Sustained Excitation Research Articles

Initiation of swimming activity by trigger neurons in the leech subesophageal ganglion. II. Role of segmental swim-initiating interneurons.

Cell Tr1, a trigger neuron found in the subesophageal ganglion of the leech, Hirudo medicinalis, is part of a network of subesophageal ganglion neurons which control swimming activity, and makes apparently direct connections to swim-initiating interneurons (SIIs; cells 204 and 205). In this study, we investigated the role of SIIs in swim initiation by cell Tr1. We also examined how brief Tr1 activity controls swim initiation at the levels of the SIIs and of the oscillator neurons. We found: In shortened nerve cord preparations consisting of the head ganglion (supra- and subesophageal ganglia) through segmental ganglia 11 or 12, the effectiveness of swim initiation by Tr1 stimulation was highly correlated with the concurrent injection of depolarizing or hyperpolarizing current into a single cell 204. Tr1 stimulation causes sustained excitation in SIIs, serotonin-containing interneurons and Retzius cells, independent of whether or not swimming is initiated. A short, depolarizing current pulse injected simultaneously into as many as three 204 cells does not replicate the sustained excitation evoked in these cells by Tr1 stimulation. An oscillator neuron, cell 208, is inhibited when Tr1 stimulation fails to elicit swimming, but receives excitatory input from Tr1 otherwise. In another oscillator neuron, cell 115, stimulation of Tr1 suppressed an unidentified source of inhibitory synaptic potentials only on trials which resulted in swim initiation. We conclude that Tr1 stimulation triggers swimming by activating a long-lasting ramp depolarization in the SIIs which, in turn, provide excitatory drive to the swim oscillator. Moreover, Tr1 initiates swimming only when inhibitory inputs to the swim oscillator are suppressed.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of dopamine antagonists on receptive fields of brisk cells and directionally selective cells in the rabbit retina

The effects of dopamine antagonists on the extracellularly recorded activity of ON- and OFF-center brisk ganglion cells and ON-OFF directionally selective ganglion cells in the rabbit retina were investigated. Haloperidol, fluphenazine, and cis-flupenthixol, infused in the arterial system supplying the eye, produced similar effects. In general, these drugs reduced the antagonistic surround responses of brisk ganglion cells, reduced the sustained excitation of the center response of ON-center brisk-sustained cells, reduced the leading edge response of ON-OFF directionally selective cells to moving light stimuli along with any sustained excitation to stationary light stimuli, and affected the spontaneous activity of the cells. These drug effects appear to be due to a blockade of D-1 (adenylate cyclase-linked) receptors and not to D-2 receptors. Neither S-sulpiride nor metoclopramide, two specific D-2 antagonists, had much effect. The findings are the first to describe the functional effects of dopamine antagonists on single cells in the mammalian retina and on ganglion cell activity in the vertebrate retina.

Noise-induced hearing loss can alter neural coding and increase excitability in the central nervous system.

Responses of auditory neurons in the inferior colliculi of mice were studied longitudinally before and shortly after each animal was exposed to intense noise. Noise exposure caused expected losses in auditory sensitivity, but in 31 percent of the neurons studied, unexpected alterations of temporal patterns of action potentials were observed: certain suprathreshold stimuli that had evoked only transient "onset" responses or inhibition of spontaneous discharges prior to noise exposure came to elicit sustained excitation after exposure. Thus, noise-induced hearing loss can be associated with increases in neural responsivity and alterations of normal neural coding processes.

Two methods of operation of a CO2transversely excited waveguide laser

The operation of a CO2 transversely excited (TE) waveguide laser using capacitor discharge excitation and pulser sustainer excitation results in specific output energy densities of 85 mJ m-3 Pa-1 and 113 mJ m-3 Pa-1 respectively. The 3.7% efficiency achieved for the laser when operated in the pulser-sustainer mode is the highest reported for a CO2 TE waveguide laser. Assessment of the waveguide losses results in a correct prediction for the polarisation of the laser output. Consideration of the sustainer discharge allows the arcing limit of the discharge and the form of the sustainer current to be determined.

Response properties of neurons in nuclei of the mouse inferior colliculus

1. Extracellular recordings were obtained from 414 single-units in the inferior colliculi (IC) of tranquilized inbred C57BL/6J mice. 2. Spontaneous activity was encountered in 48% of units in the ventrolateral nucleus (ICVL), in 47% of units in the pericentral and external nuclei (ICP-ICX), and in 39% of units in the dorsomedial nucleus (ICDM). 3. PSTH response patterns typical of IC neurons of other species were found in the mouse (Figs. 2 and 3). These included phasic on and or bursts, off-, sustained excitation, “pauser,” “chopper,” and sustained inhibition of spontaneous activity. Despite the mouse's poor low-frequency hearing, phase-locked responses also occurred. Responses with latencies of up to 100–200 ms which were only driven by relatively long-duration tones were also observed. Other units showed off-suppression of spontaneous activity which could last for several seconds following long-duration tones (Fig. 3). 4. Sustained responses (excitatory and inhibitory) were most prominent in ICVL units, phasic responses in ICP-ICX units, and long-latency and off-responses in ICDM units. Habituation and “sluggish” responses were often found in ICP-ICX units, but rarely were seen in ICVL units. 5. Threshold tuning curves for ICVL units were typified by sharpness and low thresholds, whereas tuning curves of ICP-ICX units were often broad, had higher thresholds, and were difficult to obtain (Figs. 6 and 7). Suprathreshold response ranges of ICVL units strongly represented frequencies of 10–25 kHz, the mouse's most sensitive frequency range. Distributions of response ranges for units in other IC nuclei were more evenly distributed and included more low frequencies (Fig. 8).

Temporal studies with flashed gratings: Inferences about human transient and sustained channels

The temporal response properties of the human visual system to low and high spatial frequency gratings was investigated by two contrast detection threshold techniques. With the first technique the contrast threshold for detecting vertical sinusoidal gratings at spatial frequencies of 0.5, 2.8 and 16.0 c/deg was determined at exposure durations ranging from 20 to 400 msec. It was found that the critical duration, at and below which reciprocity between contrast and a nonunity power of duration holds, increased from roughly 60 to 200 msec as spatial frequency increased from 0.5 to 16.0 c/deg. The second technique involved subthreshold summation of two, 10 msec flashed presentations of either a 1.0 or 10.0 c/deg grating. The stimulus onset asynchrony (SOA) separating the onsets of the two pulses varied from 0 to 210 msec. The results revealed that the subthreshold interaction of the two flashes at high spatial frequencies can be characterized by monophasic sustained excitation and inhibition; at low spatial frequencies, however, this interaction can be characterized by a multiphasic oscillation of excitation and inhibition superimposed on a monophasic excitatory-inhibitory interaction. The findings are related to properties of transient and sustained channels assumed to exist in human vision.

Frequency analysis by neuronal populations in the inferior colliculus of the rat

Response pattern changes of 52 single inferior colliculus (IC) neurons measured as a function of frequency and intensity changes of pure-tone-burst stimuli were analyzer in the form of peri-stimulus-time histograms (PSTH). Through pooling of single unit data and by direct measurement (multiunit PSTH), the typical response pattern of IC neuronal populations was described. This response was an initial damped oscillation (excitation-inhibition) following stimulus onset which was followed by the establishment of a new baseline level of cellular activity that terminated at stimulus offset. A multiunit analysis of the tonotopic organization of rat IC revealed a pattern of activity within populations as predicted by Békésy [Sensory Inhibition (Princeton U.P., Princeton, N.J., 1967)] and I.C. Whitfield [The Auditory Pathway (Camelot Press, London, 1967)]. The onset response was widespread, but sustained excitation was restricted to specific loci for specific tonal frequencies. These excitatory loci were bordered by populations which exhibited sustained inhibition and were observed to shift along a dorso-ventral axis with changes in stimulus frequency.

Sustained decreased in coronary blood flow and excitation of cardiac sensory fibers following sympathetic stimulation.

The effect of electrical stimulation of the efferent cardiac sympathetic nerves on activity of afferent cardiac fibers in the sympathetic nerves and coronary hemodynamics of anesthetized dogs has been examined. During partial constriction of the coronary artery, a brief stimulation of the efferent cardiac sympathetic nerves resulted in sustained excitation of the afferent fibers and a sustained decrease in blood flow of the constricted artery which were associated with systolic bulge of the left ventricle and elevation of the ST segment of electrocardiogram. These changes were not produced without constriction. Pretreatment with phentolamine suppressed excitation of the afferent fibers, development of systolic bulge and elevation of the ST segment. Also, the decrease in coronary blood flow induced by stimulation was replaced by an increase after the administration of the agent. Propranolol suppressed excitation of the fibers, systolic bulge and elevation of the ST segment, but could not eliminate the decrease in blood flow. The results indicate that sympathetic stimulation caused a decrease in coronary blood flow through excitation of the alpha-adrenergic receptors while increasing cardiac work load and energy requirements through excitation of the beta-adrenergic receptors, leading to more severe myocardial ischemia and excitation of the afferent fibers.

Auditory cortical neurons in the cat sensitive to the direction of sound source movement

The neural mechanisms involved in the detection of moving sounds were studied by recording single-neuron responses from primary auditory cortical cells in cats, which were paralyzed and under neuroleptanalgesia. A subpopulation of 25 cells was selected on the basis of brief preliminary tests, from among a group of 60 cells, for quantitative analyzes with a moveable sound source. We recorded, in repeated trials, responses to stationary tones presented from different angles around the animal's head and to the movement of the sound source in several directions in different planes and sectors. Per-stimulus-time (PST) histograms from the responses of each trial series were compiled with a computer. In 5 cells the response patterns depended on the place of the sound source but not on the movement of the sound. Eight cells responded selectively with sustained excitation to the movement of the sound source in a specific direction in a certain sector butreacted either with inhibition or with phasic ‘on’ and ‘off’ responses, or both, to stationary tones presented from different directions. These findings indicate that some cells in the primary auditory cortex of the cat perform a special function in the detection of the direction of sound source movement.

Slow ventricular activation in acute myocardial infarction. A source of re-entrant premature ventricular contractions.

The evolution of premature ventricular contractions (PVCs) in acute myocardial infarction was studied by recording bipolar potentials from the left ventricle before and after coronary artery occlusion in dogs. The potentials were recorded from 154 locations in the left ventricular wall as well as at the endocardial and epicardial surfaces. Desynchronization and marked slowing of previously uniform activation was noted and resembled abbreviated, local fibrillation. The dissociation of excitation was either simple, characterized by fragmentation into single delayed spikes, or complex, characterized by numerous spikes. Sustained, desynchronized activity, confined to local myocardial areas, was observed up to 215 msec after the onset of activation. These local areas of sustained excitation functioned as a source of re-entrant activity and were associated with PVCs. Histochemical stains of myocardium indicated a relationship between the inhomogeneous distribution of ischemia (stain) and the desynchronization of the electrical activity.

Influence of adaptation level on response pattern and sensitivity of ganglion cells in the cat's retina.

1. The effect of background illumination on response pattern is correlated with its effect on visual sensitivity by analysing post-stimulus time-histograms obtained from single ganglion cells in the cat's retina at various levels of background illumination between zero and 2 x 10(6) photons (wave-length 523 nm).sec(-1).deg(-2) (via 5.7 mm(2) pupil).2. If background illumination did not exceed a critical value, about 10(3) photons (523 nm).sec(-1).deg(-2) (via 5.7 mm(2) pupil), stimulation of the centre of a receptive field resulted in either sustained excitation (i.e. increase in discharge rate) during ;on' and cessation of the excitation at ;off' (on-centre unit), or sustained inhibition (i.e. decrease in discharge rate) during ;on' and cessation of the inhibition at ;off' (off-centre unit). Within this low adaptational level, a ganglion cell maintained its maximum sensitivity regardless of whether the weak background light was presented or not.3. When background level exceeded the critical value up to 2 x 10(6) photons (523 nm).sec(-1).deg(-2), however, the simple, sustained responses changed into compound responses with two transient components of opposite polarities, either excitation at ;on' and inhibition at ;off' (on-centre unit), or inhibition at ;on' and excitation at ;off' (off-centre unit), and also the sensitivity began to decrease as the background increased, approximately obeying Weber's law.4. It is suggested that a ganglion cell gives simple-sustained response when its gain control mechanism remains inactive at a low background illumination below a critical level, whereas it gives compound-transient response when its gain control mechanism becomes active as background illumination exceeds the critical value.

Effects of neonatal hypothyroidism on the development of brain excitability in the rat.

The development of electroshock seizure threshold (EST) from 10 to 30 days postnatally and the pattern of maximal electroshock seizure (MES) at 25 days postnatally were studied in normal and neonatally adiothyroidectomized female rats. The results show EST in hypothyroid animals to be consistently and significantly lower than in controls, indicating higher brain excitability in thyroidectomized animals. The MES pattern shows significantly shorter flexion and longer extension in hypothyroid rats, suggesting that the capacity to sustain maximal activity is increased in these animals. Prolonged recovery time from maximal seizures and sustained excitation from minimal seizures was also observed in some hypothyroid animals. Our findings demonstrate that neonatal thyroidectomy impairs the maturation of cortical and/or subcortical structures involved in seizure activity and that the nature of the alteration depends upon the relative degree of maturation of the specific brain area affected.

Responses of cells in the superior olivary complex of the cat to electrical stimulation of the auditory nerve

This study has shown that electrical stimulation of the auditory nerve in the cat at a certain rate will not reproduce the same firing patterns in the cells of the superior olivary complex as a tone of the same frequency. This occurred because the electrical stimulus probably produced synchronous firing of all the auditory nerve fibers, and the inhibitory mechanisms of the cochlear nucleus prevented activation of the auditory cells for all stimulus rates greater than 200/sec. On the other hand, a few cells were recorded in the medial superior olive which gave on- and off-responses to a tone and this firing pattern was reproduced with an electrical stimulus. Although electrical stimulation could not cause sustained excitation of cells, inhibition of spontaneous activity occurred for the duration of the stimulus in a number of cases. This was considered to be due to the effect of efferent stimulation of the olivocochlear bundle on spontaneous activity arising from the cochlea. Bipolar electrical stimulation of the cochlea was also carried out and this excited some cells in the superior olivary complex with characteristic frequencies in the middle to high frequency range. It was not possible to be certain, however, whether this was due to electromechanical stimulation or direct excitation of auditory nerve endings.

Cell volume as a factor influencing electrical and mechanical activity of vascular smooth muscle.

ABSTRACTThe effects of variations in the extracellular osmolarity on the electrical and mechanical activity of the isolated rat portal vein were studied. Addition of sucrose or xylose (20–100 mmoles/l) to the “normal” solution caused inhibition of contractile activity which could be ascribed to changes in the electrical discharge pattern. Increasing osmolarity with urea produced transient inhibition, return to control activity, and, on return to normal solution, a transient excitation. Reducing osmolarity by 30–60 mOsm/l by decreasing the [Na+] and [Cl] of the medium caused sustained excitation with continuous spike discharge and tetanic contraction. Comparable decreases in the ionic concentrations but with osmotic substitution by sucrose or xylose had little influence on muscle activity. Substituting Na+ and Cl with urea on an equiosmolar basis caused excitation resembling that in hypoosmotic solution. If the smooth muscle cells are looked upon as osmotic cells with membranes that are freely permeable to H2O and urea but less permeable to sugar and ions, the results indicate a consistent correlation between cell volume and state of activity; shrinkage associated with inhibition, swelling with excitation. Changes in the transuiembrane concentration gradients for K+, Na+ and Cl‐, caused by the cellular volume changes, are not sufficient to explain the electrical responses. Changes in ionic membrane permeability are assumed to occur.

Cell Volume as a Factor Influencing Electrical and Mechanical Activity of Vascular Smooth Muscle

The effects of variations in the extracellular osmolarity on the electrical and mechanical activity of the isolated rat portal vein were studied. Addition of sucrose or xylose (20–100 mmoles/l) to the “normal” solution caused inhibition of contractile activity which could be ascribed to changes in the electrical discharge pattern. Increasing osmolarity with urea produced transient inhibition, return to control activity, and, on return to normal solution, a transient excitation. Reducing osmolarity by 30–60 mOsm/l by decreasing the [Na+] and [Cl] of the medium caused sustained excitation with continuous spike discharge and tetanic contraction. Comparable decreases in the ionic concentrations but with osmotic substitution by sucrose or xylose had little influence on muscle activity. Substituting Na+ and Cl with urea on an equiosmolar basis caused excitation resembling that in hypoosmotic solution. If the smooth muscle cells are looked upon as osmotic cells with membranes that are freely permeable to H2O and urea but less permeable to sugar and ions, the results indicate a consistent correlation between cell volume and state of activity; shrinkage associated with inhibition, swelling with excitation. Changes in the transuiembrane concentration gradients for K+, Na+ and Cl-, caused by the cellular volume changes, are not sufficient to explain the electrical responses. Changes in ionic membrane permeability are assumed to occur.

Concerning the Interrelation between Absolute Sensitivity and Strength of the Nervous System

Summary This paper is concerned with the relation between absolute sensitivity and the “strength” of the C.N.S., in the sense in which the term was used By Pavlov. The authors advance the hypothesis that “weakness” of the nervous system is correlated with high reactivity, and hence with high sensitivity to peripheral stimulation; conversely, “strength” of the nervous system is correlated with low reactivity; and hence with low sensitivity to peripheral stimulation. Two sets of experiments were carried out in order to test this hypothesis, one concerned with visual and the other with auditory sensitivity. In the visual experiments, absolute sensitivity to light in the periphery of the dark adapted eye was measured on 26 subjects by means of an adaptometer. Measurements were taken at two minute intervals over a period of about half an hour, the mean threshold value for each subject being calculated from the results obtained at a number of experimental sessions distributed over 3 to 5 days. In the auditory experiments, absolute threshold for sound intensity was determined in 22 subjects. A pure tone of 1,000 c.p.s. was fed to the subject binaurally through headphones and the sound pressure level systematically varied by the experimenter. Threshold measurements were made at 1 min. intervals over a 15 to 20 min. period. Sensitivity is calculated as a value inversely proportional to that of the threshold. In order to determine the “strength” of nerve cells, the authors made use of a method involving a conditioned decrease of sensitivity to light or sound. The rationale of the method is as follows: The strength of a conditioned reflex is normally found to increase with increase in intensity (or duration) of the conditioned stimulus until a “physiological limit” is reached. Above this limit, further increase in stimulus intensity no longer produces an increase in response, which may indeed diminish as a consequence of “trans-marginal inhibition”. Hence a determination of the stimulus intensity above which there is no increase in response strength provides a method of defining the physiological limit, or “strength”, of the central nervous processes involved. The actual method used here consisted in exposure for 10 to 15 sec. of an illuminated panel as the unconditioned stimulus, the resulting reduction in peripheral visual sensitivity being the unconditioned response. A pure tone of 1,000 c.p.s. and a red light of low intensity were used as conditioned stimuli. The conditioned stimulus was applied 5 sec. before the onset of the unconditioned stimulus, the duration of their combined application being 10 sec. After the conditioned reflex was well established the tests of “strength” were begun. These consisted in the application of the conditioned stimulus (always reinforced) ten times in succession at intervals of 2 min. The conditioned stimulus was also presented twice without reinforcement, once at the beginning and again at the end of the series. If the strength of the conditioned reflex showed no decrement on this second trial as compared with the first, it was concluded that the physiological limit or “strength” of the corresponding central nervous structures was high; if, however, there was decrement, this was taken to mean a low physiological limit or “weakness”. The criterion of decrement was a decrease in strength of the conditioned reflex of 10 per cent. or more. These experiments were also repeated after the administration of 0.2 gr. of caffeine, which is thought to raise the excitability, and hence diminish the “strength”, of central nervous processes. The results appear to demonstrate a negative correlation between sensitivity, visual or auditory, and the “strength” of nervous processes. In general, subjects with “weak” nervous systems gave low absolute threshold values, indicating high sensitivity, whereas those with “strong” nervous systems gave high threshold values, indicating low sensitivity, There were, however, some exceptions to this rule. In discussion of these results, the authors lay stress on functional changes which are believed to occur in neurones as a consequence of sustained excitation. In general, they argue that both sensitivity and “strength” of nervous processes can be related to a more basic dimension of neural “reactivity”.