PubMed HealthSearch

Biomedical subjects

J S Carp

Publications and source records attributed to J S Carp.

At least 19 recordsLinked to original sources

Sag during unfused tetanic contractions in rat triceps surae motor units.

Contractile properties and conduction velocity were studied in 202 single motor units of intact rat triceps surae muscles activated by intra-axonal (or intra-myelin) current injection in L5 or L6 ventral root to assess the factors that determine the expression of sag (i.e., decline in force after initial increase during unfused tetanic stimulation). Sag was consistently detected in motor units with unpotentiated twitch contraction times <20 ms. However, the range of frequencies at which sag was expressed varied among motor units such that there was no single interstimulus interval (ISI), with or without adjusting for twitch contraction time, at which sag could be detected reliably. Further analysis indicated that using the absence of sag as a criterion for identifying slow-twitch motor units requires testing with tetani at several different ISIs. In motor units with sag, the shape of the force profile varied with tetanic frequency and contractile properties. Simple sag force profiles (single maximum reached late in the tetanus followed by monotonic decay) tended to occur at shorter ISIs and were observed more frequently in fatigue-resistant motor units with long half-relaxation times and small twitch amplitudes. Complex sag profiles reached an initial maximum early in the tetanus, tended to occur at longer ISIs, and were more common in fatigue-sensitive motor units with long half-relaxation times and large twitch amplitudes. The differences in frequency dependence and force maximum location suggested that these phenomena represented discrete entities. Successive stimuli elicited near-linear increments in force during tetani in motor units that never exhibited sag. In motor units with at least one tetanus displaying sag, tetanic stimulation elicited large initial force increments followed by rapidly decreasing force increments. That the latter force envelope pattern occurred in these units even in tetani without sag suggested that the factors responsible for sag were expressed in the absence of overt sag. The time-to-peak force (TTP) of the individual contractions during a tetanus decreased in tetani with sag. Differences in the pattern of TTP change during a tetanus were consistent with the differences in force maximum location between tetani exhibiting simple and complex sag. Tetani from motor units that never exhibited sag did not display a net decrease in TTP during successive contractions. These data were consistent with the initial force decrement of sag resulting from a transient reduction in the duration of the contractile state.

Anesthesia

Operantly conditioned motoneuron plasticity: possible role of sodium channels.

1. Learning is traditionally thought to depend on synaptic plasticity. However, recent work shows that operantly conditioned decrease in the primate H reflex is associated with an increase in the depolarization needed to fire the spinal motoneuron (VDEP) and a decrease in its conduction velocity (CV). Furthermore, the increase in VDEP appears to be largely responsible for the H-reflex decrease. The conjunction of these changes in VDEP and CV suggests that an alteration in Na+ channel properties throughout the soma and axon could be responsible. 2. A mathematical model of the mammalian myelinated axon was used to test whether a positive shift in the voltage dependence of Na+ channel activation, a decrease in Na+ channel peak permeability, or changes in other fiber properties could have accounted for the experimental findings. 3. A positive shift of 2.2 mV in Na+ channel activation reproduced the experimentally observed changes in VDEP and CV, whereas a reduction in Na+ channel permeability or changes in other fiber properties did not. 4. These results are consistent with the hypothesis that operantly conditioned decrease in the primate H reflex is largely due to a positive shift in the voltage dependence of Na+ channel activation. Recent studies suggest that change in activation of protein kinase C may mediate this effect.

Action Potentials

Motoneuron properties after operantly conditioned increase in primate H-reflex.

1. Monkeys can increase (HRup conditioning mode) or decrease (HRdown conditioning mode) the triceps surae (TS) H-reflex in response to an operant conditioning task. This conditioning modifies the spinal cord. To define this spinal cord plasticity and its role in the behavioral change (H-reflex increase or decrease), we have recorded intracellularly from TS motoneurons in conditioned animals. The present report describes data from HRup animals and compares them with data from previously studied naive (NV; i.e., unconditioned) animals. 2. Thirteen monkeys (Macaca nemestrina, male, 3.8-7.1 kg) were exposed to the HRup conditioning mode, in which reward occurred when H-reflex size in one leg (i.e., the trained leg) was above a criterion value. Conditioning was successful (i.e., increase of > or = 20%) in 12 of the 13 animals. At the end of conditioning, H-reflex size in the trained leg averaged 188% of its initial value, whereas size in the control leg averaged 134% of its initial value. 3. Intracellular recordings were obtained from 136 TS motoneurons on trained (UT + motoneurons) and control (UC + motoneurons) sides of the successful animals. Measurements included axonal conduction velocity, input resistance, time constant, electrotonic length, rheobase, firing threshold to current injection, afterhyperpolarization duration and amplitude, and composite homonymous and heteronymous excitatory postsynaptic potential (EPSP) size and shape. Results were compared with intracellular data from NV animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Motoneuron plasticity underlying operantly conditioned decrease in primate H-reflex.

1. Monkeys can gradually increase or decrease the size of the triceps surae H-reflex in response to an operant conditioning task. This conditioning modifies the spinal cord. To determine the location and nature of the spinal cord plasticity and define its role in the behavioral change (i.e., H-reflex increase or decrease) we have recorded intracellularly from triceps surae motoneurons in conditioned animals and compared the results with data from naive (i.e., unconditioned) animals. 2. Eleven monkeys (Macaca nemestrina, male) were exposed to the HRdown conditioning mode, in which reward occurred when H-reflex size in one leg (i.e., the trained leg) was below a criterion value. In six animals (5.1-8.2 kg) H-reflex size in the trained leg fell to 24-58% of its initial value, whereas in the other five animals (4.0-5.5 kg) it remained at 92-114% of its initial value. This outcome, which was in accord with recent data indicating that success in HRdown conditioning is age dependent, allowed comparison of intracellular data from successful HRdown animals with data from unsuccessful animals as well as with data from naive (i.e., unconditioned) animals. 3. Intracellular recordings were obtained from 221 triceps surae motoneurons on trained and control sides of successful and unsuccessful HRdown animals. Measurements included axonal conduction velocity, input resistance, time constant, electrotonic length, rheobase, firing threshold, afterhyperpolarization duration and amplitude, and composite homonymous and heteronymous excitatory postsynaptic potentials to peripheral nerve stimulation. Results were compared with data from 109 triceps surae motoneurons in naive animals. 4. Motoneurons from the trained side of successful HRdown animals had a significantly more positive average firing threshold (-52 vs. -55 mV) and a significantly lower average conduction velocity (67 vs. 71 m/s) than those from naive animals. In contrast, motoneurons from the trained side of unsuccessful HRdown animals were not significantly different from naive motoneurons. 5. These data are consistent with the hypothesis that operantly conditioned decrease in H-reflex size is due to a positive shift in motoneuron firing threshold and a consequent increase in the depolarization needed to reach that threshold. 6. The more positive firing threshold, if present in the axon as well as in the soma, could also account for the decreased conduction velocity observed in motoneurons from the trained side of successful animals.

Animals

Operant conditioning of the primate H-reflex: factors affecting the magnitude of change.

Primates can gradually increase or decrease H-reflex amplitude in one leg when reward depends on that amplitude. The magnitude of change varies greatly from animal to animal. This study sought to define the factors that control this magnitude. It evaluated the influence of animal age, muscle size (absolute and relative), background electromyographic activity (EMG) level, M response amplitude, initial H-reflex amplitude, performance intensity, and behavior of the contralateral leg. Fifty-four animals (Macaca nemestrina) underwent operant conditioning of the triceps surae H-reflex in one leg (the trained leg). Twenty-eight were rewarded for larger H-reflexes (HRup animals), and 26 were rewarded for smaller H-reflexes (HRdown animals). In the HRup animals, H-reflex amplitude in the trained leg rose to an average final value of 177% of its initial amplitude. Magnitude of increase varied widely across animals. Nine animals rose to 120-140%, 11 to 160-240%, three to 300% or more, and five remained within 20% of initial amplitude. In the HRdown animals, H-reflex amplitude in the trained leg decreased to an average of 69% of initial amplitude. Magnitude of decrease varied widely. Five animals decreased to 20-40%, seven to 40-60%, six to 60-80%, and eight remained within 20% of initial amplitude. Animal age, as assessed by weight, markedly affected HRdown conditioning, but not HRup conditioning. Heavy HRdown animals (> or = 6 kg) were more successful than light HRdown animals (< 6 kg). Thirteen of 14 heavy animals and only five of 12 light animals decreased to less than 80% of initial amplitude.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging

Monosynaptic EPSPs in primate lumbar motoneurons.

1. Homonymous and heteronymous monosynaptic composite excitatory postsynaptic potentials (EPSPs) were evaluated by intracellular recordings from 89 motoneurons innervating triceps surae (n = 59) and more distal (n = 30) muscles in 14 pentobarbital-anesthetized monkeys (Macaca nemestrina). 2. Homonymous EPSPs were found in all motoneurons tested. The mean values +/- SD for maximum EPSP amplitude of triceps surae motoneurons were 2.5 +/- 1.3, 1.8 +/- 1.3 and 4.5 +/- 2.0 mV for medial gastrocnemius, lateral gastrocnemius, and soleus motoneurons, respectively. Heteronymous EPSPs were almost always smaller than their corresponding homonymous EPSPs. 3. Triceps surae EPSP amplitude was larger in motoneurons with higher input resistance. However, this relationship was weak, suggesting that factors related to input resistance play a limited role in determining the magnitude of the EPSP. 4. The mean ratio +/- SD of the amplitude of the EPSP elicited by combined stimulation of all triceps surae nerves to the amplitude of the algebraic sum of the three individual EPSPs was 0.95 +/- 0.05. This ratio was greater in motoneurons with lower rheobase. 5. Some patterns of synaptic connectivity in the macaque are consistent with previously reported differences between primates and cat (e.g., heteronymous EPSPs elicited by medial gastrocnemius nerve stimulation in soleus motoneurons are small in macaque and other primates but large in cat). However, no overall pattern emerges from a comparison of the similarities and differences in EPSPs among species in which they have been studied (i.e., macaque, baboon, and cat). That is, there are no two species in which EPSP properties are consistently similar to each other, but different from those of the third species.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials

The volitional nature of the simplest reflex.

Recent studies suggest that none of the behaviors of the vertebrate CNS are fixed responses incapable of change. Even the simplest reflex of all, the two-neuron, monosynaptic spinal stretch reflex (SSR), undergoes adaptive change under appropriate circumstances. Operantly conditioned SSR change occurs gradually over days and weeks and is associated with a complex pattern of CNS plasticity at both spinal and supraspinal sites.

Animals

Constancy of motor axon conduction time during growth in rats.

Axon conduction distance, conduction velocity, and conduction time were measured for individual triceps surae motoneurons in Sprague-Dawley rats weighing 230-630 g (i.e., age range 6-16 weeks). Both conduction distance (nerve length) and velocity were closely correlated with weight (r = 0.95 and r = 0.82, respectively). In contrast, conduction time did not change as weight increased nearly threefold. This striking constancy is probably due to a corresponding increase in axon diameter. It could contribute to maintenance of stable motor performance during rapid growth.

Animals

Physiological properties of primate lumbar motoneurons.

1. Intracellular recordings were obtained from 149 motoneurons innervating triceps surae (n = 109) and more distal muscles (n = 40) in 14 pentobarbital-anesthetized monkeys (Macaca nemestrina). The variables evaluated were resting membrane potential, action potential amplitude, conduction velocity (CV), input resistance (RN), membrane time constant (tau m), electrotonic length (L), whole-cell capacitance (Ctot), long current pulse threshold (rheobase), short current pulse threshold (Ishort), afterhyperpolarization (AHP) maximum amplitude (AHPmax), AHP duration (AHPdur), time to half maximum AHP amplitude (AHP t1/2), depolarization from resting potential to elicit action potential (Vdep), and threshold voltage for action potential discharge (Vthr). 2. Mean values +/- SD for the entire sample of motoneurons are as follows: resting membrane potential -67 +/- 6 mV; action potential amplitude 75 +/- 7 mV; CV 71 +/- 6 m/s; RN 1.0 +/- 0.5 M omega; tau m 4.4 +/- 1.5 ms; L 1.4 +/- 0.2 lambda; Ctot 7.1 +/- 1.8 nF; rheobase 13 +/- 7 nA; Ishort 29 +/- 14 nA; AHPmax 3.5 +/- 1.3 mV; AHPdur 77 +/- 26 ms; AHP t 1/2 21 +/- 7 ms; Vdep 11 +/- 4 mV; and Vthr -56 +/- 5 mV. CV is lower in soleus than in either medial or lateral gastrocnemius motoneurons, and RN is lower and tau m is longer in soleus than in lateral gastrocnemius motoneurons. 3. RN is higher in motoneurons with longer tau m and slower CV. A linear relationship exists between log(CV) and log(1/RN) with a slope of 1.8-2.2 (depending on the action potential amplitude acceptance criteria used), suggesting that membrane resistivity (Rm) does not vary systematically with cell size. 4. Rheobase is higher in motoneurons with lower RN, longer tau m, shorter AHP time course, and higher CV. Ishort and normalized rheobase (i.e., rheobase/Ctot) vary similarly with these motoneuron properties, except that Ishort is independent of tau m and normalized rheobase is independent of CV. 5. Vthr tends to be more depolarized in motoneurons with large Ctot, but the relationship is sufficiently weak so that any systematic variation in Vthr according to cell size probably contributes only minimally to recruitment order. Vthr does not vary systematically with CV, AHP time course, RN, or tau m. 6. Quantitative differences between macaque and cat triceps surae motoneurons are apparent in CV, which is slower in macaque than in cat, and to a lesser extent in tau m and RN, which are lower in macaque than in cat.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials

Alterations in motoneuron properties induced by acute dorsal spinal hemisection in the decerebrate cat.

Using intracellular recording techniques, we studied the response characteristics of two separate populations of triceps surae motoneurons in unanesthetized decerebrate cats, recorded before and after low thoracic hemisection of the spinal cord. In each preparation, we studied the response properties of one group of motoneurons and the protocol was then repeated for a separate group, immediately following the dorsal hemisection. In each group, we examined both the minimum firing rates of motoneurons during intracellular current injection and a range of cellular properties, including input resistance, rheobase current and afterhyperpolarization time course and magnitude. Although earlier studies from this laboratory have shown substantial reductions in minimum firing rate in reflexively active motoneurons in the hemisected decerebrated preparation, the response of motoneurons to intracellular current injection in the current preparation proved to be quite different. Minimum firing rates were either normal or even somewhat higher in the post-lesion group, while the time course of the afterhyperpolarization was shortened. Moreover, these effects were not evenly distributed across the motoneuron pool. The rate effect was most evident in motoneurons with higher conduction velocity, while the afterhyperpolarization effect occurred predominantly in motoneurons with lower conduction velocity. Neither of these effects could be accounted for by lesion-induced changes in other cellular properties. We conclude that tonically active neurons with descending axons traversing dorsolateral white matter may influence both the discharge characteristics and membrane properties of spinal motoneurons in novel ways, presumably by modifying voltage or calcium activated motoneuronal conductances. The previously described reactions in the firing rate of motoneurons after such lesions appear to be mediated by different means, perhaps by alterations in synaptic input from segmental interneurons.

Action Potentials

Operantly conditioned plasticity in spinal cord.

Recent work has shown that the monosynaptic pathway of the SSR can be operantly conditioned, and that a significant part of the plasticity responsible for the behavioral change resides in the spinal cord. The most likely sites of this activity-driven plasticity are the synapse of the Ia afferent neuron on the motoneuron and/or the motoneuron itself. Because the SSR pathway is the simplest and most accessible stimulus-response pathway in the vertebrate CNS, it may provide a valuable experimental model for elucidating activity-driven CNS changes responsible for learning.

Animals

Memory traces in spinal cord.

The complexity and inaccessibility of the vertebrate CNS impede the localization and description of memory traces and the definition of the processes that create them. Recent work has shown that the spinal stretch reflex (SSR), which is produced by a monosynaptic two-neuron pathway, can be operantly conditioned, and that memory traces responsible for this behavioral change reside in the spinal cord. The probable locations are the terminal of the Ia affernt neuron on the motoneuron and/or the motoneuron itself. Because it modifies a simple well-defined and accessible pathway, SSR conditioning may be a valuable experimental model for studying vertebrate memory.

Animals

Memory traces in spinal cord produced by H-reflex conditioning: effects of post-tetanic potentiation.

Operant conditioning of the wholly spinal, largely monosynaptic triceps surae H-reflex in monkeys causes changes in lumbosacral spinal cord that persist after removal of supraspinal influence. We evaluated the interaction between post-tetanic potentiation and these memory traces. Animals in which the triceps surae H-reflex in one leg had been increased or decreased by conditioning were deeply anesthetized, and monosynaptic reflexes to L6-S1 dorsal root stimulation were recorded before and after tetanization from both legs for 3 days after thoracic cord transection. Animals remained anesthetized throughout and were sacrificed by overdose. Reflex asymmetries consistent with the effect of H-reflex conditioning were present after transection and persisted through the 3 days of study. Tetanization affected conditioned leg and control leg reflexes similarly. This finding suggests that, while post-tetanic potentiation and probably H-reflex conditioning alter Ia synaptic transmission, the two phenomena have different mechanisms.

Animals

Prevention of phencyclidine-induced depression of the segmental reflex by L-3,4-dihydroxyphenylalanine in the rat spinal cord in vitro.

The interaction between phencyclidine (PCP) and the catecholamine precursor L-3,4-dihydroxyphenylalanine (DOPA) was studied in the isolated spinal cord from neonatal rats. PCP decreased the magnitude of the dorsal-ventral reflex and enhanced frequency-dependent depression of the reflex in a concentration-dependent manner. Although DOPA and DL-threo-3,4-dihydroxyphenylserine (a direct precursor for norepinephrine) had no effect on the reflex by themselves, DOPA, but not DL-threo-3,4-dihydroxyphenylserine prevented the depression of the reflex response by PCP in a concentration-dependent manner. Inhibition of aromatic-L-amino-acid decarboxylase (EC 4.1.1.2A) by m-hydroxybenzylhydrazine markedly attenuated the action of DOPA in preventing the depression caused by PCP. The dopamine receptor antagonists haloperidol and chlorpromazine blocked the action of DOPA, but the alpha and beta adrenergic receptor antagonists phentolamine and timolol, respectively, did not. In addition, prior treatment of neonatal rats with 6-hydroxydopamine diminished the ability of DOPA to prevent the depressant effect of PCP whereas partially attenuating the depressant effect of PCP alone. These results suggest that DOPA attenuated PCP-induced depression of spinal cord transmission through its conversion to dopamine rather than norepinephrine.

Animals

Enhancement by serotonin of tonic vibration and stretch reflexes in the decerebrate cat.

The effects of pharmacological manipulation of serotonergic systems on spinal reflexes were determined in the unanesthetized decerebrate cat. The prolonged motor output that continues after cessation of high frequency longitudinal tendon vibration was strongly enhanced by the serotonin reuptake blocker fluoxetine and the serotonin precursor 5-hydroxytryptophan, and was decreased by the serotonin receptor antagonist methysergide. In addition, both dynamic and static stretch reflex stiffness was markedly increased by fluoxetine and 5-hydroxytryptophan, while methysergide produced a decrease in stretch reflex stiffness. These powerful effects on tonic vibration and stretch reflexes could not be explained by drug-induced alterations in muscle spindle primary afferent discharge. In light of other recent results on serotonin-mediated effects on motoneurons, we believe that the effects of these agents result from modification of an intrinsically mediated prolonged depolarization of spinal neurons. However, the possibility that these drugs modify longlasting discharge in associated interneuronal pathways cannot be ruled out.

Animals

Electrophysiological and biochemical studies on enhancement of desensitization by phenothiazine neuroleptics.

The actions of the phenothiazines chlorpromazine, prochlorperazine, and trifluoperazine were studied on the acetylcholine receptor-ionic channel complex of frog and rat skeletal muscle and of Torpedo californica to determine their role in pharmacological desensitization and their interactions with different states of the receptor-ionic channel complex. The phenothiazines depressed the peak amplitude of spontaneous and evoked endplate currents while having negligible effect on the decay time constants. Mean channel lifetime and single channel conductance were not altered by these drugs. They also produced a frequency-dependent depression of the peak amplitude of endplate potentials evoked by repetitive microiontophoresis at the extrajunctional region. In addition, these drugs enhanced the ability of carbamoylcholine to displace 125I-labeled alpha-bungarotoxin from receptor-rich membrane preparations of T. californica when used in concentrations that had no effect on 125I-labeled alpha-bungarotoxin binding alone (10 microM). Similarly, the phenothiazines inhibited the binding of tritiated ionic channel ligands, such as phencyclidine and perhydrohistrionicotoxin, a process also enhanced by the presence of carbamoylcholine. These data suggest that the phenothiazines augment agonist-induced desensitization primarily by interacting with the receptor-ionic channel complex prior to channel opening.

Acetylcholine