Electrophysiological and pharmacological analysis of L-dopa-induced dyskinesia and tardive dyskinesia (author's transl)

Electrophysiological and pharmacological analysis of L-Dopa-induced dyskinesia and tardive dyskinesia (L.DD) due to neuroleptics was performed on 12 patients with Parkinson's disease and on 12 others with psychotic diseases. This analysis included the examination of spinal reflexes, monosynaptic H reflex, polysynaptic cutaneous reflex of the lower limb, muscular responses to passive movement [stretch reflex and shortening reaction (SR)] and the study of the motor response to a dopaminergic stimulus (I.V. injection of Piribedil (PBD), a dopamine agonist). There was no difference in EMG activity between L.DD and TD. Three EMG patterns can be distinguished: anarchic discharge pattern (ADA), tonic grouping discharge pattern (AST) and rhythmic burst pattern (ABR). PBD effects indicate a possible relationship between the EMG patterns and the sensitivity level of the motor dopamine receptors. During L-Dopa dyskinesia and tardive dyskinesia, the same changes in spinal reflexes were observed. Muscle tone tested by muscular responses to passive movement (shortening and myotatic reaction) was normal. Monosynaptic excitability explored by H/M ratio was within the normal range. In contrast, the polysynaptic nociceptive reflex was increased in every case. In Parkinsonian patients with L-Dopa dyskinesia, this pattern of the spinal reflexes was significantly different in comparison to the rigid phase. Intravenous infusion of PBD suppressed tremor and provoked the occurrence of dyskinetic activity in Parkinsonian patients with L-Dopa dyskinesia during the rigid phase. During the dyskinetic phase, as in tardive dyskinesia, PBD increases these phenomena and changes EMG activity in rhythmic pattern. It is suggested that L-Dopa dyskinesia and tardive dyskinesia can be determined by testing EMG activity, spinal reflexes and dopaminergic reactivity. There is evidence to suggest that the various types of involuntary abnormal movement represent a single entity, and that dopamine receptor supersensitivity may be involved.     

Frequency-dependent excitability of "membrane" slow responses of Rabbit left atrial trabeculae in the presence of Ba2+ and high K+

Small trabeculae of rabbit left atrium immersed in TKBa solution (Tyrode with 10 mM K+ and 1 mM Ba2+) were used to study frequency dependence of "membrane" slow response excitability at long cycle lengths (greater than 1 s). In TKBa, stimuli generate graded, low- amplitude (2-15 mV) subliminal responses of variable long duration (up to 450 ms). A full all-or-none slow response is generated when a subliminal response depolarizes the membrane to about--35 mV. Subliminal response amplitude and rate of rise augment with stimulus intensity-duration product. For a fixed stimulus, the subliminal response is larger and faster at higher frequencies. Sudden changes in stimulus frequency or time course induce changes in subliminal response tha take four to eight cycles to attain steady state. For a fixed stimulus, slow response latency shortens progressively during the first few cycles after a sudden increase in frequency or when a rested preparation is excited (latency adaptation phenomenon, LAP). Slow response threshold stimulus requirements decrease during LAP (excitability hysteresis). The degree of excitability hysteresis is dependent on stimulation frequency and is more pronounced at higher frequencies. Frequency sensitivity of subliminal response (which causes frequency sensitivity of slow response excitability) is explained in terms of a transient state of enhancement set up by each stimulus. The enhanced state decays between stimuli with a half-time of approximately 4 s, thus allowing cumulative effects to become evident at rates above 0.1 Hz.     

Proprioceptive proximo-distal relationships between the quadriceps and soleus muscles in man

Electrical stimulation of femoral nerve modulates voluntary tonic activity o of ipsilateral soleus muscle. Stimulus time-locked inhibitory and facilitatory phases can be distinguished. EMG temporal analysis suggests that early perturbations are correlated with spinal effects of centripetal electrical activity. The inhibitory effects which momentarily abolish voluntary soleus activity are thought to result from quadriceps Ib fibres recruitment. While no heteronymous activity is induced at rest, femoral nerve Ia fibres activation can produce soleus muscle reflex when soleus motor nucleus excitability is increased by voluntary command. Recurrent discharge resulting from soleus reflex response enhances inhibition initially due to quadriceps Ib volley. Secondary effects of isometric quadriceps contraction (and soleus contraction when the femoral stimulus elicits a reflex in this muscle) have their own effects later. These findings suggest that proprioceptive relationships of the two muscular groups are efficient during tonic isometric voluntary command.     

The investigation of locomotor activity control system in humans under the air-stepping conditions during passive and voluntary leg movements

The degree of activation of the central stepping program during passive leg movement was studied in healthy subjects under unloading conditions; the excitability of spinal motoneurons was studied during passive and voluntary stepping movements. Passive stepping movements with characteristics maximally close to those during voluntary stepping were accomplished by the experimenter. The bursts of muscular activity during voluntary and imposed stepping movements were compared. In addition, the influence on the leg movement of artificially created loading onto the foot was studied. The excitability of spinal motoneurons was estimated by the amplitude of modulation of the m. soleus H reflex. Changes in the H reflex (Hoffmann’s reflex) after fixation of the knee and hip joints were also studied. In most subjects, passive movements were accompanied by bursts of electromyographic (EMG) activity in the hip muscles (sometimes in shank muscles); the timing of the EMG burst during the step cycle coincided with the burst’s timing during voluntary stepping. In many cases, the bursts in EMG activity exceeded the activity of homonymous muscles during voluntary stepping. Simulation of foot loading influenced significantly the distal part of the moving extremity during both voluntary and passive movements, which was expressed in the appearance of movements in the ankle joint and an increase in the phasic EMG activity of the shank muscles. The excitability of motoneurons during passive movements was higher than during voluntary movements. Changes and modulation of the H reflex throughout the step cycle were similar without restriction of joint mobility and without hip joint mobility. Fixation of the knee joint was of great importance. It is supposed that imposed movements activate the same mechanisms of rhythm generation as supraspinal commands during voluntary movements. During passive movements, presynaptic inhibition depends mostly on the afferent influences from the moving leg rather than on the central commands. Under the conditions of “air-stepping,” the afferent influences from the foot pressure receptors are likely to interact actively with the central program of stepping and to determine the final activity pattern irrespective of the movement type (voluntary or passive).     

Effects of hypoxia on genioglossus and scalene reflex responses to brief pulses of negative upper-airway pressure during wakefulness and sleep in healthy men.

Hypoxia can depress ventilation, respiratory load sensation, and the cough reflex, and potentially other protective respiratory reflexes such as respiratory muscle responses to increased respiratory load. In sleep-disordered breathing, increased respiratory load and hypoxia frequently coexist. This study aimed to examine the effects of hypoxia on the reflex responses of 1) the genioglossus (the largest upper airway dilator muscle) and 2) the scalene muscle (an obligatory inspiratory muscle) to negative-pressure pulse stimuli during wakefulness and sleep. We hypothesized that hypoxia would impair these reflex responses. Fourteen healthy men, 19-42 yr old, were studied on two separate occasions, approximately 1 wk apart. Bipolar fine-wire electrodes were inserted orally into the genioglossus muscle, and surface electrodes were placed overlying the left scalene muscle to record EMG activity. In random order, participants were exposed to mild overnight hypoxia (arterial oxygen saturation approximately 85%) or medical air. Respiratory muscle reflex responses were elicited via negative-pressure pulse stimuli (approximately -10 cmH(2)O at the mask, 250-ms duration) delivered in early inspiration during wakefulness and sleep. Negative-pressure pulse stimuli resulted in a short-latency activation followed by a suppression of the genioglossus EMG that did not alter with hypoxia. Conversely, the predominant response of the scalene EMG to negative-pressure pulse stimuli was suppression followed by activation with more pronounced suppression during hypoxia compared with normoxia (mean +/- SE suppression duration 64 +/- 6 vs. 38 +/- 6 ms, P = 0.006). These results indicate differential sensitivity to the depressive effects of hypoxia in the reflex responsiveness to sudden respiratory loads to breathing between these two respiratory muscles.     

Direct cortical responses to electric stimulation with different frequencies in chronic experiments on dogs]

Direct cortical responses (DCR) to a series of electrical stimuli with a frequency of I to 50 per second with 10 to 20 pulses in each series were studied in chronic experiments on dogs. The nature of cortical responses differed, depending on stimulation parameters. As the stimulation frequency increased, the amplitude and number of late DCR components decreased, and with further increase of frequency, the early components decreased as well. The following types of responses were revealed: recruiting, intermittent and decremental. As the stimulation frequency increased all the three types of responses could be obtained in one and the same cortical point. Recruiting was not typical of high-amplitude and multi-component DCR with a long phase of depression of initial negativity and slightly pronounced short-term subsequent facilitation, while the intermittent type of response appeared at lower frequencies than in other dogs (5 to 10 per sec). A decremental type of response was observed in all the dogs at a stimulation frequency higher than 30 per sec. The duration of the series of after-discharges to a burst of electrical pulses depended on the pattern of the DCR to a single stimulus and on the intensity and frequency of stimulation. With similar parameters of stimulation, the greater the amplitude and the longer the duration of the slow negative DCR wave, the longer the period of after-discharges following a series of stimuli.     

Intensity Characteristics of the Noctuid Acoustic Receptor

Spiking activity of the more sensitive acoustic receptor is described as a function of stimulus intensity. The form of the intensity characteristic depends strongly on stimulus duration. For very brief stimuli, the integral of stimulus power over stimulus duration determines the effectiveness. No response saturation is observed. With longer stimuli (50 msec), a steady firing rate is elicited. The response extends from the spontaneous rate of 20–40 spikes/sec to a saturated firing rate of nearly 700 spikes/sec. The characteristic is monotonic over more than 50 db in stimulus intensity. With very long stimuli (10 sec), the characteristics are nonmonotonic. Firing rates late in the stimulus decrease in response to an increase in stimulus intensity. The non-monotonic characteristics are attributed to intensity-related changes in response adaptation.     

Inhibition of spinal reflex responses in the last period of embryogenesis

Some characteristics of spinal reflex reaction inhibition were studied in cat fetuses during the last three weeks of antenatal development. The experiments were conducted on fetuses with intact placental circulation. Restoration of the excitability of the spinal reflex arcs was very slow after stimulation of the dorsal root by a single stimulus. In embryos studied 20 days before birth the full inhibition of reflex responses lasted about 500 msec. Even 2–3 sec after a single stimulation of the afferent fibers the amplitude of the reflex response to the second stimulus was only 30–40% of the control value. It was determined that such long postactivation depression is unrelated to refractoriness or antidromic inhibition. The presence of a prolonged intense depolarization of afferent terminal fibers at these stages suggests a presynaptic inhibition as one of the most probable reasons for the prolonged postactivation depression. Another important factor in the appearance of postactivation depression is probably the morphologic and functional immaturity of synaptic structures. A reciprocal inhibition was observed in cat fetuses on the 10–12th antenatal day. On the basis of these data it is suggested that in embryogenesis presynaptic inhibition considerably precedes that of postsynaptic fibers.Institute of Higher Nervous Activity and Neurophysiology, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 3, No. 1, pp. 68–75, January–February, 1971.     

Responses of simple and non-oriented cells to stimuli of variable duration in areas 17 and 18 of cat visual cortex.

Single unitresponses to photic stimuli of variable duration were studied in the cat visual areas 17 and 18. The closed-chamber technique was used to record extracellularly impulsive electrical activity in locally anaesthetized, Flaxedil-paralyzed and artificially ventilated cats. Stimulus duration ranges between 0.020 and 10 sec, the background luminance and the intensity of stimuli being constant. We found a first group of cells which fire independently of the stimulus duration; a second group which fire in close relation to the stimulus duration in a rather wide range of values, and a third group which fire monotonously as long as the stimulus goes on. The three groups of cells are supposed to be three functionally different types of cortical cells.     

Modulation of the visceromotor reflex by a lumbosacral ventral root avulsion injury and repair in rats

Increased abdominal muscle wall activity may be part of a visceromotor reflex (VMR) response to noxious stimulation of the bladder. However, information is sparse regarding the effects of cauda equina injuries on the VMR in experimental models. We studied the effects of a unilateral L6-S1 ventral root avulsion (VRA) injury and acute ventral root reimplantation (VRI) into the spinal cord on micturition reflexes and electromyographic activity of the abdominal wall in rats. Cystometrogram (CMG) and electromyography (EMG) of the abdominal external oblique muscle (EOM) were performed. All rats demonstrated EMG activity of the EOM associated with reflex bladder contractions. At 1 wk after VRA and VRI, the duration of the EOM EMG activity associated with reflex voiding was significantly prolonged compared with age-matched sham rats. However, at 3 wk postoperatively, the duration of the EOM responses remained increased in the VRA series but had normalized in the VRI group. The EOM EMG duration was normalized for both VRA and VRI groups at 8-12 wk postoperatively. CMG recordings show increased contraction duration at 1 and 3 wk postoperatively for the VRA series, whereas the contraction duration was only increased at 1 wk postoperatively for the VRI series. Our studies suggest that a unilateral lumbosacral VRA injury results in a prolonged VMR to bladder filling using a physiological saline solution. An acute root replantation decreased the VMR induced by VRA injury and provides earlier sensory recovery.     

Repetitive calcium stimuli drive meiotic resumption and pronuclear development during mouse oocyte activation.

Freshly ovulated (12 hr post hCG) F1 (C57BL/6 x CBA) hybrid mouse oocytes were parthenogenetically activated by repetitive elevation of Ca2+ induced by carefully controlled electrical pulses. Different patterns of stimulation were employed to examine the role of repetitive calcium changes on meiotic resumption and pronuclear development. In the first series of experiments oocytes received 33 electrical pulses of 1.8 kV/cm delivered every 4 min. The pulse duration decreased according to a negative exponential equation from a 900-microseconds first pulse to give a total pulse duration of 18.721 msec. The strength of calcium stimuli was varied by changing the concentration of CaCl2 in the medium. Ninety-eight percent of the oocytes stimulated with 12 microM calcium extruded the second polar body by the end of treatment and 92% completed pronuclear formation between 3.5 and 8 hr after the first pulse. For higher or lower Ca2+ concentrations the proportion of oocytes developing pronuclei decreased; the timing of pronuclear formation was retarded and the majority of oocytes failed to form a pronucleus after extrusion of the second polar body. In the second series of experiments, the strength of the calcium stimuli was modulated by changing the duration of the 33 electrical pulses given in the presence of 12 microM calcium. By increasing the total pulse duration to 33.958 msec, 100% of the oocytes activated and completed pronuclear formation between 3 and 5 hr after the first electric pulse. Stimulation protocols of lower total pulse duration (less than 18.721 msec) gave rise to high rates of partial activation (up to 95%). Examination of these partially activated oocytes showed metaphases with haploid sets of chromatids characteristic of third meiotic metaphase arrest. The results indicate that repetitive calcium stimuli can regulate the rate and extent of meiotic resumption and the time course of pronuclear formation during mouse oocyte activation. They suggest that meiotic resumption in mammalian oocytes is regulated by the amplitude and frequency of cytosolic calcium oscillations induced by the activating stimulus.     

Excitability cycles of direct cortical responses during elaboration of conditioned defense reflexes in dogs]

Direct cortical responses (DCRs) to paired stimuli were studied in chronic experiments in dogs during elaboration of classical and instrumental defensive conditioned reflexes. The DCRs were recorded with 20 to 250 ms intervals between stimuli. Paired and single electrical stimulations of the middle suprasylvian gyrus given with a frequency of one per second were used as conditioned stimuli and were reinforced in a similar way. During electrical cutaneous stimulation of the dog's paw and to an even greater extent during isolated action of the conditioned stimulus the initial negativity of the testing DCR became shorter and the degree of its depression diminished. In the case of a following period of facilitation, its degree became greater. It was higher at a distance of 4 to 5 mm from the point of stimulation than at a distance of 2 to 3 mm. During isolated action of the conditioned stimulus, the degree of facilitation was higher than at the period of the possible action of the unconditioned stimulus. The greatest shorterning of the DCR excitability cycle was observed immediately before and during the conditioned lifting of the dog's paw. Excitability cycles of DCR, and possibly of other evoked potentials as well, are a more sensitive indicator of the function state of the cerebral cortex than responses to single stimuli. For this reason it appears promising to use them in studying conditioned reflexes.     

Responses of motor cortex neurons of the cat to auditory stimulation and their role in the instrumental food reflex

The responses of motor cortex neurons in the cat to the presentation of a single auditory click and a series of 10 clicks presented with 1,000/sec frequency were studied under conditions of chronic experiments before and after the development of an instrumental food reflex. After reflex development a single presentation of a positive conditioned stimulus (single click) markedly influenced for 7 sec the appearance of instrumental movements. At the same time, the immediate responses of motor cortex neurons to presentation of the conditioned auditory stimulus had no impact on the appearance in the motor cortex of discharges leading to the realization of instrumental movements. Consequently, motor cortex neurons do not require activation from afferent sensory inputs for the generation of such discharges. The immediate neuronal responses to conditioned stimulation did not inhibit the realization of the instrumental reflex. It is proposed that they are associated with the realization of motor function in the unconditioned defensive response evoked by the presentation of an auditory stimulus. The presence or absence of responses to auditory conditioned stimulation was dependent upon the signal meaning of the stimulus, its physical parameters, and the degree of excitability of the animal.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 17, No. 4, pp. 539–550, July–August, 1985.     

Supraspinal influences on the penile reflexes of the male rat: a comparison of the effects of copulation, spinal transection, and cortical spreading depression.

The penile reflexes of the rat were observed on interruption of the copulatory behavior sequence after intromission and ejaculation in the initial ejaculatory series, after the penultimate series, during sexual exhaustion, and during recovery from sexual exhaustion 24 and 72 hr later. These were compared to the reflexes of the normal rat in control conditions, to those of the male rat after spinal transection, and to those of the sexually rested and sexually exhausted male rat under cortical spreading depression (CSD). It was concluded that (1) the stimuli associated with copulation evoke disinhibition of the penile reflexes, these showing the short reflex latencies observed in the spinal animal. The release of the spinal mechanisms is lost within 30 min of the last copulatory event. CSD further inhibits reflex responsivity. (2) Stimuli associated with intromission provoke acceleration of the normal rhythmic presentation of reflexes seen in the normal and spinal rat, resulting in a decrease in the duration of intervals between reflex clusters and an increase in reflex number. This excitation decays within about 15 min after intromission. (3) The increase in degree of penile extension and percentage of penile flips after spinal transection suggests tonic inhibition of reflex intensity in the normal rat. The decrease in capacity to attain full erection with the approach of sexual exhaustion suggests an increase in this inhibition. This does not recover during a rest period but instead intensifies. CSD effects did not mimic the effects of spinal transection but instead depressed reflex excitability. The relationship of these changes to the copulatory behavior pattern is discussed.     

Frequency response characteristics of electroreceptors in weakly electric fish (Gymnotoidei) with a pulse discharge

Summary Three species of Gymnotid fish, two species ofHypopomus andRhamphichthys rostratus, each having pulse type electric organ discharges (EOD) of different durations were studied to learn if any correlation exists between the spectral composition of the species specific EOD pulse and the frequency response characteristics of that species' electroreceptors. The receptor population consisted of two major categories (examples in Fig. 3). One category, termed pulse marker receptors, responded to suprathreshold stimulus pulses with a single spike at a short (<2 ms) latency. These receptors were tuned to the higher frequency components of a species' EOD (Fig. 4A) and were always 5 to 10 dB less sensitive than any other electroreceptors within a given species. The second major receptor category, burst duration coders, responded to an electrical stimulus with a burst of spikes at a longer latency, burst length was a function of stimulus amplitude. This second category could be further divided into three sub-categories according to the receptors' frequency response characteristics. The most commonly seen subcategory, wide band receptors (Fig. 4B), responded best to stimuli having frequencies equal to the dominant frequency component of the species' EOD in the two species ofHypopomus studied. A second subcategory, narrow band receptors (Fig. 4 A), had frequency response characteristics similar to those of the pulse marker receptors; however, these had thresholds 10 dB lower than those of the pulse marker. The third subcategory of burst duration coders, low frequency receptors (Fig. 4 C, D), responded best to stimulus frequencies ranging from about 50 to 150 Hz. Mechanisms of coding stimulus amplitude and responses to prolonged sinusoidal electrical stimuli were also studied in the various receptor types.It is suggested that the differences in the major receptor types and the different frequency response characteristics of the electroreceptors within a given species allows the animals to identify and evaluate signals resulting from their own EOD, the EODs of conspecifics and electrical stimuli generated by other species of electric fish.Supported by NIH Grant #1 RO1 NS 12337-01     

Optimal stimulation settings for CMAP scan registrations

Background

The CMAP (Compound Muscle Action Potential) scan is a non-invasive electrodiagnostic tool, which provides a quick and visual assessment of motor unit potentials as electrophysiological components that together constitute the CMAP. The CMAP scan records the electrical activity of the muscle (CMAP) in response to transcutaneous stimulation of the motor nerve with gradual changes in stimulus intensity. Large MUs, including those that result from collateral reinnervation, appear in the CMAP scan as so-called steps, i.e., clearly visible jumps in CMAP amplitude. The CMAP scan also provides information on nerve excitability. This study aims to evaluate the influence of the stimulation protocol used on the CMAP scan and its quantification.

Methods

The stimulus frequency (1, 2 and 3 Hz), duration (0.05, 0.1 and 0.3 ms), or number (300, 500 and 1000 stimuli) in CMAP scans of 23 subjects was systematically varied while the other two parameters were kept constant. Pain was measured by means of a visual analogue scale (VAS). Non-parametric paired tests were used to assess significant differences in excitability and step variables and VAS scores between the different stimulus parameter settings.

Results

We found no effect of stimulus frequency on CMAP scan variables or VAS scores. Stimulus duration affected excitability variables significantly, with higher stimulus intensity values for shorter stimulus durations. Step variables showed a clear trend towards increasing values with decreasing stimulus number.

Conclusions

A protocol delivering 500 stimuli at a frequency of 2 Hz with a 0.1 ms pulse duration optimized CMAP scan quantification with a minimum of subject discomfort, artefact and duration of the recording. CMAP scan variables were influenced by stimulus duration and number; hence, these need to be standardized in future studies.     

Self-Sustained Motor Activity Triggered by Interlimb Reflexes in Chronic Spinal Cord Injury,Evidence of Functional Ascending Propriospinal Pathways

The loss or reduction of supraspinal inputs after spinal cord injury provides a unique opportunity to examine the plasticity of neural pathways within the spinal cord. In a series of nine experiments on a patient, quadriplegic due to spinal cord injury, we investigated interlimb reflexes and self-sustained activity in completely paralyzed and paretic muscles due to a disinhibited propriospinal pathway. Electrical stimuli were delivered over the left common peroneal nerve at the fibular head as single stimuli or in trains at 2–100 Hz lasting 1 s. Single stimuli produced a robust interlimb reflex twitch in the contralateral thumb at a mean latency 69 ms, but no activity in other muscles. With stimulus trains the thumb twitch occurred at variable subharmonics of the stimulus rate, and strong self-sustained activity developed in the contralateral wrist extensors, outlasting both the stimuli and the thumb reflex by up to 20 s. Similar behavior was recorded in the ipsilateral wrist extensors and quadriceps femoris of both legs, but not in the contralateral thenar or peroneal muscles. The patient could not terminate the self-sustained activity voluntarily, but it was abolished on the left by attempted contractions of the paralyzed thumb muscles of the right hand. These responses depend on the functional integrity of an ascending propriospinal pathway, and highlight the plasticity of spinal circuitry following spinal cord injury. They emphasize the potential for pathways below the level of injury to generate movement, and the role of self-sustained reflex activity in the sequelae of spinal cord injury.     

Fusimotor reflex profiles of individual triceps surae primary muscle spindle afferents assessed with multi-afferent recording technique.

The experiments were performed on 21 cats anaesthetized with alpha-chloralose. The aim of the study was to investigate sets of simultaneously recorded spindle afferents (2-4 in each set) from the triceps surae muscle (GS) with respect to the pattern of fusimotor reflex effects evoked by different types of ipsi- and contralateral reflex stimulation. The afferents' responses to sinusoidal stretching of the GS muscle were determined and the fusimotor reflex effects were assessed by comparing the afferent responses (i.e. the mean rate of firing and the depth of modulation) elicited during reflex stimulation with those evoked in absence of any reflex stimulus. Natural of electrical activations of ipsi- and contralateral muscle, skin and joint receptor afferents were used as reflex stimuli. The spindle afferents were influenced by several modalities and from wide areas, with a majority responding to both ipsi- and contralateral stimuli. A particular reflex stimulus often caused different effects on different afferents, and the various reflex stimuli seldom gave similar effects on a particular afferent. Multivariate analysis revealed that the variation in response profiles among simultaneously recorded afferents were as great as between afferents recorded on different occasions. This suggests that the individualized response prifiles, observed in earlier investigations, represent a very diversified reflex control of the spindle primary afferents, and are not a reflection of changes in the setting of the spinal interneuronal network, occurring during the time interval between the recordings of different units. Also, there was no relation between the conduction velocity of the afferents and the reflex profiles of the afferents, but non-linear relations were found between effects elicited by different types of stimuli. Indications were also found that it may be possible to separate the population of GS muscle spindles into subgroups, according to the fusimotor effects exhibited by activation of various categories of ipsi- and contralateral receptor afferents. It is concluded that one possible way of making the very complex reflex system controlling the muscle spindles intelligible may be a combination of multiple simultaneous recordings of spindle afferents and multivariate analysis.     

Direct cortical response in the cat motor cortex during summation

Summation was studied by a procedure close to that used in producing a conditioned reflex. Subthreshold electrical stimulation, which gave rise to a dominant focus in the cat motor cortex, was applied after photic stimulation. Under these conditions, summation occurred both when the two stimuli were applied simultaneously and when the weaker stimulus preceded the stronger one by a very short interval (tens of milliseconds). Increased excitability was characteristic of the dominant focus. An excessive increase in excitability weakened the summation reflex. Electrographically, this type of conditioning was reflected in an increase in amplitude of the primary negative wave of the direct cortical response, recorded in the motor area at a distance of 2–3 mm from the stimulation point. It is concluded from analysis of this electrophysiological phenomenon and comparison of the results with data in the literature that different mechanisms are involved in the summation process during different sequences of stimulation ("photic+electrical" and "electrical+photic").Institute of Higher Nervous Activity and Neurophysiology, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 1, No. 3, pp. 293–302, November–December, 1969.     

Local circuitry in the IMHV of the domestic chick (Gallus domesticus)

The responses to local stimulation have been recorded from neurons in the intermediate part of the medial hyperstriatum ventrale (IMHV) of the domestic chick, by using an in vitro slice preparation. When the slice is bathed in gassed Krebs' solution, a single stimulus evokes a short-lasting diphasic response. The first phase is negative and lasts some 3 ms, whereas the second, positive phase is often of lower amplitude and usually persists for about 15 ms. The first phase is little altered by perfusion with either Ca2(+)-free Krebs' solution or Krebs' solution containing a high concentration of Mg2+. In contrast, the second phase is abolished by these procedures. The post-synaptic phase is positive when it is recorded anywhere between 0.1-1.25 mm from the stimulated point; however, in the immediate vicinity (0.0-0.1 mm) of the stimulating electrodes, the post-synaptic response is strongly negative. A pair of stimuli has to be separated by at least 10 s to guarantee complete recovery of excitability of the post-synaptic response. The recovery curve for this response shows a refractory period of some 5 ms, a peak of excitability at an interval of about 20 ms, and then a sharp trough of relative inexcitability at about 200 ms. The post-synaptic response is considerably reduced in magnitude and duration by the addition of AP-5 to the perfusion fluid; the remaining post-synaptic response is completely abolished by kynurenic acid. The addition of bicuculline methiodide in concentrations of at least 1 x 10(-6) M increases both the magnitude and duration of the second, positive phase of the response to single stimuli. This extended positive response (which may last from 500-800 ms) is abolished by perfusion with bicuculline dissolved in Ca2(+)-free Krebs' solution. For the entire duration of the extended post-synaptic positive response produced by bicuculline, the irregular discharge of single neurons can be recorded. Like the post-synaptic positive response in Krebs' solution, the much larger response produced by bicuculline shows a very localized negativity beneath the stimulating electrodes and displays an almost identical time-course for the recovery of excitability following a single stimulus. The bicuculline induced positive response is also considerably reduced by the presence of AP-5; the addition of kynurenic acid abolishes the remaining post-synaptic response completely. A post-synaptic response, similar to that produced under bicuculline, can be produced by the addition of a maximally effective dose of d-tubocurarine.(ABSTRACT TRUNCATED AT 400 WORDS)