Modulation of signal transmission by the septal neurons of the rabbit during action on the cholinergic system

The neurons of the medial septum-diagonal band complex (MS-DB) were examined extracellularly in chronic unanaesthetized rabbits. Low-frequency (3-21 Hz) electrical stimulation was applied to the medial forebrain bundle within the horizontal limb of DB. In a group of the MS-DB units with stable background theta bursts the typical response consisting of entrainment of the phase-locked theta cycles was changed neither by physostigmine, nor by cholinergic-blocking drugs (scopolamine and atropine). In major group of the MS-DB units (60%), physostigmine completely blocked effects of electrical stimulation. This occurred both in the units with entrainment of the theta cycles and in the units with the effects of primary suppression of activity or (to a lesser extent) with single-spike discharges following the repetitive stimuli up to high frequencies. The cholinergic-blocking drugs restored and sometimes increased the initial reactivity of the MS-DB units. It is suggested, that intraseptal cholinergic system exerts a powerful gating effect upon transmission of signals to the hippocampus, probably, by the mechanisms of presynaptic inhibition.     

Frequency-dependent response of SI RA-class neurons to vibrotactile stimulation of the receptive field

Three types of experiment were carried out on anesthetized monkeys and cats. In the first, spike discharge activity of rapidly adapting (RA) SI neurons was recorded extracellularly during the application of different frequencies of vibrotactile stimulation to the receptive field (RF). The second used the same stimulus conditions to study the response of RA-I (RA) cutaneous mechanoreceptive afferents. The third used optical intrinsic signal (OIS) imaging and extracellular neurophysiological recording methods together, in the same sessions, to evaluate the relationship between the SI optical and RA neuron spike train responses to low- vs high-frequency stimulation of the same skin site. RA afferent entrainment was high at all frequencies of stimulation. In contrast, SI RA neuron entrainment was much lower on average, and was strongly frequency-dependent, declining in near-linear fashion from 6 to 200 Hz. Even at 200 Hz, however, unambiguous frequencyfollowing responses were present in the spike train activity of some SI RA neurons. These entrainment results support the "periodicity hypothesis" of Mountcastle et al. ( J Neurophysiol 32: 452-484, 1969) that the capacity to discriminate stimulus frequency over the range 5-50 Hz is attributable to the ability of SI RA pyramidal neurons to discharge action potentials in consistent temporal relationship to stimulus motion, and raise the possibility that perceptual frequency discriminative capacity at frequencies between 50 and 200 Hz might be accounted for in the same way. An increase in vibrotactile stimulus frequency within the range 6-200 Hz consistently resulted in an increase in RA afferent mean spike firing rate (M FR). SI RA neuron M FR also increased as frequency increased between 6 and 50 Hz, but declined as stimulus frequency was increased over the range 50-200 Hz. At stimulus frequencies > 100 Hz, and at positions in the RF other than the receptive field center (RF center ), SI RA neuron MFR declined sharply within 0.5-2s of stimulus onset and rebounded transiently upon stimulus termination. In contrast, when the stimulus was applied to the RF center, MFR increased with increasing frequency and tended to remain well maintained throughout the period of high-frequency stimulation. The evidence obtained in "combined" OIS imaging and extracellular microelectrode recording experiments suggests that SI RA neurons with an RF center that corresponds to the stimulated skin site occupy small foci within the much larger SI region activated by same-site cutaneous flutter stimulation, while for the RA neurons located elsewhere in the large SI region activated by a flutter stimulus, the stimulus site and RF center are different.     

Activity-dependent modulation of adaptation produces a constant burst proportion in a model of the lamprey spinal locomotor generator

The neuronal network underlying lamprey swimming has stimulated extensive modelling on different levels of abstraction. The lamprey swims with a burst frequency ranging from 0.3 to 8–10 Hz with a rostro-caudal lag between bursts in each segment along the spinal cord. The swimming motor pattern is characterized by a burst proportion that is independent of burst frequency and lasts around 30%–40% of the cycle duration. This also applies in preparations in which the reciprocal inhibition in the spinal cord between the left and right side is blocked. A network of coupled excitatory neurons producing hemisegmental oscillations may form the basis of the lamprey central pattern generator (CPG). Here we explored how such networks, in principle, could produce a large frequency range with a constant burst proportion. The computer simulations of the lamprey CPG use simplified, graded output units that could represent populations of neurons and that exhibit adaptation. We investigated the effect of an active modulation of the degree of adaptation of the CPG units to accomplish a constant burst proportion over the whole frequency range when, in addition, each hemisegment is assumed to be self-oscillatory. The degree of adaptation is increased with the degree of stimulation of the network. This will make the bursts terminate earlier at higher burst rates, allowing for a constant burst proportion. Without modulated adaptation the network operates in a limited range of swimming frequencies due to a progressive increase of burst duration with increasing background stimulation. By introducing a modulation of the adaptation, a broad burst frequency range can be produced. The reciprocal inhibition is thus not the primary burst terminating factor, as in many CPG models, and it is mainly responsible for producing alternation between the left and right sides. The results are compared with the Morris-Lecar oscillator model with parameters set to produce a type A and type B oscillator, in which the burst durations stay constant or increase, respectively, when the background stimulation is increased. Here as well, burst duration can be controlled by modulation of the slow variable in a similar way as above. When oscillatory hemisegmental networks are coupled together in a chain a phase lag is produced. The production of a phase lag in chains of such oscillators is compared with chains of Morris-Lecar relaxation oscillators. Models relating to the intact versus isolated spinal cord preparation are discussed, as well as the role of descending inhibition. Received: 1 April 1997 / Accepted in revised form: 20 March 1998     

Effects of Frequency and Pattern of Medial Forebrain Bundle Stimulation on Caudate Dialysate Dopamine and Serotonin

In vivo microdialysis was employed to detect changes in extracellular dopamine and serotonin in the rat caudate in response to electrical stimulation of the medial forebrain bundle. Extracellular dopamine concentrations increased linearly as a function of the frequency (4-33 Hz) of evenly spaced stimuli in both the presence and absence of cocaine added to the dialysate. Because dopamine neurons are known to fire in single-spike and burst patterns, stimulation pulses were also delivered in a bursting pattern. The response of extracellular dopamine was augmented in both the presence and absence of cocaine when the same number of stimuli were delivered in bursts as compared to an evenly spaced pattern. Serotonin, which was only assessed in the presence of cocaine, similarly increased linearly with frequency, but, in contrast to the dopamine response, levels of serotonin were not augmented by stimuli presented in bursts. These results suggest that microdialysis can be used to detect physiological changes in synaptic transmitter concentrations.     

The effect of stimulus type and background noise on hearing abilities of the round goby Neogobius melanostomus

The auditory abilities of the round goby Neogobius melanostomus were quantified using auditory evoked potential recordings, using tone bursts and conspecific call stimuli. Fish were tested over a range of sizes to assess effects of growth on hearing ability. Tests were also run with and without background noise to assess the potential effects of masking in a natural setting. Neogobius melanostomus detected tone bursts from 100 to 600 Hz with no clear best frequency in the pressure domain but were most sensitive to 100 Hz tone stimuli when examined in terms of particle acceleration. Responses to a portion of the N. melanostomus call occurred at a significantly lower threshold than responses to pure tone stimulation. There was no effect of size on N. melanostomus hearing ability, perhaps due to growth of the otolith keeping pace with growth of the auditory epithelium. Neogobius melanostomus were masked by both ambient noise and white noise, but not until sound pressure levels were relatively high, having a 5-10 dB threshold shift at noise levels of 150 dB re 1 μPa and higher but not at lower noise levels.     

Catchlike property of rat diaphragm: subsequent train frequency effects in variable-train stimulation.

A high-frequency burst of pulses at the onset of a subtetanic train of stimulation allows skeletal muscle to hold force at a higher level than expected from the extra pulses alone because of the catchlike property of muscle. The present study tested the hypothesis that the presence and degree of force increase induced by a high-frequency burst are strongly modulated by the subsequent train frequency. Rat diaphragm muscle strips (studied in vitro at 37 degrees C) underwent two-, three-, or four-pulse bursts [interpulse interval (IPI) of 5 or 10 ms] at the onset of 10- to 50-Hz subtetanic trains. Force was quantified during the train with respect to its peak value (F(peak)), mean value (F(mean)), and force-time integral (F(area)), and it was compared with that produced during subtetanic trains of an equal number of pulses without preceding pulse bursts (Diff-F(peak), Diff-F(mean), Diff-F(area)). F(peak) and F(mean) increased with two-, three-, and four-pulse bursts, and Diff-F(peak) and Diff-F(mean) increased progressively with decreasing frequency of the subtetanic train. F(area), the best reflection of catchlike force augmentation, was increased mainly by the four-pulse bursts with an IPI of 10 ms, and Diff-F(area) was maximal at subsequent train frequencies of 15-25 Hz. The use of incorrect patterns of burst stimulation could also precipitate F(area) decreases, which were observed with the four-pulse, 5-ms IPI paradigm. The time required to reach 80% of maximal force (T(80%)) became shorter for each of the pulse burst stimulation patterns, with maximal reduction of Diff-T(80%) occurring at a subsequent train frequency of 20 Hz in all cases. These data indicate that extra-pulse burst stimulation paradigms need to incorporate the optimal combinations of extra-pulse number, IPI, and the frequency of the subsequent subtetanic train to take greatest advantage of the catchlike property of muscle.     

Phase-Dependent Effects of Stimuli Locked to Oscillatory Activity in Cultured Cortical Networks

The archetypal activity pattern in cultures of dissociated neurons is spontaneous network-wide bursting. Bursts may interfere with controlled activation of synaptic plasticity, but can be suppressed by the application of stimuli at a sufficient rate. We sinusoidally modulated (4 Hz) the pulse rate of random background stimulation (RBS) and found that cultures were more active, burst less frequently, and expressed oscillatory activity. Next, we studied the effect of phase-locked tetani (four pulses, 200 s⁻¹) on network activity. Tetani were applied to one electrode at the peak or trough of mRBS stimulation. We found that when tetani were applied at the peak of modulated RBS (mRBS), a significant potentiation of poststimulus histograms (PSTHs) occurred. Conversely, tetani applied at the trough resulted in a small but insignificant depression of PSTHs. In addition to PSTHs, electrode-specific firing rate profiles within spontaneous bursts before and after mRBS were analyzed. Here, significant changes in firing rate profiles were found only for stimulation at the peak of mRBS. Our study shows that rhythmic activity in culture is possible, and that the network responds differentially to strong stimuli depending on the phase at which they are delivered. This suggests that plasticity mechanisms may be differentially accessible in an oscillatory state.     

Frequency modulation of theta bursts of the septal neurons in the removal of ascending afferent effects in rabbits

Medial septal-diagonal band (MS-DB) units were examined extracellularly in chronic rabbits under two experimental conditions: 1) in an intact septum, under anaesthetic doses of pentobarbital (40 mg/kg, i.v.); 2) in a basally undercut septum of unanaesthetized rabbits. The background rhythmic burst activity was undistinguishable in both states. Low-frequency electric stimulation of afferent inputs (MFB, CA1, LS) led to entrainment of the theta-cycles. The upper limit of following was almost normal in the undercut septum, but was strongly reduced under pentobarbital. In units with the driving "by pause", the duration of the initial silent period under pentobarbital was increased almost twofold but in the basally undercut septum it was the same as in the normal state. Some MS-DB units with weak or absent theta-modulation reacted to stimulation by stimulus-locked single spike discharges which followed up to high frequencies in both conditions.     

Modulation of Hydra attenuata rhythmic activity. Photic stimulation.

We investigated in Hydra attenuata the possibility of altering more or less permanently and in different environmental conditions, the frequency of Contraction Pulse Trains (CPT's) associated with the rhythmic spontaneous contraction activity, by repetitive light stimuli of variable duration, frequency and amplitude. The CPT's activity of various pieces of Hydra has been also investigated in indisturbed conditions and under stimulation. The following observations have been performed. 1. A transient effect, consisting of an increase or a decrease of CPT's frequency, occurs respectively after an abrupt decrease or increase of the light level. 2. If Hydra is stimulated by repetitive light pulses of 0.5-10 sec duration, at a frequency different from the CPT's average one, the CPT's frequency modifies; if the stimulation frequency is included in a range not too much up or below that of CPT's the new CPT's frequency equals exactly that of stimulation; close to this range the CPT's frequency is a multiple or submultiple of that of stimulation. 3. No habituation to such repetitive stimulation was found. 4. The phase relation between CPT's at the new frequency and light stimuli is a function of the difference between CPT's and stimulation frequencies. 5. Stimulation with repetition of light and darkness periods of some minutes duration induces activity only or mainly during darkness. 6. Modification of CPT's frequency by means of repetitive light stimulation [of the type mentioned either in 2) or 5)] has been observed also with hypostomal preparations. 7. With cessation of the light stimulation, the new CPT's frequency of the whole animal lasts in darkness for a time (10-85 min) that is about 5-10 times longer than that necessary to obtain CPT's syncronization with stimulation. 8. The influence of the light intensity level on transient CPT's frequency variation (see 1), CPT's inhibition and stimulation, promptness of entrainment, range of entrainability, phase relation between entrained CPT's and stimuli, retention time of entrained rhythm has been examined, together with the influence of the reversal of polarity of light transitions on CPT's inhibition and entrainment.     

Effects of acoustic stimuli on neuronal activity in the auditory cortex of the rat

Spontaneous activity of cortical neurons exhibits alternative fluctuations of membrane potential consisting of phased depolarization called "up-state" and persistent hyperpolarization called "down-state" during slow wave sleep and anesthesia. Here, we examined the effects of sound stimuli (noise bursts) on neuronal activity by intracellular recording in vivo from the rat auditory cortex (AC). Noise bursts increased the average time in the up-state by 0.81+/-0.65 s (range, 0.27-1.74 s) related to a 10 s recording duration. The rise times of the spontaneous up-events averaged 69.41+/-18.04 ms (range, 40.10-119.21 ms), while those of the sound-evoked up-events were significantly shorter (p<0.001) averaging only 22.54+/-8.81 ms (range, 9.31-45.74 ms). Sound stimulation did not influence ongoing spontaneous up-events. Our data suggest that a sound stimulus does not interfere with ongoing spontaneous neuronal activity in auditory cortex but can evoke new depolarizations in addition to the spontaneous ones.     

‘Communication’ in weakly electric fish, Gnathonemus niger (Mormyridae) I. Variation of electric organ discharge (EOD) frequency elicited by controlled electric stimuli

The weakly electric fish, Gathonemus niger, discharged with a frequency of 4 to 8 Hz during the day and 10 to 16 Hz during the night. The frequency of superimposed burst discharges (32 to 56 Hz) was independent of diurnal factors. The variation of the electric organ discharge frequency during the day was investigated in response to controlled electric stimulus patterns: (a) A free running stimulus frequency of 4 Hz, simulating the resting frequency of another fish, and different stimulus intensities, simulating different distances between two fish. (b) Free running frequencies of 4, 8, 16, …, 128 Hz and two particular stimulus intensities. (c) Discharge coupled stimuli (each discharge triggered an electric stimulus with a fixed delay) and different stimulus intensities.All three kinds of stimuli elicited defined and predictable response discharge patterns supporting the assumption that an electric fish would respond to a particular discharge pattern of another fish also in a similar and predictable manner. Low stimulus intensities (0·04 to 0·2 mV per cm) caused cessation of the discharge activity, a ‘hiding’ or ‘listening’ response. The discharge rate increased linearly with the logarithm of the stimulus intensity. The fish was particularly sensitive to stimulus frequencies which simulated its burst activity (32 to 56 Hz). Discharge coupled stimuli showed that the fish responded to about eight times lower stimulus intensities if the stimulus occurred between two discharges (15 to 30 m-s after the fish's discharge) than if the stimulus occurred within or immediately after the discharge. All suprathreshold stimuli elicited a typical discharge pattern: The irregular resting discharge activity became significantly regular. The degree of regularity was even improved during maintained stimulation. The regularisation of the discharge activity is thought to be involved in the fish's electrolocating system whereas frequency variations are considered as being involved in both the locating system and as communication signals among weakly electric fish.     

Vagal feedback in the entrainment of respiration to mechanical ventilation in sleeping humans.

We studied the capacity of four "normal" and six lung transplant subjects to entrain neural respiratory activity to mechanical ventilation. Two transplant subjects were studied during wakefulness and demonstrated entrainment indistinguishable from that of normal awake subjects. We studied four normal subjects and four lung transplant subjects during non-rapid eye movement (NREM) sleep. Normal subjects entrained to mechanical ventilation over a range of ventilator frequencies that were within +/-3-5 breaths of the spontaneous respiratory rate of each subject. After lung transplantation, during which the vagi were cut, subjects did demonstrate entrainment during NREM sleep; however, entrainment only occurred at ventilator frequencies at or above each subject's spontaneous respiratory rate, and entrainment was less effective. We conclude that there is no absolute requirement for vagal feedback to induce entrainment in subjects, which is in striking contrast to anesthetized animals in which vagotomy uniformly abolishes entrainment. On the other hand, vagal feedback clearly enhances the fidelity of entrainment and extends the range of mechanical frequencies over which entrainment can occur.     

A high-density EEG investigation into steady state binaural beat stimulation

Binaural beats are an auditory phenomenon that has been suggested to alter physiological and cognitive processes including vigilance and brainwave entrainment. Some personality traits measured by the NEO Five Factor Model have been found to alter entrainment using pulsing light stimuli, but as yet no studies have examined if this occurs using steady state presentation of binaural beats for a relatively short presentation of two minutes. This study aimed to examine if binaural beat stimulation altered vigilance or cortical frequencies and if personality traits were involved. Thirty-one participants were played binaural beat stimuli designed to elicit a response at either the Theta (7 Hz) or Beta (16 Hz) frequency bands while undertaking a zero-back vigilance task. EEG was recorded from a high-density electrode cap. No significant differences were found in vigilance or cortical frequency power during binaural beat stimulation compared to a white noise control period. Furthermore, no significant relationships were detected between the above and the Big Five personality traits. This suggests a short presentation of steady state binaural beats are not sufficient to alter vigilance or entrain cortical frequencies at the two bands examined and that certain personality traits were not more susceptible than others.     

Intracellular responses of antennal chordotonal sensilla of the American cockroach

The responses of mechanoreceptor neurons in the antennal chordotonal organ have been examined in cockroaches by intracellular recording methods. The chordotonal organ was mechanically stimulated by sinusoidal movement of the flagellum. Stimulus frequencies were varied between 0.5 and 150 Hz. Receptor neurons responded with spike discharges to mechanical stimulation, and were classed into two groups from plots of their average spike frequencies against stimulus frequency. Neurons in one group responded to stimulation over a wide frequency range (from 0.5 to 150 Hz), whereas those in a second group were tuned to higher frequency stimuli. The peak stimulus frequency at which receptor neurons showed maximum responses differed from cell to cell. Some had a peak response at a stimulus frequency given in the present study (from 0.5 to 150 Hz), whereas others were assumed to have peak responses beyond the highest stimulus frequency examined. The timing for the initiation of spikes or of a burst of spikes plotted against each stimulus cycle revealed that spike generation was phase-locked in most cells. Some cells showed phase-independent discharges to stimulation at lower frequency, but increasing stimulus frequencies spike initiation began to assemble at a given phase of the stimulus cycle. The response patterns observed are discussed in relation to the primary process of mechanoreception of the chordotonal organ.     

Excessive reflexes in spinal cord injury triggered by electrical stimulation

Interaction of electrocutaneous stimulation with an impaired human motor control system may result in unstable reflex loops causing excessive spastic reactions. These contractions are usually excluded from analysis since the presence of spasm is one of the criteria commonly applied for discarding a contraction. They may, however, provide interesting information on the nature of spasticity. The dorsiflexor muscles of four SCI subjects were activated by means of surface electrical stimulation and the isometric ankle moment was measured. Short bursts of constant stimulation frequency at seven different frequencies (8, 12, 16, 20, 25, 33, 50 Hz) triggered spastic reactions in all subjects. The onset times of spastic activity during an electrically elicited contraction shortened with increased stimulation frequency. A stimulation burst may also have a spasticity reduction effect on a subsequent burst, indicating potential short term therapeutic effects of stimulation on spasticity in isometric conditions.     

On the synchrony of steady state visual evoked potentials and oscillatory burst events

In this paper, we investigate the large-scale synchrony of EEG oscillatory bursts, during stimulation by a flickering square of light. Whereas most studies focus on averaged raw EEG responses, this study considers oscillatory events within EEG of single trials, which leads to various new insights. We recorded EEG signals before, during and after stimulation by a flickering square of light in medium (16 Hz) and high frequency (32 Hz) ranges. Similar oscillatory bursts, to those observed in spontaneous EEG, can be found in single-trial synchrony of steady state visual evoked potentials (SSVEP). These bursts are extracted from the EEG of single trials using bump modeling. Stochastic event synchrony method is applied to those events, which quantifies synchronies of oscillatory bursts on a large-scale basis. Those oscillatory patterns have a significantly higher degree of co-occurrence during SSVEP, uncorrelated with ongoing signal synchrony. It means that EEG oscillatory patterns are presumably an outcome of brain activity, rather than a mere side effect of ongoing EEG. They undergo a consistent reorganization during visual stimulation, preferentially along the visual pathway, depending on magno or parvo stimulations. Flickering stimuli may induce some cognitive side-effects depending on the stimulation frequency.

Temporal interaction between single spikes and complex spike bursts in hippocampal pyramidal cells

Cortical pyramidal cells fire single spikes and complex spike bursts. However, neither the conditions necessary for triggering complex spikes, nor their computational function are well understood. CA1 pyramidal cell burst activity was examined in behaving rats. The fraction of bursts was not reliably higher in place field centers, but rather in places where discharge frequency was 6-7 Hz. Burst probability was lower and bursts were shorter after recent spiking activity than after prolonged periods of silence (100 ms-1 s). Burst initiation probability and burst length were correlated with extracellular spike amplitude and with intracellular action potential rising slope. We suggest that bursts may function as "conditional synchrony detectors," signaling strong afferent synchrony after neuronal silence, and that single spikes triggered by a weak input may suppress bursts evoked by a subsequent strong input.     

The role of stimulation parameters of sympathetic nerves in regulation of microvessel tone in the rat stomach]

Maximal responses to splanchnic nerve stimulation occurred in rats at the pulse width 0.5-1.0 Ohms regardless of the frequency. Peak constriction of arterioles and venules occurred at a 3-4-sec burst duration and 1-2-sec interval. Adrenergic blockade abolished the vasoconstriction in response to continuous nerve stimulation. However, the responses persisted in high-frequency burst stimulation, suggesting an involvement of non-adrenergic co-transmitter release. Thereupon, an efficient control of microvascular tone can be achieved by grouping the pulses into bursts or by an increase of the burst rate or duration.