Course Of Repetitive Stimulation Research Articles

Contribution of AMPA, NMDA, and GABA(A) receptors to temporal pattern of postsynaptic responses in the inferior colliculus of the rat.

The central nucleus of the inferior colliculus (ICC) is a major site of synaptic interaction in the central auditory system. To understand how ICC neurons integrate excitatory and inhibitory inputs for processing temporal information, we examined postsynaptic responses of ICC neurons to repetitive stimulation of the lateral lemniscus at 10-100 Hz in rat brain slices. The excitatory synaptic currents mediated by AMPA and NMDA receptors and the inhibitory current mediated by GABA(A) receptors were pharmacologically isolated and recorded by whole-cell patch-clamp techniques. The response kinetics of AMPA receptor-mediated EPSCs and GABA(A) receptor-mediated IPSCs were similar and much faster than those of NMDA receptor-mediated EPSCs. AMPA EPSCs could follow each pulse of stimulation at a rate of 10-100 Hz but showed response depression during the course of repetitive stimulation. GABA(A) IPSCs could also follow stimulus pulses over this frequency range but showed depression at low rates and facilitation at higher rates. NMDA EPSCs showed facilitation and temporal summation in response to repetitive stimulation, which was most pronounced at higher rates of stimulation. GABA(A) inhibition suppressed activation of NMDA receptors and reduced both the degree of AMPA EPSC depression and the extent of temporal summation of NMDA EPSCs. The results indicate that GABA(A) receptor-mediated inhibition plays a crucial role in maintaining the balance of excitation and inhibition and in allowing ICC neurons to process temporal information more precisely.

Improvement of dy/dy dystrophic diaphragm by 3,4-diaminopyridine.

Concerns have been raised that inotropic agents may worsen function of dystrophic muscle due to structural fragility. Studies tested the hypothesis that force increments elicited by potassium (K(+)) channel blockade can be maintained during the course of repetitive stimulation. In vitro twitch force of dy/dy dystrophic mouse diaphragm was significantly lower than normal (796 versus 1271 g/cm(2)). 3,4-Diaminopyridine (DAP) increased twitch force of dystrophic diaphragm by 111 +/- 12% (P <.0001) and increased force at stimulation frequencies of 5-50 Hz by 41-77%. During fatigue-inducing stimulation, force augmentation by DAP was well maintained in dystrophic muscle throughout 25 Hz (P =.0047) and 50 Hz (P =.0059) stimulation. These findings indicate that the K(+) channel blocker DAP augments the force of dystrophic muscle to values close to that of normal muscle over a range of stimulation frequencies. Furthermore, these functional increments can be achieved without causing force to eventually deteriorate below that of untreated dystrophic muscle during fatiguing stimulation. It is possible that DAP may be useful for the clinical management of a variety of disorders causing muscle weakness.

Effects of CO2-induced acidification on the fatigue resistance of single mouse muscle fibers at 28 degrees C.

The role of reduced muscle pH in the development of skeletal muscle fatigue is unclear. This study investigated the effects of lowering skeletal muscle intracellular pH by exposure to 30% CO2 on the number of isometric tetani needed to induce significant fatigue. Isolated single mouse muscle fibers were stimulated repetitively at intervals of 4-2.5 s by using 80-Hz, 400-ms tetani at 28 degrees C in Tyrode solution bubbled with either 5 or 30% CO2. Stimulation continued until tetanic force had fallen to 40% of the initial value. Exposure to 30% CO2 caused a significant fall in intracellular pH of approximately 0.3 pH unit but did not cause any significant changes in initial peak tetanic force. During the course of repetitive stimulation, intracellular pH fell by approximately 0.3 pH unit in both normal and acidified fibers. The number of tetani needed to reduce force to 40% of the initial value was not significantly different in 5 and 30% CO2 Tyrode. The sole effect of acidosis was to reduce the rate of relaxation of force, especially in fatigued fibers. It is concluded that, at 28 degrees C, acidosis per se does not accelerate the development of fatigue during repeated tetanic stimulation of isolated mouse skeletal muscle fibers.

Habituation and Sensitization of the Acoustic Startle Response in Rats: Amplitude, Threshold, and Latency Measures

The amplitude of the acoustic startle response habituates to repetitive stimulation. The input and output of the startle system were measured to determine if the decrease in startle amplitude during repetitive stimulation is due to an increase in the startle threshold. Two experimental approaches were used in 35 Sprague–Dawley rats to probe the relationship between the input (the sound pressure level of the stimulus) and the behavioral output (startle amplitude). The results show that the minimum threshold for a response does not change during habituation; rather, the slope of the dependence of startle amplitude on stimulus level decreases. Because habituation does not influence startle threshold we propose that the site for habituation is located in the neural circuitry downstream from the site for startle threshold. Besides amplitude and threshold, as an additional parameter we measured startle latency. In general, the latency of the acoustic startle response is negatively correlated with the response amplitude. This correlation has been repeatedly shown, therefore one would expect a latency increase during the amplitude decrease caused by habituation. However, the latency of the startle reaction also decreased during the course of repetitive stimulation. According to the dual process theory of habituation, a stimulus has both a response-decreasing, i.e., habituating, as well as a response-increasing, i.e., sensitizing, influence on a behavior (Groves & Thompson, 1970). Our explanation of the present results is that startle amplitude is reduced following repetitive stimulation because it is mainly influenced by habituation; latency, however, is shortened because it is mainly influenced by sensitization.

Influence of trigeminal nasal afferents on bulbar respiratory neuronal activity

This study examined the influence of nasal trigeminal afferents, the anterior ethmoidal nerve (AEN) and posterior nasal nerves (PNN) on the spike discharges of respiratory-related neurons recorded in the ventral respiratory group (VRG) (2.6–3.5 mm lateral to the midline, from 1 mm rostral to 3 mm caudal to the obex and at depth of 2–4 mm below the dorsal surface). Electrical stimulations to the AEN and PNN were administered to 10 pentobarbital anaesthetized cats and to 8 ketamine anaesthetized, vagotomized, curarized and ventilated cats. Single shock stimulations of either nerve evoked transient and total inhibition of inspiratory activities. Expiratory-related neurons of the VRG presented three patterns of activity in response to stimulation:excitation, inhibition or inhibition followed by excitation. More generally, expiratory units are activated with a short latency. In the course of repetitive stimulation of the AEN and PNN we observed a prolongation of the spontaneous inspiratory discharge which presented transient, short inhibition in response to each shock. Most expiratory units presented a short activation which was synchronous with the transient inhibition of inspiratory activities. When repetitive stimulation provoked a sneeze-like response, we observed a progressive increase in the duration of transient inspiratory inhibition first, associated with a progressive reinforcement of transient expiratory activation. Secondarily, just before the expiratory thrust, we noted a stronger inhibition of the inspiratory activity which preceded a high-frequency (400 Hz) expiratory discharge. Nasal afferents exert a forceful excitatory effect on bulbospinal (BS) and non-bulbospinal—non-vagal (NBS-NV) expiratory cells of the VRG. The effects due to vagotomy and curarization are discussed.

Ipsilateral Pallidal Control on the Sternocleidomastoid Muscle in Cats

To elucidate the role of the basal ganglia on neck movement control and thus clarify the side of targets for stereotactic surgery of spasmodic torticollis, effects of electrical stimulation to the globus pallidus-entopeduncular nucleus complex (GP-EP) upon the activities of the sternocleidomastoid (SCM) muscle motoneurons were studied in cats. Repetitive stimulation of the ipsilateral GP-EP increased discharge rate in the majority of the SCM motoneurons, whereas contralateral GP-EP stimulation caused a decrease in discharge rate. These effects were gradually enhanced in the course of repetitive stimulation and lasted even after its cessation. Bilateral ablation of the motor and premotor cortices did not influence the effects of GP-EP stimulation. Latency studies suggested that the pallidal control of the SCM motoneuron is mediated by polysynaptic pathways on both sides; however, these same studies produced evidence of an ipsilateral oligosynaptic connection, as well. Repetitive antidromic stimulation of the accessory nerve caused a gradual increase in discharge rate of the SCM motoneurons, similar to the augmentation induced by ipsilateral GP-EP stimulation. Features of the responses indicate that the pallidal control on the neck muscles involves reverberating circuits in the brain stem and spinal cord. These experimental findings suggest that stereotactic thalamotomy of the ventrolateral nucleus for spasmodic torticollis should be performed on the side ipsilateral to the contracting SCM muscle.

Adenosine antagonists combined with 4-aminopyridine cause partial recovery of synaptic transmission in low Ca media.

Orthodromically and antidromically evoked field potentials, as well as changes in the extracellular calcium concentration [Ca2+]o were measured with ion selective/reference electrodes in area CA1 of rat hippocampal slices. Synaptic transmission was blocked by a low calcium, high magnesium medium. After cutting through the alveus, stratum pyramidale (Spyr) and part of stratum radiatum (Srad), repetitive electrical stimulation of Schaffer collaterals and commissural fibers elicited decreases of [Ca2+]o in Srad, the synaptic area, but not in Spyr, the soma layer of the pyramidal neurons. This indicates the absence of a measurable somatic Ca2+ influx due to postsynaptic activation and therefore, the decrease of [Ca2+]o in Scrad presumably reflect presynaptic Ca2+ entry. Antagonists of adenosine action such as adenosine deaminase and theophylline had no effects Ca2+ entry whereas 4-AP enhanced calcium signals in Scrad considerably. In some cases small [Ca2+]o decreases in Spyr appeared after treatment with 4-AP although field potentials did not reveal postsynaptic components. When 4-AP and antagonists of adenosine action were combined, a partial recovery of synaptic transmission was consistently seen during the course of repetitive stimulation. This was indicated by large decreases of [Ca2+]o in Spyr as well as by the generation of postsynaptic field potentials. The latter appeared late during the train pointing to frequency potentiation and a presynaptic site of action. The findings indicate that physiological levels of adenosine in the order of 1 microM have a powerful modulatory role on synaptic transmission by depressing presynaptic transmitter release. This seems to result not from an influence on presynaptic calcium uptake, but rather from changing the intracellular level of calcium or its coupling to the secretory process.

On a clocklike mechanism timing lunar-rhythmic reproduction inTyposyllis prolifera (Polychaeta)

In ‘constant’ conditions, individuals of the polychaeteTyposyllis prolifera stolonize up to 18 times each at circalunar intervals (mean ∼31 days). The endogenous mechanism driving this reproduction rhythm exhibits the characteristics of a true ‘circa’-oscillator (circalunar clock): 1. Entrainment of cyclic sexual development (and ultimately stolonial swarming) to the lunar cycle has been demonstrated both in the field and in experimental conditions. Animals in a natural population tend to reproduce synchronously during the 2nd quarter phase of the moon. In asynchronous laboratory populations, ‘moonlight’ zeitgeber programs (some successive ‘moonlit’ nights every 30 days) cause entrainment, provided that the zeitgeber signals exceed a critical length (between 2 and 4 days). Above this value, the length of zeitgeber stimuli does not affect the quality of entrainment. The peaks of stolon abundance are phase-set by the cessation of nocturnal illumination (mean at 20 °C: 17.0 days after ‘moonoff’), independent of the length of the preceding ‘moonlit’ period. The temporal pattern of increasing entrainment in the course of repetitive stimulation permits a preliminary insight into the mechanism which causes adjustment of the clock. 2. Within the range of 15 to 25 °C, the freerunning period is temperature-compensated (Q10=1.04). However, coupling between oscillator and overt rhythm is restricted to the (cyclic) initiation of stolonization processes. Stolon release follows at a temperature dependent interval. Changes in temperature thus result in phase-shifts of the overt rhythm of stolon release. 3. The oscillator runs essentially independent of the peripheral physiological processes involved in the manifestation of the reproduction rhythm (absence of feedback influences). Temperature and starvation influence the overt rhythm while the endogenous oscillator remains largely unaffected.

Parameters of a model of transmitter depletion in synapses of identified snail neurons

Unitary EPSP were recorded in two identified neurons of the snail ganglia after stimulation of an identified presynaptic neuron. Low-frequency EPSP depression was found in the course of repetitive stimulation (0.1-0.5/s). Transmitter release at two synapses was analyzed in terms of the depletion model using known and modified methods. The fraction of available pool (F) released by a presynaptic impulse was not significantly different at synapses of two different target neurons. The available pool of transmitter (C) and the rate constant of demobilization (k) in the RPa3 neuron were found to be 2-3 times and mobilization (M) 10 times as high as in the LPa2 neuron. Deviations of the depletion model from the experimental data were found. A new method was developed permitting k to be determined and any change in F to be postulated. No significant correlation was found between parameters of the depletion model F and C and the binomial parameters p and n calculated on the basis of the quantal hypothesis, which shows that the depletion model and quantal hypothesis describe different synaptic mechanisms.

Paired-pulse and frequency facilitation in the CA1 region of the in vitro rat hippocampus.

1. Several types of facilitation of evoked synaptic responses were investigated in the CA1 region of the in vitro rat hippocampus. Homosynaptic paired-pulse facilitation and heterosynaptic frequency facilitation were characterized and found to be differentiable processes on the basis of several characteristics.2. Paired-pulse facilitation, which occurs when the same input is stimulated twice in rapid succession, is manifested as an increase in both the extracellularly recorded population spike and the field e.p.s.p., and is specific to the set of afferents excited by the first impulse. Responses to other excitatory afferents show no facilitation by a heterosynaptic conditioning pulse.3. At intervals less than 200 msec, the degree of facilitation produced by a preceding impulse appears to decline as a first order exponential function of time. Facilitation is increased by lowering calcium or raising magnesium concentrations in the bathing medium, with no apparent change in the time constant of the decay process.4. The phenomenon that has sometimes been termed frequency facilitation, and which occurs during the early phase of repetitive stimulation, appears to be an extension of paired-pulse facilitation. It is seen as an increase in amplitude of both the e.p.s.p. and population spike in response to stimulation of homosynaptic inputs, can be predicted with fair accuracy by assuming that the residual paired-pulse facilitation produced by each impulse adds linearly with that from previous impulses, and is affected by calcium and magnesium ions in the same manner as is paired-pulse facilitation. These two types of facilitation, which apparently share a common mechanism, are termed synaptic or primary facilitation.5. Another type of facilitation, which we suggest might more properly be called frequency facilitation, develops slowly during the course of repetitive stimulation. It is the result of an increase in cell firing in response to any excitatory input, either homo- or heterosynaptic, at time points at which the field e.p.s.p. is typically depressed.6. Increases in the potassium concentration of the perfusion medium produce effects similar to those observed with frequency facilitation; stimulation-evoked increases in the extracellular concentration of this ion are hypothesized to underlie this type of generalized facilitation.

Electrophysiological correlates of the response decrement produced by mechanical stimuli in the protozoan, Stentor coeruleus.

AbstractThe response pattern of Stentor coeruleus has been studied using repetitive mechanical stimuli which were applied to a limited body surface. The decrement in the probability of response was found to parallel that previously reported when more gross mechanical stimuli were employed. This result justified the employment of such localized stimuli in the determination of electrophysiological correlates of the response decrement.Electrophysiological records show a decrease in the amplitude of the prepotential and an increase in the latency of the response during the course of repetitive stimulation. After considering possible complications resultant from changes in the amplitude of the diphasic potential and the relation of the stimulus probe to the animal, it was concluded that the potential changes noted do, in fact, indicate a change in receptor function is associated with the response decrement. This result was predicted on the basis of previously reported behavioral data.

Thalamo-cortical recruiting responses during sleep characterized by a low voltage fast EEG

1. 1. During sleep characterized by a low voltage fast EEG, recruiting responses could be elicited in cats in the course of repetitive stimulation of “non-specific” thalamus by using a stimulus strength slightly supraliminal for recruiting responses during sleep characterized by EEG slow waves. 2. 2. The occurrence of recruiting responses and “sustained waves” depended on the stimulus strength and the actual state of the animal. 3. 3. In the same animal the thresholds for eliciting recruiting responses during slow wave sleep and “sustained waves” during low voltage fast sleep and quiet wakefulness were about the same. There was no remarkable difference between the latencies of the “sustained” and recruiting waves during low voltage fast sleep. 4. 4. During low voltage fast sleep, recruiting responses and rapid eye movements (REMs) usually did not appear simultaneously; i.e., if stimulation was started during REMs the first recruiting response was often delayed. From another point of view, REMs did not usually start during recruiting responses. A similar relationship was found between recruiting responses and the electrical activity of the levator palpebrae superioris muscles. The decrease of the tonic component of the levator EMG was often parallel with the waxing phase of the recruiting response. In the waking state also the searching eye movements and recruiting responses did not usually occur concurrently. 5. 5. It can be assumed that during low voltage fast sleep in the course of continual repetitive stimulation, the temporal distribution of recruiting response groups corresponds to fluctuations of the low voltage fast sleep level. These fluctuations might indicate an occasional tendency to slow wave sleep.

Parametric studies of the response decrement produced by mechanical stimuli in the protozoan, Stentor coeruleus.

AbstractA decrement in the probability of eliciting a response is observed during the course of repetitive stimulation in many response systems of both metazoa and protozoa. Those forms of metazoan response decrement called habituation have recently been characterized behaviorally. In the studies reported here, the response decrement of the contractile protozoan, Stentor coeruleus, to repeated mechanical stimulation was systemically characterized to provide a comparison with metazoan habituation. This change in response probability was closely approximated by a negative exponential function after the first few stimuli. Animals responded to parametric variations of stimulus amplitude, interstimulus interval and retention period in a manner paralleling that observed in metazoa. However, neither interpolated large amplitude mechanical stimuli nor suprathreshold electrical stimuli produced dishabituation in Stentor though these stimuli are among the most effective dishabituating stimuli for metazoan tactile response systems. Behavioral analysis of the response decrement proceeded on the assumption that Stentor contains receptor and effector mechanisms only. Since the response decrement was not correlated with a change in responsiveness to electrical stimuli, the ability of the animal to contract appears to be unaltered by the process producing the response decrement. On the other hand, weak mechanical prestimuli were found to increase the rate of the response decrement which suggests that a process of receptor adaption is operative.