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Short-term synaptic plasticity contributes to the temporal filtering of electrosensory information.

Short-term synaptic depression and facilitation often are elicited by different temporal patterns of activity. Short-term plasticity may contribute, therefore, to temporal filtering by impeding synaptic transmission for some temporal patterns of activity and facilitating transmission for other patterns. We examined this hypothesis by investigating whether short-term plasticity contributes to the temporal filtering properties of midbrain electrosensory neurons. Postsynaptic potentials were recorded in response to sensory stimuli and to direct stimulation of afferents, in vivo. Stimulating afferents with pairs of pulses at a rate of 20 pairs/sec ["tetanus (20 Hz)"] induced PSP depression. This PSP depression was similar to that observed for electrosensory stimuli of the same temporal frequency. Analysis of PSPs elicited by a pair of pulses that preceded versus followed the tetanus revealed that PSP depression was caused by synaptic depression, not by a loss of facilitation. Behavioral studies indicate that fish can detect slow changes in signal amplitude (slow AM) in backgrounds of fast fluctuations. Correspondingly, midbrain neurons respond well to slow AM even in the presence of fast AM. In many neurons, facilitation enhanced responses to trains (8-10 pulses; 100 Hz) that represented activity patterns elicited by slow AM, despite induction of synaptic depression by a tetanus (20 Hz). The interplay between synaptic depression and facilitation, therefore, can act as a filter of temporal information. Some neurons that showed little facilitation nonetheless responded to low temporal-frequency information after induction of depression by fast information; this likely results from the convergence of inputs with different temporal filtering properties.

Animals↗

Effects of heterotopic noxious stimuli on activity of neurones in subnucleus reticularis dorsalis in the rat medulla.

1. In anaesthetized rats, recordings were made in the medullary subnucleus reticularis dorsalis. Neurones with total nociceptive convergence (TNC) responded to percutaneous electrical stimuli with early and late peaks due to the activation of A delta and C fibres respectively, no matter which part of the body was stimulated. Neurones with partial nociceptive convergence (PNC) responded with an A delta peak regardless of which part of the body was stimulated, and with a C peak of activation from some, mainly contralateral, parts of the body. 2. All TNC neurones responded to noxious thermal stimulation of the limbs with a phasic discharge followed by tonic activity that lasted throughout the stimulation. Discharges elicited by applying stimuli simultaneously to both forepaws or to a hindpaw and a forepaw were lower than the individual responses to stimulation of a single limb. Similar negative interactions were observed in the responses of PNC neurones following noxious thermal stimulation of two paws. 3. In both neuronal populations, the simultaneous application of noxious thermal stimuli and microelectrophoretic application of D,L-homocysteic acid (DLH) induced responses of greater magnitude than those evoked by each stimulus alone. 4. TNC neurones responded to electrical stimulation of the contralateral hindpaw with A delta and C fibre responses. Noxious thermal stimuli applied to different areas of the body induced an excitatory response during the period that preceded the electrical stimulation, but an inhibition of both A delta and C fibre responses. By contrast, using a similar protocol, application of DLH induced a steady discharge in the period preceding the electrical stimulation and also in between the A delta and C fibre responses, which were not themselves inhibited. 5. The negative heterotopic influences in normal rats during simultaneous immersion of the ipsi- and contralateral hindpaws was strongly reduced in rats with bilateral lesions of the dorsolateral funiculi at the cervical level (C3-C4). 6. It is concluded that strong negative interactions elicited by heterotopic noxious stimuli are observed in the spinoreticular system. Such interactions do not occur at the subnucleus reticularis dorsalis level but are mediated by supraspinal structures which control, through the dorsolateral funiculi, the spinal transmission of nociceptive information.

Animals↗

Responses of spinothalamic lamina I neurons to maintained noxious mechanical stimulation in the cat.

Noxious mechanical stimuli that are maintained for minutes produce a continuous sensation of pain in humans that augments during the stimulus. It has recently been shown with systematic force-controlled stimuli that, while all mechanically responsive nociceptors adapt to these stimuli, the basis for such pain can be ascribed to A-fiber rather than C-fiber nociceptors, based on distinctions in their respective response profiles and stimulus-response functions. The present experiments investigated whether similar distinctions could be made in subsets of nociceptive lamina I spinothalamic tract (STT) neurons using similar maintained stimuli. Twenty-eight lamina I STT neurons in the lumbosacral dorsal horn of barbiturate-anesthetized cats were tested with noxious mechanical stimuli applied with a probe of 0.1 mm(2) contact area at forces of 25, 50, and 100 g for 2 min. The neurons were classified as nociceptive-specific (NS, n = 14) or polymodal nociceptive (HPC, n = 14) based on their responses to quantitative thermal stimuli. The NS neurons had greater responses and showed less adaptation than the HPC neurons in response to these stimuli, and they encoded stimulus intensity better. Comparison of the normalized response profiles of all 28 nociceptive lamina I STT neurons, independent of cell classification, revealed 2 subgroups that differed significantly: "Maintained" cells with responses that remained above 50% of the initial peak rate during stimulation and "Adapting" cells with responses that quickly declined to <50%. The Maintained neurons encoded the intensity of the mechanical stimuli better than the Adapting neurons, based on ratiometric functions. A k-means cluster analysis of all 28 cells distinguished the identical two subgroups. These categories corresponded closely to the NS and HPC categories: Maintained cells were mostly NS neurons (10 NS, 3 HPC), and Adapting cells were mostly HPC neurons (4 NS, 11 HPC). Thus the present data are consistent with the distinctions between A-fiber and C-fiber nociceptors observed previously, because A-fiber nociceptors are the predominant input to NS lamina I STT neurons and C-fiber nociceptors are the predominant input to HPC neurons. These findings support the view that NS, but perhaps not HPC, lamina I STT neurons have a role in the pain caused by maintained mechanical stimuli and contribute to the sensations of "first" pain and "sharpness." Nonetheless, none of the units studied showed increasing responses during the stimuli, suggesting a role for other ascending neurons or forebrain integration in the augmenting pain produced by maintained mechanical stimulation.

Animals↗

Non-linearity of skin resistance response to intraneural electrical stimulation of sudomotor nerves.

Intraneural electrical stimuli (0.3 mA, 0.2 ms) were delivered via a tungsten microelectrode inserted into a cutaneous fascicle in the median nerve at the wrist in 16 normal subjects, and the effects on the sweat glands within the innervation zone were recorded as changes of skin resistance. In order to examine the relationship between the skin resistance level and the amplitude of transient resistance responses, trains of high frequency stimulation were used to reduce the skin resistance level and then transient resistance responses were evoked by single stimuli at 0.1 Hz. Regional anaesthesia of the brachial plexus in the axilla eliminated spontaneous sympathetic activity and reflex effects. At high skin resistance levels response amplitudes to single stimuli were low but they increased successively to a maximum at intermediate levels and then decreased again at low resistance levels. Repeated stimulation sequences evoked qualitatively similar response curves but quantitatively both response amplitudes and skin resistance levels were slightly reduced upon repetition. We suggest that the changes of response amplitudes are due to variable resistivity of the corneal layer. The shifts of the response curves with repetition of stimulation may result from increased hydration of the corneum. It is concluded that the variability of response amplitudes to constant stimuli makes the amplitude of a skin resistance response unsuitable as an indicator of the strength of sympathetic sudomotor nerve traffic.

Adult↗

Analysis of excitable cell activation: relative effects of external electrical stimuli.

In the functional electrical stimulation of nerve an expression defined as the 'activating function' has been introduced to evaluate the propensity for a particular fibre to excite. This approach to determine resulting activation is only an approximation as it neglects the presence of the fibres on the applied field, in contrast to activity determined from a rigorous solution to the core conductor/excitable membrane equations. An alternative approach to determining relative excitability based on the induced transmembrane potential is presented, thereby allowing for current redistribution via the space constant of the target fibre. The paper critically examines the approximations made with activating functions, and concludes that as currently formulated the activating function has limitations in predicting relative excitability under a number of important conditions. In contrast, it is the induced (passive) transmembrane potential that provides a quantitatively reliable estimate of the tendency for fibres to excite.

Electric Stimulation↗

Estradiol and progesterone influence the response of ventromedial hypothalamic neurons to tactile stimuli associated with female reproduction.

Stimulation of the vagina and cervix, provided by the male during copulation or manually with a probe, causes many behavioral and endocrine changes associated with female reproduction in rats. Previously, we found that vaginal-cervical stimulation (VCS), by mating or manual probing, increases the expression of Fos-immunoreactivity (Fos-IR) in discrete populations of neurons in the preoptic area, mediobasal hypothalamus and midbrain, suggesting that these neurons respond to VCS. The purpose of the present study was to determine if hormonal priming would increase the number of Fos-IR cells following VCS. Contrary to our hypothesis, in Experiment 1 priming animals with a behaviorally effective dose of 17 beta-estradiol benzoate followed 48 h later by progesterone caused a trend towards a decrease in the number of VCS-induced Fos-IR cells in the ventromedial hypothalamus. In Experiment 2, which was done to confirm this decrease in VCS-induced Fos-IR neurons by hormones, this effect was found to be statistically significant. Furthermore, this hormone-induced decrease in VCS-responsive cells was localized to the ventromedial nucleus of the hypothalamus, an area rich in estrogen and progestin receptors. No effects of hormone treatment on VCS-induced Fos-IR were observed in any other brain regions analyzed. These findings suggest that steroid hormones may elicit some of their effects on female reproductive behavior and physiology by altering the responsiveness of ventromedial nucleus neurons to vaginal-cervical stimulation.

Animals↗

A comparison of masking by visual and transcranial magnetic stimulation: implications for the study of conscious and unconscious visual processing.

Visual stimuli as well as transcranial magnetic stimulation (TMS) can be used: (1) to suppress the visibility of a target and (2) to recover the visibility of a target that has been suppressed by another mask. Both types of stimulation thus provide useful methods for studying the microgenesis of object perception. We first review evidence of similarities between the processes by which a TMS mask and a visual mask can either suppress the visibility of targets or recover such suppressed visibility. However, we then also point out a significant difference that has important implications for the study of the time course of unconscious and conscious visual information processing and for theoretical accounts of the processes involved. We present evidence and arguments showing: (a) that visual masking techniques, by revealing more detailed aspects of target masking and target recovery, support a theoretical approach to visual masking and visual perception that must take into account activities in two separate neural channels or processing streams and, as a corollary, (b) that at the current stage of methodological sophistication visual masks, by acting in more highly specifiable ways on these pathways, provide information about the microgenesis of form perception not available with TMS masks.

Consciousness↗

Renin-stimulating test in children.

Plasma renin activity (PRA) was measured after various stimuli to evaluate a renin-stimulating test and to screen suppressed PRA in 60 children with labile hypertension aged 10 to 14 years. There was a significant difference between supine PRA and that after both standing (for 15 or 60 minutes) or frusemide administration (P less than 0.001, respectively); however, there was no statistical difference between the PRA while standing or after frusemide. Children who gripped a hand dynamometer for three minutes did not show any change in PRA. Standing upright for 15 minutes or supine rest for 90 minutes after the administration of frusemide i.v. are easily applicable to children and seem the most appropriate renin-stimulating test in childhood. No subjects showed suppressed PRA in this study.

Adolescent↗

Controlling bursting in cortical cultures with closed-loop multi-electrode stimulation.

One of the major modes of activity of high-density cultures of dissociated neurons is globally synchronized bursting. Unlike in vivo, neuronal ensembles in culture maintain activity patterns dominated by global bursts for the lifetime of the culture (up to 2 years). We hypothesize that persistence of bursting is caused by a lack of input from other brain areas. To study this hypothesis, we grew small but dense monolayer cultures of cortical neurons and glia from rat embryos on multi-electrode arrays and used electrical stimulation to substitute for afferents. We quantified the burstiness of the firing of the cultures in spontaneous activity and during several stimulation protocols. Although slow stimulation through individual electrodes increased burstiness as a result of burst entrainment, rapid stimulation reduced burstiness. Distributing stimuli across several electrodes, as well as continuously fine-tuning stimulus strength with closed-loop feedback, greatly enhanced burst control. We conclude that externally applied electrical stimulation can substitute for natural inputs to cortical neuronal ensembles in transforming burst-dominated activity to dispersed spiking, more reminiscent of the awake cortex in vivo. This nonpharmacological method of controlling bursts will be a critical tool for exploring the information processing capacities of neuronal ensembles in vitro and has potential applications for the treatment of epilepsy.

Action Potentials↗

[Histochemical studies of the sensitivity of frog retinal cells to stimulus movement and flashes].

The technique of quantitative UV-cytophotometry of RNA was used for comparative study of the sensitivity of frog retina cells to the movement of stimuli and flashings. A corresponding set of stimulators which includes the movement of mounted stimuli and heterogenous flashings of diffuse light showed that a type of cells exists in the interior nuclear layer of the retina which is specifically sensitive to the movement. It is suggested that in the formation of this property a dynamic reciprocal lateral inhibition on the level between bipolar and amacrine cells takes place. Application of heterogenous flashing light allowed also to reveal functional variety of bipolar cells.

Animals↗

Inhibition and potentiation of T lymphocyte response to mitogens. Studies using two mitogenic stimuli simultaneously.

Rat thymocytes were stimulated with phytohaemagglutinin (PHA), Concanavalin A (Con A), pokeweed mitogen (PWM) and lipopolysaccharide (LPS) or with mixtures of two of these mitogens, added simultaneously to in vitro cultures. Four-five concentrations of first mitogen were matched with four-five concentrations of second mitogen, in all possible combinations. Synergistic effects were observed with LPS plus PHA and LPS plus PWM and inhibitory effects with PHA plus Con A and LPS plus Con A. The hypothesis is discussed that an inhibitory effects occurs when two mitogens react with identical or very similar receptors on the lymphocyte surface, while a synergistic effect is produced by two mitogens reacting with different receptors.

Animals↗

The use of visual stimuli during auditory assessment.

Two groups of male subjects beyond 50 years of age were given audiometric tasks with and without visual stimulation to determine if visual stimuli changed auditory perception. The first group consisted of 10 subjects with normal auditory acuity; the second, 10 with sensorineural hearing losses greater than 30 decibels. The rate of presentation of the visual stimuli, consisting of photographic slides of various subjects, was determined in experiment I of the study. The subjects, while viewing the slides at their own rate, took an audiotry speech discrimination test. Advisedly they changed the slides at a speed which they felt facilitated attention while performing the auditory task. The mean rate of slide-changing behavior was used as the "optimum" visual stimulation rate in experiment II, which was designed to explore the interaction of the bisensory presentation of stimuli. Bekesy tracings and Rush Hughes recordings were administered without and with visual stimuli, the latter presented at the mean rate of slide changes found in experiment I. Analysis of data indicated that (1) no statistically significant difference exists between visual and nonvisual conditions during speech discrimination and Bekesy testing; and (2) subjects did not believe that visual stimuli as presented in this study helped them to listen more effectively. The experimenter concluded that the various auditory stimuli encountered in the auditory test situation may actually be a deterrent to boredom because of the variety of tasks required in a testing situation.

Aged↗

Auditory brainstem and cortical responses following extensive transcranial magnetic stimulation.

The long term effects of transcranial electromagnetic stimulation (TEMS) on auditory brainstem and cortical evoked responses and on neuroanatomical structures in the auditory tract were investigated over a 12 month period in rabbits exposed to 1000 stimuli at 100% maximum stimulation level (2.0 tesla instrument output) with a clinical magnetic coil positioned over the cranium. (1) The tone and click audiograms of the pre and post TEMS-exposed plugged ears were normal and did not differ significantly, suggesting that the protected cochlea is unaffected by TEMS. (2) The mean absolute and interwave latencies of auditory brainstem evoked responses (ABR) and the peak amplitudes of the vertex positive waves P1, P3, and P4 in the exposed rabbits were within normal limits, and comparable those of the normal, pre-exposed animals. Wave P5 in the exposed animals was more variable and significantly different from the normal data in mean latency and amplitude. (3) The mean latencies and amplitudes of the post exposed cortical (late) auditory evoked responses (CAER) were not significantly different from the non-exposed ears. Light microscopic examination of sections of the cochlear nucleus and inferior colliculus, possible sources of waves P2 and P5, respectively, of the ABR, showed no EMS-related changes in cellular organization or histological damage. In conclusion, no deleterious effects of TEMS were observed on the protected ear or the peripheral and central auditory system of rabbits after extensive exposure to long term, high intensity, low frequency time-varying magnetic field stimulation with a clinical instrument.

Animals↗

A method of uroneurophysiological investigation in children.

Characteristics and reproducibility of bulbocavernosus reflex (BCR) and pudendal somatosensory evoked potentials (PSEP) elicited by mechanical stimulation in children were tested. Twenty-five male children aged 5-14 years without uroneurological complaints were enrolled in the study. In addition to electrical stimulation, a specially constructed electromechanical hammer triggered by an oscilloscope was used for mechanical stimulation of distal penis. All responses were detected by surface electrodes. The latencies and amplitudes of averaged as well as latencies of single BCR on single and double electrical stimuli were determined. Mechanical stimulation was described as much less unpleasant than electrical stimulation. Both mechanical/electrical stimulation elicited consistent and reproducible responses in high percentages of children (BCR: average, 80%/71%, single, 94%/100%; PSEP: 96%/96%, respectively). BCR latencies were significantly longer and PSEP amplitudes were significantly higher on mechanical stimulation. The compliance with mechanical was much better than with the electrical stimulation and the former can be recommended for clinical use. The effective mechanical stimulus delivered by a particular mechanical stimulator has a characteristic 'delay' (as to the actual point of triggering the oscilloscope ray) which influences the latency reading of responses; appropriate control data are therefore necessary.

Adolescent↗

Forms can be recognized from dynamic occlusion alone.

Direct and indirect theories of perception differ on whether form perception depends on higher order invariants or on features in the retinal image. The present paper describes a demonstration that an object can be recognized through a higher order pattern (dynamic occlusion) without any of the object's features being displayed. Stimuli consist of computer stimulations of black wireframe objects moving in front of, and occluding, a random layout of point lights on a black background. In this way, no single videoframe of the stimuli displays any of the object's features, and motion of the amodal object in front of the light points is necessary for the form to become visible. The forms can also be recognized when isoluminous colours are used for background and point lights. Finally, it is noted that, if the observer can actively control the motion of the object, e.g., by moving a computer mouse, recognition is enhanced as in Gibson's (1962) experiment on active touch.

Attention↗

In vivo quantification of muscle contractility in humans: healthy subjects and patients with myotonic muscular dystrophy.

The purpose of this study was to use direct in vivo contractility measurements to assess muscle function in patients with myotonic muscular dystrophy (MMD). The tetanic and twitch responses and several time parameters of muscle contraction were obtained from nine MMD subjects and nine able-bodied, age-matched controls. After a routine nerve conduction study, in vivo contractility measurements were obtained by stimulating the ulnar nerve at the wrist and recording the isometric flexor function of the intrinsic muscles at the metacarpophalangeal joint of the index finger. A series of single stimuli, paired stimuli, and fused tetanic stimulations were generated during a 20-minute experimental protocol. A stable tetanus was produced at 50Hz for 1.2 seconds. M-wave and contractile data were recorded at 1,000Hz by digitization of the analog signal and storage by the microcomputer. The MMD patients were weaker than controls (p less than .05), as shown by the 39% reduction in tetanic tension and 57% reduction in twitch tension. The MMD patients also had a significant impairment in relaxing their muscles as shown by the 1,100% increase in half-relaxation time after contraction, even though there was no evidence of repetitive firing after cessation of stimulus. These data show that MMD patients exhibit failure of sarcolemmal activation, altered excitation-contraction coupling mechanisms, and failure of the contractile machinery. The myotonia is due in part, to some defect in the contractile machinery; it is not solely due to failure of sarcolemmal activation.

Adolescent↗

Evoked potential components in the layers of the auditory cortex of the cat.

The intracortical distribution of evoked potentials was studied by seven-contact multielectrodes implanted into the primary auditory cortex of freely moving cats. The aim of the study was to compare the intracortical profiles of the responses evoked by click stimuli and by electrical stimulation of the medial geniculate body in different states of alertness and in Nembutal anesthesia. Only the early surface positive component showed phase reversal in the depth of the cortex. The middle latency components which were faithful indicators of vigilance appeared without phase reversal. Nembutal wiped out these components. A negative component of about 50 ms latency appeared in the attentive animal which had the highest amplitude close to the surface and decreased toward the depth indicating that it was generated in the most superficial layers of the cortex. The stimulation of the last nucleus of the specific auditory pathway elicited evoked potential patterns including also the middle latency components, which were closely similar to those induced by click stimuli.

Animals↗