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S J Fung

Publications and source records attributed to S J Fung.

At least 37 records · Page 2Linked to original sources

Locus coeruleus control of spinal motor output.

Using electrophysiological techniques, we investigated the functional properties of the coeruleospinal system for regulating the somatomotor outflow at lumbar cord levels. Many of the fast-conducting, antidromically activated coeruleospinal units were shown to exhibit the alpha 2-receptor response common to noradrenergic locus coeruleus (LC) neurons. Electrically activating the coeruleospinal system potentiated the lumbar monosynaptic reflex and depolarized hindlimb flexor and extensor motoneurons via an alpha 1-receptor mechanism. The latter synaptically induced membrane depolarization was mimicked by norepinephrine applied iontophoretically to motoneurons. That LC inhibited Renshaw cell activity and induced a positive dorsal root potential at the lumbar cord also reinforced LC's action on motor excitation. We conclude that LC augments the somatomotor output, at least in part, via an alpha 1-adrenoceptor-mediated excitation of ventral horn motoneurons. Such process is being strengthened by LC's suppression of the recurrent inhibition pathway as well as by its presynaptic facilitation of afferent impulse transmission at the spinal cord level.

Action Potentials↗

Localization of enkephalinergic neurons in the dorsolateral pontine tegmentum projecting to the spinal cord of the cat.

The dorsolateral pontine tegmentum of the cat is known to contain enkephalinergic neurons, with most of the enkephalin co-contained in the catecholaminergic neurons; however, enkephalinergic cells projecting to the spinal cord have not been identified. This study employs retrograde transport of horseradish peroxidase in combination with methionine-enkephalin or tyrosine hydroxylase immunocytochemistry to 1) determine the locations of pontospinal enkephalinergic neurons and 2) compare these with the locations of pontospinal catecholaminergic neurons. Pontospinal enkephalinergic neurons were observed in the nuclei locus coeruleus and subcoeruleus and the Kölliker-Fuse nucleus. A high concentration of these neurons was evident in the Kölliker-Fuse nucleus when compared to the nuclei locus coeruleus and subcoeruleus (P less than .01). Both the enkephalinergic and catecholaminergic neurons projecting to the spinal cord were located in the same general areas of the dorsolateral pontine tegmentum and there was no significant difference in the mean diameters of these two neuronal types (P greater than .05). Quantitative data concerning the pontospinal enkephalinergic neurons correlated well with previous data on pontospinal catecholaminergic neurons (Reddy et al., Brain Res. 491:144-149, '89). A majority of the descending neurons from the dorsolateral pontine tegmentum contain enkephalin (72-80%) and catecholamine (80-87%). The observations suggest that enkephalin is contained in many of the pontospinal catecholaminergic neurons.

Animals↗

Evaluation of neuron-based sensing with the neurotransmitter serotonin.

Results are presented on the development of a novel biosensor which will use neurons or neuronal components as both the recognition elements and primary transducers for analyte quantitation. This concept is demonstrated and evaluated by exposing identified neurons from the visceral ganglia of the pond snail Limnea stagnalis to the model analyte serotonin. Experiments reveal a reversible, concentration-dependent increase in the rate of spontaneous action potential generation, over a concentration range of four orders of magnitude. Studies with the antagonist methysergide verify that this response is mediated through serotonin-sensitive receptors. Exposure of the neurons to serotonin causes the firing frequency to rapidly increase to a maximum and then slowly diminish to a sub-optimal level. It was found that the maximum frequency provides an indication of chemical concentration that is repeatable. Data are also presented which further advance the field of neuronal biosensing by demonstrating both the effects of cell to cell variability on response reproducibility and the effects of the desensitizing response on the operation of a neuron-based sensor in both a continuous and discontinuous mode.

Action Potentials↗

Serotonin depolarizes cat spinal motoneurons in situ and decreases motoneuron afterhyperpolarizing potentials.

Mechanisms by which serotonin produces a long duration facilitation of spinal motoneuron excitability were investigated in decerebrate cats using intracellular recording combined with extracellular microiontophoresis. Serotonin was found to produce a slowly developing, small amplitude, long duration depolarization of the spinal motoneurons. This finding conflicts with early reports of serotonin-induced rapid hyperpolarization of cat spinal motoneurons, but exactly corresponds to more recent findings in rat facial motoneurons. The depolarization was accompanied by an increase in motoneuron excitability and an increase in membrane input resistance. In addition, serotonin reduced the motoneuron postspike afterhyperpolarizing potential in several motoneurons even through depolarization consistently occurred.

Action Potentials↗

Raphé-produced excitation of spinal cord motoneurons in the cat.

In all motoneurons examined, both flexor and extensor, raphé (pallidus) stimulation consistently produced an excitatory postsynaptic potential (EPSP). Upon interaction with a group Ia EPSP there was summation resulting in neuronal discharge. The raphé-induced EPSP also facilitated the initial segment-somadendritic coupling and hence the motoneuron excitability. These data support an excitatory role for raphé-spinal fibers on cat hindlimb motoneurons.

Action Potentials↗

Spinally projecting noradrenergic neurons of the dorsolateral pontine tegmentum: a combined immunocytochemical and retrograde labeling study.

Two to three days following injection of horseradish peroxidase (HRP) into the spinal cords of 5 cats, the animals were sacrificed and perfused, and the brainstems removed and sectioned. The sections were then processed for HRP and, immunocytochemically, for tyrosine hydroxylase (TH). The dorsolateral pontine tegmentum was divided into the locus coeruleus, subcoeruleus and Kölliker-Fuse nucleus; the mean percentage of pontospinal neurons containing TH were found to be 85.5 +/- 2.5 (S.E.M.), 79.6 +/- 5.6 and 87.1 +/- 3.1, respectively. The cell diameters of locus coeruleus cells were also measured.

Adrenergic Fibers↗

The actions of two monoamines on spinal motoneurons from stimulation of the locus coeruleus in the cat.

The present study investigates the role of the two putative amine transmitters (norepinephrine and serotonin) in mediating the facilitatory action following locus coeruleus (LC) stimulation on hindlimb flexor and extensor monosynaptic reflexes (MSRs) in unanesthetized, decerebrate cats. When administered sequentially, in either order, methysergide (a serotonergic blocker) and prazosin (an alpha 1-adrenergic blocker) were observed to cause subtotal, decremental changes in the potentiation of gastrocnemius-soleus and common peroneal MSRs by stimuli applied in the LC. These changes were determined to be independent of the blood pressure changes induced by the aminergic blockers. These results support the hypothesis that the facilitation of the group Ia reflex transmission in cat spinal cord by stimulation of LC is mediated in part by alpha 1-noradrenergic and serotonergic mechanisms.

Adrenergic Fibers↗

Coerulospinal influence on recurrent inhibition of spinal motonuclei innervating antagonistic hindleg muscles of the cat.

The locus coeruleus's (LC's) effect on recurrent inhibition of gastrocnemius-soleus (GS) and common peroneal (CP) monosynaptic reflexes (MSRs) was demonstrated to exceed the concomitant facilitation, indicating the independency of LC's disinhibition and facilitation measures in this study. In contrast, the disinhibition effect correlated closely with the recurrently inhibited MSRs. The disinhibition phenomenon was also accompanied by progressive delay and diminution in the Renshaw cell field potential. Hence, the recovery of recurrently inhibited MSRs was probably due, in part at least, to the LC's inhibition of the related Renshaw cell activity. Furthermore, the site-specific, discordant changes in the disinhibition of GS, compared with CP MSRs, as revealed by tracking studies imply that representations of these antagonistic motonuclei may occupy different LC loci. Accordingly, the nonuniform disinhibition may be due to the activation of discrete aggregates of LC neurons which are responsible predominantly in controlling the recurrent inhibitory pathway belonging to one or the other of the antagonistic motonuclei. These findings support a differential LC inhibitory control of Renshaw cell activity, releasing the related motoneurones for the Ia synaptic transmission - a disinhibitory process that is crucial for the LC's independent control of the recurrent circuit of antagonistics extensor and flexor motoneurons.

Animals↗

Serotonergic and non-serotonergic raphe neurons projecting to the feline lumbar and cervical spinal cord: a quantitative horseradish peroxidase-immunocytochemical study.

A quantitative study of raphe-spinal neurons and serotonergic neurons in 3 medullary raphe nuclei in the cat indicates that more than 80% of the raphe-spinal neurons that project to the spinal cord are serotonergic raphe-spinal neurons in each of the nuclei. More than 85% of the descending raphe-spinal neurons in the two caudal nuclei, nucleus raphe pallidus and nucleus raphe obscurus, are serotonergic, whereas 75% of the raphe-spinal neurons in the more rostrally placed nucleus raphe magnus contain serotonin (5-HT). These results are discussed in relation to descending systems containing both neuropeptides and 5-HT and collateralizing to several spinal segments.

Animals↗

Membrane excitability changes in hindlimb motoneurons induced by stimulation of the locus coeruleus in cats.

The present analysis describes the cellular mechanisms underlying the heightened membrane excitability of hindlimb flexor and extensor motoneurons upon stimulation of the locus coeruleus (LC) in unanesthetized, decerebrate cats. In a total of 73 cells, brief train stimuli to the LC at 50-300 microA intensity evoked one of 4 patterns of motoneuronal responses: a simple excitatory postsynaptic potential (EPSP) with weak trailing depolarization, a double-peak EPSP, an EPSP succeeded by a weak hyperpolarization, or a slow rising EPSP. As the initial dominant EPSP was a consistent finding among all cells and the ensuing potentials were variable in polarity, quantitative characterization was focused on the initial EPSP only. In all cells tested (n = 11), the LC-EPSP was accompanied by a decrease in input resistance. The excitatory LC action was further demonstrated by the consistent (n = 25 cells) motoneuron rheobase decrease when the latter was measured coincident with the summit of an LC-EPSP. Furthermore, the time course of the single-spike afterhyperpolarization became shortened during the LC conditioning stimuli (n = 16 motoneurons). Our data show that the descending LC action on motoneurons is typified by an EPSP accompanied by a net decrease in input resistance as well as a concurrent increase in motoneuron electrical excitability.

Animals↗

Suppression of the recurrent inhibitory pathway in lumbar cord segments during locus coeruleus stimulation in cats.

The present study revealed a consistent reduction of ventral root-induced recurrent inhibition of monosynaptic reflexes in both extensor (gastrocnemius-soleus) and flexor (common peroneal) motonuclei upon delivery of preconditioning stimuli to the locus coeruleus (LC) in decerebrate cats. The magnitudes of the LC-induced decrease in recurrent inhibition, functionally disinhibition, and of recurrent inhibition were significantly correlated. Direct recordings from Renshaw cells have indicated that LC conditioning stimuli cause a decrease in the number of spikes and the duration of firing in response to single antidromic (ventral root) volleys. These results suggest that the LC depression of the recurrent inhibitory pathway is attributed, in part at least, to inhibition of Renshaw cell activity.

Animals↗

Differential labeling of the vestibular complex following unilateral injections of horseradish peroxidase into the cat and rat locus coeruleus.

Following unilateral injections of horseradish peroxidase into the cat and rat locus coeruleus (LC), bilateral retrograde labeling was evident in all 4 vestibular nuclei. In both species, the major contributions of LC afferents arose from the ipsilateral rather than the contralateral vestibular nuclei. Quantitative analysis in the rat has indicated that approximately 90% of the total vestibular-LC projections originated from the ipsilateral vestibular nuclear complex, with 10% from the contralateral. The frequency distribution was in the order of lateral greater than medial greater than superior greater than inferior vestibular nuclei.

Animals↗

Basic electrophysiological properties of spinal cord motoneurons during old age in the cat.

1. The electrophysiological properties of alpha-motoneurons in old cats (14-15 yr) were compared with those of adult cats (1-3 yr). These properties were measured utilizing intracellular recording and stimulating techniques. 2. Unaltered in the old cat motoneurons were the membrane potential, action potential amplitude, and slopes of the initial segment (IS) and soma dendritic (SD) spikes, as well as the duration and amplitude of the action potential's afterhyperpolarization. 3. In contrast, the following changes in the electrophysiological properties of lumbar motoneurons were found in the old cats: a decrease in axonal conduction velocity, a shortening of the IS-SD delay, an increase in input resistance, and a decrease in rheobase. 4. In spite of these considerable changes in motoneuron properties in the old cat, normal correlations between different electrophysiological properties were maintained. The following key relationships, among others, were the same in adult and old cat motoneurons: membrane potential polarization versus action potential amplitude, duration of the afterhyperpolarization versus motor axon conduction velocity, and rheobase versus input conductance. 5. A review of the existing literature reveals that neither chronic spinal cord section nor deafferentation (13, 21) in adult animals produce the changes observed in old cats. Thus we consider it unlikely that a loss of synaptic contacts was responsible for the modifications in electrophysiological properties observed in old cat motoneurons. 6. We conclude that during old age there are significant changes in the soma-dendritic portion of cat motoneurons, as indicated by the modifications found in input resistance, rheobase, and IS-SD delay, as well as significant changes in their axons, as indicated by a decrease in conduction velocity.

Action Potentials↗

Coerulospinal enhancement of repetitive firing with correlative changes in postspike afterhyperpolarization of cat spinal motoneurons.

The present study was aimed at determining if inputs from the locus coeruleus (LC) have any effect on repetitive firing of ventral horn motoneurons in cats. In hindlimb flexor and extensor motoneurons stimulated intrasomatically with current below the threshold for repetitive discharges, added LC-evoked excitatory post-synaptic potentials (EPSPs) were consistently found to produce repetitive firing, suggesting a lowering in the repetitive firing threshold attributable to excitatory LC inputs. With those extensor motoneurons showing episodic, self-sustained firing, LC-EPSPs introduced during the quiescent period were capable of starting a continuous discharge with rhythmic frequencies higher than the spontaneous activity. In some of these cells, intracellularly applied hyperpolarizing current was able to stop the spontaneous discharges. Subsequently, LC stimuli were found to reinitiate repetitive discharges, thus counteracting the ongoing suppression of the motoneurons. Quantitative analysis of the single-spike afterhyperpolarization (AHP) indicated a consistent reduction in its amplitude and time course (duration, time-to-peak, half-decay time) for flexor and extensor motoneurons in response to LC conditioning stimuli. Present results suggest an excitatory LC action on the repetitive discharges of cat motoneurons accompanied by a concurrent decrease in the amplitude and time course of the single-spike AHPs.

Animals↗

Presynaptic facilitatory action of locus coeruleus stimulation upon hindlimb sensory impulse transmission in decerebrate cats.

This study sought to delineate the presynaptic role of the locus coeruleus (LC) on hindlimb primary afferent terminals. Changes in presynaptic function in response to LC stimulation were assessed by measuring the dorsal root potential (DRP), interaction of LC- and peripherally-evoked DRPs, and intraspinal afferent terminal excitability. LC stimulation in unanesthetized, decerebrate cats produced a sequence of early and late positive DRPs succeeded by a small-sized negative DRP. Conditioning the negative DRPs elicited from individual hindlimb nerve branches with LC stimuli led to a decrease in test DRPs. Similarly, there was a predominant decrease in excitability in both large muscle and cutaneous afferent terminals. These data suggest a presynaptic role of the LC in augmenting afferent impulse transmission, presumably through inhibition of tonically active interneurons having axoaxonic contacts on primary afferents; functionally, presynaptic facilitation.

Afferent Pathways↗

Effect of stimulation of the nucleus reticularis gigantocellularis on the membrane potential of cat lumbar motoneurons during sleep and wakefulness.

The present study was performed in order to determine the effect of electrical stimulation of the medullary nucleus reticularis gigantocellularis (NRGc) on the membrane potential of spinal cord motoneurons during sleep and wakefulness. Accordingly, intracellular recordings were obtained from lumbar motoneurons in unanesthetized normally respiring cats during naturally occurring states of wakefulness, quiet sleep and active sleep. Electrical stimuli applied to the NRGc evoked synaptic potentials which occurred at short latency (less than 10 ms) and did not exhibit consistent changes in their waveforms during any states of sleep or wakefulness. During wakefulness and quiet sleep, longer latency (greater than 20 ms) low-amplitude hyperpolarizing potentials occasionally followed NRGc stimulation. However, during active sleep, NRGc stimulation produced, in all motoneurons, relatively large hyperpolarizing potentials that were characterized by a mean amplitude of 3.5 +/- 0.4 mV (mean +/- S.E.M.), a mean latency-to-peak of 43.0 +/- 0.8 ms, and an average duration of 34.4 +/- 1.7 ms. These potentials were capable of blocking the generation of orthodromic spikes elicited by sciatic nerve stimulation. When anodal current or chloride was passed through the recording electrode, the hyperpolarizing potentials decreased in amplitude, and in some cases their polarity was reversed. These results indicate that the active sleep-specific hyperpolarizing potentials were inhibitory postsynaptic potentials. Thus, the NRGc possesses the capability of providing a postsynaptic inhibitory drive that is directed toward lumbar motoneurons which is dependent on the occurrence of the behavioral state of active sleep.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗