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Attenuation of defensive threat and attack in wild rats (Rattus rattus) by benzodiazepines.

A battery of tests designed to elicit reactions to a variety of non-painful threat stimuli was used to study the effects of chlordiazepoxide (5-20 mg/kg), diazepam (1-5 mg/kg) and midazolam (1-10 mg/kg) on the defensive repertoire of wild Rattus rattus. The most consistent effect of benzodiazepine treatment, across compounds and tests, was a marked reduction in defensive threat and attack behaviors, with midazolam effective over a wider range of situations. In contrast, effects on freezing and flight reactions were more variable, differing substantially as a function of stimulus context. The general profile of observed changes in defense cannot be explained in terms of either non-specific behavioral suppression or a global reduction in defensiveness. Rather, our findings suggest that benzodiazepines may primarily induce a shift within the defense repertoire.

Aggression↗

Effect of phenytoin on the mental and physical function of patients with Baltic myoclonus epilepsy.

Progressive myoclonus epilepsy (PME) without Lafora bodies, or Baltic myoclonus epilepsy, is characterized by stimulus-sensitive myoclonus, generalized tonic-clonic seizures, and an irregularly progressive course beginning between 6 and 15 years of age. The EEG displays spike-and-wave paroxysms with irregular dominant activity. Baltic myoclonus epilepsy is a single-gene disorder inherited in an autosomal recessive pattern. Early cases were reported from Estonia, and many are now found in Finland, suggesting that the gene frequency is increased in those sharing the Finno-Ugric linguistic base. The use of phenytoin should be avoided in this disorder since its continued administration alone or with other antiepileptic drugs is associated with intellectual and motor deterioration, aggressive behavior, increasing ataxia, and even death. Treatment with valproate and the concomitant elimination of phenytoin have been associated with marked improvement in most cases. Baltic myoclonus epilepsy must be distinguished from Lafora body PME, which is relentlessly progressive and invariably fatal, but can usually be differentiated on clinical grounds.

Electroencephalography↗

The s-wave of the multifocal electroretinogram in cats.

PURPOSE: To characterize the s-wave of the multifocal electroretinogram (mfERG) in cats, and to determine the contribution of the inner retina to the s-wave by examining the effects of tetrodotoxin (TTX) and N-methyl D: -aspartate (NMDA) injected into the vitreous cavity. METHODS: mfERGs were recorded from 15 eyes of 15 male cats under general anesthesia. The stimulus consisted of 37 elements, and the luminance of the bright and the black elements were 200 and 4 cd/m2, respectively. The stimuli were presented in a pseudorandom binary m-sequence at six different base periods (bpds) from 13.3 to 426.7 ms. Fifty microliters of 7.0 microM TTX followed by 50 microl of 4.0 mM NMDA were injected into the vitreous cavity. RESULTS: The shape of the mfERGs in the cats resembled that in humans. The s-wave appeared on the descending limb of P1, as seen in human mfERGs, in 11 eyes, and the s-wave amplitude increased significantly as the bpd was increased. TTX and NMDA resulted in the disappearance of the s-wave at all bpds, while the amplitude of P1 remained unchanged. CONCLUSIONS: The s-wave is present in the mfERG in the cat, and its loss following injections of TTX and NMDA supports the view that the s-wave reflects the function of the ganglion cells and their axons.

Anesthetics, Local↗

Bilateral and multimodal sensory interactions of single cells in the pigeon's midbrain.

Standard microelectrode recording techniques were employed to monitor single unit activity in the pigeon's nucleus intercollicularis and medial substantia grisea et fibrosa periventricularis in response to visual, tactile and auditory stimuli. Approximately 40% of the units were driven exclusively by visual stimuli, 8% by tactile stimuli, 47% by both visual and tactile stimuli and a very small percentage by auditory stimuli. Visual receptive fields were generally excitatory in the contralateral eye and suppressive in the ipsilateral eye. Most units were movement selective and some demonstrated direction sensitivity, summation and habituation. Units were generally insensitive to stimulus shape or contrast reversal. Somatosensory receptive fields were located on both sides of the body and were either excitatory or suppressive or both. Ipsilateral visual and somatosensory bimodal inputs were most often of the same sign while ipsilateral visual and contralateral somatosensory bimodal inputs tended to be of opposite sign. Visual and somatosensory receptive field locations of bimodal units tended to be in register.

Animals↗

Taste responses to amino acids from facial nerve branches innervating oral and extra-oral taste buds in the channel catfish, Ictalurus punctatus.

Electrophysiological recordings were obtained from two branches of the facial nerve innervating oral and extra-oral taste receptive fields, respectively, in the channel catfish, Ictalurus punctatus. The results indicate that taste buds innervated by the ramus ophthalmicus superficialis (ros), innervating taste buds on the nasal barbel, and the ramus palatinus (rp), innervating taste buds on the anterior palate, have similar chemical specificities for amino acids. Among the amino acids tested, the most stimulatory compounds for both the ros and rp were L-alanine and L-arginine, having estimated electrophysiological thresholds of approximately 10(-9) M. Dose-response functions for amino acid stimuli recorded from both the ros and rp were power functions extending over 5 log units of stimulus concentrations. The general similarity in the nature of the taste input from spatially distinct gustatory areas supports a chemotactic role of the facial taste system in the channel catfish.

Adaptation, Physiological↗

The effects of grating complexity on transient evoked potentials.

In the present investigation, the effects of spatial frequency (1.0, 3.0 and 9.0 c/deg), grating complexity (1 + 3 or 3 + 9), and relative phase relationships (peaks-add or peaks-subtract) on the amplitude and latency of VEP components were examined with a pattern appearance (50 msec, 1.9 Hz) technique. The effects of temporally modulating one spatial component of a complex grating while the other component was continuously viewed were also investigated. Two components of the response obtained with pattern appearance were differentially affected by these stimulus manipulations. In general, most conditions that involved spatial complexity resulted in a loss of information that could be obtained when simple sine-waves were used.

Adult↗

Bacterial shock responses.

Bacteria, very early in their history, developed protective 'shock responses', triggered when the organism was exposed to some acute environmental stress. At the heart of each response was the accelerated synthesis of both general and stimulus-specified intracellular proteins. So successful was this strategy that its basic mechanism and several of its components were highly conserved throughout the course of evolution. This was particularly true of heat shock proteins whose universal distribution has both good and bad consequences for man.

Animals↗

1-(2,3-Methylenedioxyphenyl)-2-aminopropane (2,3-MDA): a preliminary investigation.

Rats trained to discriminate saline from either (+)-amphetamine, (+/-)-DOM, or (+/-)-3,4-MDA in a two-lever drug discrimination paradigm were administered doses of a novel positional isomer of 3,4-MDA, i.e. 2,3-MDA. The novel isomer produced neither amphetamine-appropriate nor DOM-appropriate responding: the 3,4-MDA stimulus did, however, generalize to 2,3-MDA.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗

Interleukin 6 production in fetal rat long bone cultures is correlated with PGE2 release and does not correlate with the extent of bone resorption.

Reports from several laboratories have suggested that interleukin 6 (IL-6) may play a role in the process of bone resorption. We have extended these studies by examining the role of IL-6 in fetal rat long bone (FRLB) resorption stimulated by a variety of agents, including parathyroid hormone (PTH); 1,25 dihydroxyvitamin D3 (1,25(OH)2D3); interleukin 1 (IL-1); tumour necrosis factor alpha (TNF-alpha) and lipopolysaccharide (LPS). This model of bone resorption does not require the generation of osteoclasts in order to elicit a resorptive response and allowed us to assess whether IL-6 can directly affect osteoclastic bone resorption. We confirmed previous studies which showed that exogenous recombinant murine or human IL-6 does not stimulate bone resorption and demonstrated that IL-6, when added prior to the addition of parathyroid hormone, caused a significant but somewhat variable inhibition at 120 hours. Exogenous PGE2 stimulated both IL-6 production and resorption in FRLB cultures in a concentration-dependent manner. Endogenous production of IL-6 in fetal rat long bone (FRLB) cultures was stimulus dependent and generally correlated with prostaglandin E2 (PGE2) levels in the same cultures. However, endogenous IL-6 production did not correlate with the extent of bone resorption, except when IL-1 and PGE2 were used as stimuli. Addition of indomethacin and diclofenac to IL-1 stimulated cultures demonstrated that both the IL-6 production and bone resorption were largely PGE-2 dependent. Neutralizing anti-IL-6 antibodies inhibited IL-6 activity in FRLB cultures but did not affect bone resorption, even in the IL-1 stimulated cultures.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Enhanced contrast sensitivity in auditory cortex as cats learn to discriminate sound frequencies.

To better understand the nature and time course for learning-induced cortical reorganization, we examined frequency-specific changes in auditory cortex as cats gradually improved at a difficult sound frequency discrimination task. Three adult cats were trained to discriminate between a tone pip at a fixed target frequency (S-) and a higher deviant frequency (S+). An adaptive training schedule led to an efficient estimate of the frequency discrimination threshold (FDT), which was used to track daily performance. Each cat was also implanted with an array of microwires in auditory cortex. Tone pips with different frequency and amplitude were used to map receptive fields. Onset responses were correlated with training time and the cat's ability to discriminate frequencies. Although lifetime of the neural implants varied among cats, each provided sufficient neural recording to relate at least 3 weeks of learning to response changes in the cortex. An improved FDT was associated with a differential decrease in response strength between the S- frequency and S+ frequencies. Response to the training frequencies gradually located in a local minimum compared to adjacent frequencies (p < 0.001, Cohen's d=0.50). Cortical changes were consistent with a theory of bimodal generalization that enhances stimulus classification by reducing similarity between reinforced and nonreinforced stimuli. Such a strategy may be especially appropriate during an early stage of learning to discriminate similar sounds and differ from later strategies required for fine discrimination.

Animals↗

Development of attentional allocation in the dual task paradigm.

Top-down control over attention was investigated on a dual task in 10-year-olds (N=15) and adults (N=21). The tasks were an auditory digit span (DS) and a simple visual response time (RT) task. In four conditions, participants performed neither (no-task), one (DS or RT only) or both tasks (dual). Dependent variables were DS accuracy, RT and pupillary dilation to digits as an estimate of mental effort. Children's behavioral and psychophysiological responses as a function of sequence length and stimulus position were generally similar to those of adults. Slopes of the functions relating pupillary dilation to memory load were linear and increasing in both groups, shallower in dual than that in DS only and shallower in children than that in adults. Children's behavioral results on the DS task began to diverge from those of adults as task demands shifted from passive retention to active rehearsal, but the children did not appear to try harder to compensate for a lower level of behavioral performance. Taken together, the findings suggest that although children allocated their attention in a similar manner as adults, their top-down control over attention in accordance with task difficulty was not yet fully mature.

Adolescent↗

Learning to tell apples from oranges.

Recognizing images requires sorting them into the correct perceptual categories. Without categories, apples could not be discriminated from oranges. A fundamental question is whether categories are innate or learned, and if learned, how well such discriminations generalize. A recent finding by Notman et al. demonstrates that certain categorical discriminations are learned fast but vanish for slightly rotated stimuli. Rather than higher "cognitive" learning, this indicates involvement of "early" mechanisms, which cannot generalize across different stimulus orientations.

Cognition↗

Evaluation of cortical excitability by motor and phosphene thresholds in transcranial magnetic stimulation.

Motor threshold (MT), as determined by transcranial magnetic stimulation (TMS), is used as a parameter of cortex excitability. In TMS with single or repetitive pulses, stimulus intensities in general are referred to the individual MT, although it is unclear whether MT also reflects the excitability of nonmotor cortical areas such as the visual cortex. Visual cortex excitability can be assessed by thresholds for eliciting phosphenes (phosphene threshold, PT) following TMS over the occipital cortex. The question of a different efficacy of TMS pulses in distinct cortical areas was approached by comparing motor and phosphene thresholds using single-pulse TMS applied to the primary motor and visual cortex. The aim of the study was to clarify, whether MT and PT correlate with each other and whether MT possibly serves as a reasonable measure for the excitability of the visual cortex. In 32 healthy volunteers, TMS with biphasic single pulses was applied over the motor and visual cortex with a figure of eight-shaped coil connected to a Dantec MagPro stimulator. MT and PT were individually measured (percent of maximal stimulator output). Mean PT (61.4+/-11.7%) was significantly higher than mean MT (39.4+/-5.9%) (p=0.01). MT and PT did not correlate significantly (r=0.29, p>0.1). These findings suggest that the MT does not reflect the excitability of the visual cortex. Regarding excitatory effects, the efficacy of TMS may be different over the motor and visual cortex, likely related to a different excitability of these cortical areas. This should be considered in planning and execution of TMS studies of nonmotor cortical areas.

Adult↗

Recovery of a temporally based visual discrimination after visual cortex lesion in the rat.

In Expt. 1, rats were conditioned to emit a shock avoidance response when the pulse rate of a light was increased. Then, after bilateral visual cortex lesions, the rats were given 10, 20, or 40 days recovery before relearning the discrimination. While all rats were able to relearn the discrimination response, lesion rats had a performance deficit after all recovery periods. Expt. 2 compared the effects of postoperative visual pulse rate training to those of auditory pulse rate training on relearning of the photic pulse-rate discrimination 10 days after visual decortication. Recovery of discrimination responding was better after auditory pulse rate training than after visual training. These data suggest that visual cortex lesions in the rat disrupt perceptual or associational functions involving the temporal features of a visual stimulus. In addition, generalization of relational properties during cross-modal training through multimodal CNS structures appears to enhance recovery of behavior after brain insult.

Acoustic Stimulation↗

Reduction of extracellular GABA in the mouse amygdala during and following confrontation with a conditioned fear stimulus.

In this study we examined conditioned fear-induced changes of extracellular gamma-aminobutyric acid (GABA) levels in the mouse amygdala with the in vivo microdialysis technique. Confrontation of freely behaving mice with a previously conditioned fear stimulus was accompanied by a pronounced reduction of extracellular GABA levels, indicative of a reduced GABA release and/or increased GABA uptake from the extracellular space. Reduced GABA levels were still observed in the amygdala several hours after the presentation of the conditioned stimulus. Moreover, stimulus-specific and generalized aspects of this GABA response could be distinguished according to their magnitude and time course in different behavioural groups. Our observations suggest that changes of GABAergic transmission may be involved in retrieval and expression of conditioned fear and the modulation of emotional state through the amygdala.

Acoustic Stimulation↗

Event-related skin conductance responses to musical emotions in humans.

While the reasons underlying musical emotions are unclear, music is nevertheless a powerful elicitor of emotion, and as such, may induce autonomic nervous system responses. One typical measure of this neural pathway is the skin conductance response (SCR). This response generally depends upon stimulus arousal, one of the two motivational determinants of emotion. The objective of the present study was to verify whether emotional reactions to music elicit such event-related autonomic responses. To this aim, four musical emotions varying in arousal were employed: fear, happiness, sadness and peacefulness. SCRs were found to be greater with the two more stimulating emotions, fear and happiness, as compared to the two more relaxing emotions, sadness and peacefulness (P<0.05). In addition, subjects' ratings of the emotional clarity for each excerpt did not parallel the corresponding SCRs magnitudes. The results show that SCRs can be evoked and modulated by musical emotional arousal, but are not sensitive to emotional clarity. While several studies have been performed with visual scenes and environmental sounds, the present study brings similar evidence from the musical domain.

Acoustic Stimulation↗

Information processing during sleep onset and sleep.

This Special Section examines the extent of information processing during sleep onset and sleep itself. It is generally agreed that, stimulus input is markedly inhibited during sleep, thus preventing conscious awareness of the external environment. Overt behavioural responses are rarely made within sleep. Two neurophysiological measures are therefore often used. The electrical activity of the brain (the EEG) can be employed to distinguish waking (conscious) from sleeping (unconscious) states. It is also possible to quantify the EEG prior to and following a detection (or a failure of a detection) of a stimulus. Such measures can thus be used to predict conscious awareness. A second measure that frequently has been employed is the brain's response to an external stimulus (the evoked potential). Different components of the evoked potential can be used to trace the extent of information processing during the different states of consciousness. Some are associated with a preconscious detection while others are associated with conscious awareness. Other evoked potentials may be unique to sleep.

Consciousness↗

[Quantitative assessment of the clinical electroretinogram].

The clinical application of electroretinography has been limited until now by the lack of standardisation, especially of stimulus conditions. Normal values for the electroretinographic response parameters can only be used if patients are examined under the conditions which were given for the examination of healthy subjects. It is shown in this paper that the inexpensive apparatus designed by Kooijman and Damhof (1981) can be calibrated by any user simply and at justifiable expense. Normal values for the amplitudes and peak times for the a- and b-wave are presented. The normal range of the values has been defined with regard to the frequency distribution. According to the authors' results, methods of descriptive statistics in skewed distributions are mainly necessary at low stimulus intensities. The descriptive methods for normal distributions were regularly applied at higher stimulus intensities. In general, however, ERG parameters are normally distributed as shown by the distribution of the residuals between the linear regression of the parameter to the logarithm of the corneal illuminance and the measured values. The influence of age on the amplitude was calculated according to the results of Lehnert and Wünsche (1966) and the lower limits of the normal range are given for four age groups. The data presented here may be used as normal values provided that the simple calibration methods are applied. Thus electroretinography is no longer a method merely for the laboratory, but can be used in clinics and offices as well. However, a prerequisite is that the physician has sufficient experience in ophthalmological electrophysiology.

Adult↗