrical properties of mammalian motoneurons.

Trigeminal motoneurons of the guinea pig brain stem slice preparation were studied using intracellular recording techniques. The voltage response to a 100-ms constant-current pulse was studied and a population of cells was found which did not exhibit sag or overshoot of their voltage response to a pulse of hyperpolarizing current of < 1 nA but did exhibit both phenomena when a current pulse of > 1 nA was used. The sag and overshoot observed with large-current pulses were reduced or blocked when 4 mM CsCl was added to the bathing solution. This observation supports the hypothesis that these phenomena were due to the voltage- and time-dependent activation of the Q-current. The method of peeling exponentials was then used to correct raw voltage data from cells in which the Q-current was present. The mean membrane time constant was within 1% and the mean input resistance was within 2% of the means for these parameters when measured in these same cells under conditions in which the Q-current was absent. We conclude from these experiments that the method of peeling exponentials is valid for obtaining estimates of the membrane time constant and input resistance from cells that exhibit sag and overshoot due to voltage- and time-dependent changes in the magnitude of the Q-current.

Action Potentials↗

PubMed1995

Fos and serotonin immunoreactivity in the raphe nuclei of the cat during carbachol-induced active sleep: a double-labeling study.

The microinjection of carbachol into the nucleus pontis oralis produces a state which is polygraphically and behaviorally similar to active sleep (rapid eye movement sleep). In the present study, using double-labeling techniques for serotonin and the protein product of c-fos (Fos), we sought to examine whether immunocytochemically identified serotonergic neurons of the raphe nuclei of the cat were activated, as indicated by their expression of c-fos, during this pharmacologically-induced behavioral state (active sleep-carbachol). Compared with control cats, which were injected with saline, active sleep-carbachol cats exhibited a significantly greater number of c-fos-expressing neurons in the raphe dorsalis, magnus and pallidus. Whereas most of the c-fos-expressing neurons in the raphe dorsalis were small, those in the raphe magnus were medium-sized and in the raphe pallidus they were small and medium-sized. The mean number of serotonergic neurons that expressed c-fos (i.e. double-labeled cells) was similar in control and active sleep-carbachol cats. These data indicate that there is an increased number of non-serotonergic, c-fos-expressing neurons in the raphe dorsalis, magnus and pallidus during the carbachol-induced state.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Induction of rapid eye movement sleep by the microinjection of nerve growth factor into the pontine reticular formation of the cat.

Nerve growth factor is an endogenous protein which belongs to the neurotrophin family of trophic factors. According to the neurotrophic hypothesis, neurotrophins are synthetized by target tissues and regulate the survival and phenotype of their innervating neurons. Whereas these trophic molecules have been mainly thought to be involved in developmental processes, their existence in the central nervous system of the adult animal suggests that they may play a role in neuronal physiology. Recently, it has been reported that neurons that express messenger RNA for two neurotrophins, namely brain-derived neurotrophic factor and neurotrophin-3, are located medial to the locus coeruleus and ventral to the fourth ventricle. This area corresponds to the latero-dorsal tegmental nucleus, which contains cholinergic neurons that have been implicated in the generation of rapid eye movement sleep. In turn, the laterodorsal tegmental nucleus is reciprocally connected with the nucleus pontis oralis in the rostrodorsal pontine reticular formation, which is an area that is involved in the initiation of the physiological patterns of activity that define the state of rapid eye movement sleep. Scattered neurons in the nucleus pontis oralis express the low-affinity nerve growth factor receptor which also binds the other neurotrophins with similar affinity. In addition, neurons in the area of the nucleus pontis oralis have been reported to express a subtype of the neurotrophin high affinity receptors. These membrane receptors, independently or in combination with the low affinity receptors, have been proposed to mediate the delayed, long-term effects of neurotrophins.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Changes in the electrophysiological properties of cat spinal motoneurons following the intramuscular injection of adriamycin compared with changes in the properties of motoneurons in aged cats.

1. This study was undertaken to investigate the effects of adriamycin (ADM, Doxorubicin) on the basic electrophysiological properties of spinal cord motoneurons in the adult cat. ADM was injected into the biceps, gastrocnemius, semitendinosus, and semimembranosus muscles of the left hindlimb (1.2 mg per muscle). Intracellular recordings from motoneurons innervating these muscles were carried out 12, 20, or 40 days after ADM administration and from corresponding motoneurons in untreated control cats. 2. Twelve days after ADM injection, motoneurons innervating ADM-treated muscles (ADM MNs) exhibited statistically significant increases in input resistance, membrane time constant, and amplitude of the action potential's afterhyperpolarization (AHP). In addition, there was a statistically significant decrease in rheobase and in the delay between the action potential of the initial segment (IS) and that of the somadendritic (SD) portion of the motoneuron (IS-SD delay). There were no significant changes in the resting membrane potential, threshold depolarization, action potential amplitude, or axonal conduction velocity. 3. The changes in electrical properties of motoneurons at 20 and 40 days after ADM injection were qualitatively similar to those observed at 12 days. However, at 40 days after ADM injection there was a statistically significant decrease in the axonal conduction velocity of the ADM MNs. 4. The normal correlations that are present between the AHP duration and electrical properties of the control motoneurons were observed in the ADM MNs, e.g., AHP duration was positively correlated with the input resistance and time constant and negatively correlated with the axonal conduction velocity. The correlation coefficients, however, were reduced in comparison with the control data. 5. This study demonstrates that ADM exerts significant effects on the electrical properties of motoneurons when injected into their target muscles. The majority of the changes in motoneuron electrical properties caused by ADM resemble those observed in motoneurons of aged cats. Additional research is required to determine whether the specific changes induced in motoneurons by ADM and those that occur in motoneurons in old age are due to similar degradative mechanisms.

Action Potentials↗

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↗

PubMed1994

Conditioning of brain stimulation-induced presleep behavior.

Experiments were conducted on three chronic unanesthetized, undrugged cats. Electrical stimulation of the basal forebrain area (BFA) resulted in presleep behavior (i.e., the cats would sit or lie down, and EEG spindles would arise). After several sessions (conducted twice a week), two of these cats began to exhibit presleep behavior almost immediately after entering the experimental compartment, even before the application of BFA stimulation. The third cat often ate some food (which was always present in the compartment) before showing presleep behavior. When stimulation was withheld during an extinction procedure, the cats still exhibited presleep behavior in the absence of stimulation during several sessions. We conclude that repeated BFA stimulation led to conditioning of the stimulation effects, that is, the presleep behavior that was evoked by the environmental situation alone, without BFA stimulation or any other intermittent stimulus.

Action Potentials↗

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

Age-dependent changes in cat masseter nerve: an electrophysiological and morphological study.

The present study was undertaken to determine the manner in which aging affects the function and structure of the masseter nerve in old cats. Electrophysiological data demonstrated a significant decrease in the conduction velocity of the action potential in old cats compared with that observed in adult cats. Light microscopic analyses revealed an age-dependent decrease in axon diameter. Electron microscopic observations of the masseter nerve in the aged cats revealed a disruption of the myelin sheaths and a pronounced increase in collagen fibers in the endoneurium and perineurium. These morphological changes are discussed and then related to the decrease in conduction velocity which was observed in the electrophysiological portion of this study.

Aging↗

PubMed1992

Passive electrophysiological properties of aged and axotomized cat spinal cord motoneurons: the effect of cell size and electrode shunt.

Intracellular recordings were obtained from intact and axotomized lumbar motoneurons of aged cats. The sub-threshold electrical properties of these cells were measured, including input resistance, resting membrane potential, and the first two equalizing time constants as well as their associated amplitude constants. These data were used in a semi-infinite cable model of the motoneuron to estimate the size of the shunt resistance (Rshunt) which is created when the electrode penetrates the cell membrane. The average Rshunt for intact aged cells was 5.35 +/- 1.01 M omega, while that for the axotomized aged cells was 8.93 +/- 1.20 M omega. The statistically significant difference in mean shunt magnitude did not affect the measurements of membrane time constant because this constant is independent of the shunt in this model of the motoneuron. However, the determination of cell input resistance, which is not independent of the shunt, was shown to underestimate the real cell input resistance by 23-29%. We therefore conclude that the shunt resistance is an important factor which should be taken into account when measuring input resistance.

Aging↗

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↗