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Biomedical subjects

R S Sainsbury

Publications and source records attributed to R S Sainsbury.

At least 19 recordsLinked to original sources

Effects of repeated hydrogen sulphide (H2S) exposure on learning and memory in the adult rat.

The effects of repeated exposure (125 ppm) of hydrogen sulphide (H2S) on learning and memory in the rat were investigated. A 16-arm radial arm maze (RAM) was used to examine neurobehavioural functioning in a series of three experiments. Experiment 1 involved training animals on a complex spatial maze task, prior to a 5-week period of exposure to H2S or a control gas mixture. Rats were tested for maze retention after each 5-day exposure period. It was determined that repeated H2S exposure had no effect on memory for a previously learned spatial task. Experiment 2 was conducted to determine whether H2S interferes with the acquisition of a novel spatial task. Naïve animals received daily maze training and exposure (H2S or control) sessions over an extended 11-week period (48 sessions). The results indicated that the groups were comparable on four of five measures of maze performance. H2S animals were impaired in their ability to find all of the reinforcers prior to the end of a trial, suggesting that H2S had an effect on performance rate, but not acquisition of the maze task. Finally, Experiment 3 was conducted to determine what role proactive interference might play in H2S-related brain impairment. Animals from the preceding experiment were trained on a new reversed contingency maze task. H2S animals made more overall arm entries than controls, suggesting that H2S may impair learning by increasing the animals' susceptibility to interference from irrelevant stimuli. The prefrontal cortex was discussed as a potential target site of H2S. The pathophysiological mechanisms underlying the effect of H2S on normal brain function have yet to be identified.

Administration, Inhalation↗

Hemispheric equivalence and age-related differences in judgments of simultaneity to somatosensory stimuli.

Hemispheric asymmetries, interhemispheric transfer time (IHTT), and age-related differences in judgments of simultaneity to tactile stimulation were examined. Two mechanical stimulators were employed to: (1) Determine whether both cerebral hemispheres are equally capable of processing fine tactile temporal information; (2) determine whether there is an age-related differential hemispheric decline in judgments of simultaneity, and (3) determine if simultaneity thresholds for tactile stimuli increase with advanced age. Tactile simultaneity thresholds were measured by using a modified parameter estimation by sequential testing algorithm. Participants judged whether pairs of tactile stimulation to index and middle fingers were delivered simultaneously. Results of both bimanual and unimanual conditions supported a model of hemispheric equivalence in that both hemispheres were equally capable of making judgments of simultaneity to fine tactile stimuli. The results further suggested that the hemispheric equivalence for judgments of simultaneity remains stable across adulthood. However, IHTTs of older adults were more than double that of younger adults, indicating a significant decrease in the speed of neural conduction. As well, relative to younger adults, older adults had significantly higher simultaneity thresholds.

Adult↗

Hippocampal theta: a sensory-inhibition theory of function.

The most prominent electrical signal which can be recorded from the hippocampus is called theta rhythm. Over the past 30 years there have been numerous attempts to relate this waveform to behavior. Theta has been associated with arousal, learning memory, attention, and most recently motor movement. While the relationship between one type of theta and certain kinds of movement is well established, a second type of theta shows no such relationship. In the present paper it is argued that the most parsimonious hypothesis relating theta to behavior is not the motor programming theory but a sensory-inhibition model. In this model theta is regarded as representative of general inhibition of systems not being used during motor behavior or alert immobility.

Animals↗

Effects of repeated exposures of hydrogen sulphide on rat hippocampal EEG.

Exposure to high levels of hydrogen sulphide (H2S) in humans has been associated with a number of respiratory and neurological symptoms. Acute toxicity following exposure to high concentrations is well-documented, however, there is little scientific information concerning the effects of exposure to low concentrations. The effects of low levels of H2S on electroencephalographic (EEG) activity in the hippocampus and neocortex were investigated on the freely moving rat (Sprague-Dawley). Hippocampal electrodes were implanted in the dentate gyrus (DG) and CA1 region. Activity was recorded for 10 min just prior to H2S exposure in the presence of air (pre-exposure). Rats were exposed to H2S (25, 50, 75, or 100 ppm) for 3 h/day; data was collected during the final 10 min of each exposure. The total power of hippocampal theta activity increased in a concentration-dependent manner in both DG and CA1; repeated exposures for 5 consecutive days resulted in a cumulative effect that required 2 weeks for complete recovery. The effects were found to be highly significant at all concentrations within subjects. Neocortical EEG and LIA (Large Amplitude Irregular Activity) were unaffected. The results demonstrate that repeated exposure to low levels of H2S can produce cumulative changes in hippocampal function and suggest selectivity of action of this toxicant.

Administration, Inhalation↗

Evolution of afterdischarge and seizure characteristics during electrical kindling of the guinea-pig.

Interspecies comparisons may help us understand the mechanisms which underlie brain plasticity. In this study, we examined the electrical kindling phenomenon in the amygdala, piriform and perirhinal regions of the guinea-pig. The changes in afterdischarge (AD) characteristics and behavioural seizures were assessed under different stimulation intervals and parameters as well as under reduced inhibitory neurotransmitter systems. We report that the guinea-pigs displayed a number of similarities with other species, such as the progressive increases in AD characteristics and seizure behaviours, but also a number of differences, such as the behavioural manifestations of the seizures, failing to reach a fully generalized tonic-clonic seizure and an apparent insensitivity to both low-frequency stimulation and reduced GABA and catecholamine levels.

Animals↗

Stimulation-induced RSA-like field activity in region CA1 of the hippocampal slice: amplitude maxima and topography.

In the present experiment RSA-patterned stimulation was applied to afferents in the CA1 region of the hippocampal slice preparation and depth profiles of the resultant field activity were performed. RSA-patterned stimulation applied to the stratum lacunosum-moleculare region resulted in field activity through the CA1 region with similar morphology, phase, and amplitude profiles to the type 1 RSA profile found in vivo. In contrast, RSA-patterned stimulation applied to the stratum oriens and midstratum radiatum regions did not result in field profiles characteristic of the RSA recorded in vivo. The results of the present study confirm predictions made by previous modelling experiments and CSD analyses performed in the freely moving animal, which suggest that the type 1 RSA profile is primarily the result of distal excitation onto CA1 pyramidal cells.

Afferent Pathways↗

Alpha 2 modulation of type 1 and type 2 hippocampal theta in the freely moving rat.

In order to determine the brain sites involved in the noradrenergic modulation of hippocampal theta, the alpha 2 agonist detomidine was infused into one of three brain sites in the freely moving animal: hippocampus, median raphe nucleus (MRN), or locus coeruleus (LC). Bilateral hippocampal recording electrodes were implanted in 45 animals. Infusions of detomidine into the hippocampus produced an attenuation of type 1 (movement) theta. Detomidine infused into the MRN produced a release of type 2 (immobility) theta, although having no effect on type 1 theta. No significant changes were noted in the hippocampal EEG activity following infusions of detomidine into the LC. Infusions of Xylocaine into each of the above brain sites were ineffective in eliciting changes in hippocampal EEG activity. No behavioral effects were noted following infusions of detomidine or Xylocaine. The present results suggest that the attenuation of type 1 theta occurs at the hippocampus, while the release of type 2 theta occurs at the MRN.

Analgesics↗

Alpha 2-noradrenergic modulation of hippocampal theta activity.

The purpose of the present study was to determine the role of norepinephrine in the generation of hippocampal theta activity. Experiments were performed on urethane-anesthetized rats, implanted with recording electrodes in the dentate gyrus and stimulating electrodes in the dorso-medial posterior hypothalamus. The effects of norepinephrine on hippocampal theta activity was studied by directly infusing norepinephrine and other noradrenergic agents into the hippocampus. Norepinephrine microinfusion produced a decrease in the amplitude of theta activity as observed in the polygraph chart record. Subsequent spectral analyses demonstrated a decrease in power at peak theta frequencies, as well as a decrease in power at frequencies between 20-25 Hz (noise). The inhibitory effect of norepinephrine on hippocampal type 2 theta activity was found to be mediated by alpha 2-adrenergic receptors. Microinfusions of an alpha 2 agonist (detomidine) mimicked the effects produced by norepinephrine, whereas alpha 1 and beta agonists were ineffective. The inhibitory effect of detomidine was blocked by microinfusions of an alpha 2 antagonist (tolazoline), which indicates that the site of action was specific to the noradrenergic alpha 2 receptor.

Adrenergic alpha-Agonists↗

The effects of alpha 2 agonists and antagonists on hippocampal theta activity in the freely moving rat.

The alpha 2 agonists detomidine and xylazine were given to freely moving rats implanted with bilateral hippocampal recording electrodes. These alpha 2 agonists produced virtually continuous type 2 (immobility) theta. Type 1 (movement) theta was attenuated with these drugs. Subsequent administration of atropine sulfate eliminated all theta in the hippocampus. Other animals were given the alpha 2 antagonist tolazoline. This drug had no effect on type 1 theta but animals showed an increase in the production of type 2 theta during sensory stimulation. These type 2 theta responses habituated both within and between trials. Tolazoline was ineffective as a blocking agent for the effects of detomidine. Preadministration of atropine sulfate blocked the effects of detomidine on type 2 theta but not on the elimination of type 1 theta. Results are discussed in terms of alpha 2 modulation of the cholinergic and serotonergic systems.

Adrenergic alpha-Agonists↗

The role of the pontis oralis in the generation of RSA activity in the hippocampus of the guinea pig.

The relationship between field activity in the nucleus pontis oralis (PnO) and the hippocampus was examined in the guinea pig. Rhythmical slow activity (RSA or theta activity) could be recorded from both the pontis oralis and the hippocampus. RSA recorded in the pontis oralis was of the same principal frequency as that found in the hippocampus, but had a much lower amplitude. Behavioral correlates of PnO RSA were the same as the behavioral correlates of hippocampal RSA. The effects of atropine sulfate on RSA were the same at each site. Stimulation of the PnO produced RSA in the hippocampus. Lesions of the PnO had no effect on RSA recorded from the hippocampus or on the behavioral correlates of this RSA. Lesions of the medial septum abolished RSA in both sites. Cross-correlations between field activity recorded from both the hippocampus and PnO showed the same time lag before and after septal lesions. These results indicate that while the PnO is not instrumental in the production of hippocampal RSA, an intact septum is necessary for the production of RSA in both sites. They also indicate that there is a common projection to these sites which does not pass through the medial septum.

Animals↗

Attentional set in pure- versus mixed-lists in a dichotic listening paradigm.

An experiment was designed to assess the contribution of attentional set to performance on a forced choice recognition task in dichotic listening. Subjects were randomly assigned to one of three conditions: speech sounds composed of stop consonants, emotional nonspeech sounds, or a random combination of both. In the groups exposed to a single class of stimuli (pure-list), a REA (right ear advantage) emerged for the speech sounds, and a LE (left ear advantage) for the nonspeech sounds. Under mixed conditions using both classes of stimuli, no significant ear advantage was apparent, either globally or individually for the speech and nonspeech sounds. However, performance was more accurate for the left ear on nonspeech sounds and for the right ear for speech sounds, regardless of pure versus mixed placement. The results suggest that under divided attention conditions, attentional set influences the direction of the laterality effect.

Adult↗

Modality specific type 2 theta production in the immobile rat.

The purpose of the present study was to compare the relative effectiveness of stimulation of different sensory modalities in eliciting Type 2 theta in the rat in the presence or absence of a ferret. Visual, auditory, and tactile stimuli were presented to rats in both conditions. Tactile stimulation produced more movement than either visual or auditory stimuli when the ferret was present. In both conditions, however, more Type 2 theta was observed in response to tactile or visual stimulation than to auditory stimulation. In the arousal condition, stimulation of tactile and auditory modalities resulted in significant increases in the amount of Type 2 theta produced. Input to the visual modality produced high levels of Type 2 theta production in both low- and high-arousal conditions. It is argued that Type 2 theta is not necessarily a precursor to movement but rather sensory processing while in a high state of arousal.

Animals↗

Sensitization and hippocampal type 2 theta in the rat.

Previous research has consistently demonstrated that there are two types of theta which can be recorded from the hippocampus of a variety of species. Type 1 theta occurs during voluntary movements such as walking, running and rearing while type 2 theta occurs during alert immobility. Large amplitude irregular activity (LIA) occurs during more automatic behaviors such as grooming and chewing as well as during non-alert immobility. Type 2 theta can be readily elicited in the unrestrained guinea pig and rabbit. While spontaneous type 2 theta rarely occurs in the rat, short trains of type 2 theta have been observed during conditioning. The purpose of the present study was to examine the relationship between type 2 theta and inescapable shock when the temporal characteristics of the conditioning stimulus (CS) were varied. Three conditioning paradigms (delay, trace, random) were utilized. Type 2 theta production increased over time as a function of the number of shocks and was not due to conditioning. There were no differences in the three groups in the occurrence of type 2 theta during CS presentations or during the inter-stimulus intervals. Previously neutral sensory stimulation also produced type 2 theta after conditioning in all groups. The inescapable shocks placed the rat in a high state of arousal which subsequently sensitized the animal to produce type 2 theta. The data was used to support the hypothesis that a state of arousal is a necessary precursor for the production of type 2 theta.

Acoustic Stimulation↗

Behavioral correlates of hippocampal type 2 theta in the rat.

Previous research has indicated that there are two types of theta activity which can be recorded from the hippocampus in most rodents. One type (type 1) of theta is correlated with voluntary movements while the second (type 2) occurs during immobility. A third waveform termed LIA (Large Amplitude Irregular Activity) occurs during more automatic behaviors, e.g., grooming, shivering or immobility. In the rabbit and guinea pig type 2 theta can readily be elicited in unrestrained animals. However, type 2 theta is rarely seen in the unrestrained rat. The purpose of the present study was to determine the stimulus conditions that are necessary for the elicitation of type 2 theta in the rat. In the present study 20 unrestrained rats were observed in the presence of a cat or a ferret. Movements by the cat or ferret produced theta in immobile rats. Sensory stimuli which did not ordinarily produce type 2 theta would reliably do so in the presence of the cat or ferret. It is hypothesized that type 2 theta in the unrestrained immobile rat occurs during sensory processing but only when the animal is in a high state of "arousal."

Acoustic Stimulation↗

Hemispheric asymmetry in the perception of emotional sounds.

Three experiments were conducted to investigate hemispheric asymmetry for the perception of emotional sounds. Pairs of human nonspeech sounds were presented dichotically in a forced choice recognition task. Under divided attention conditions (Experiments 1 and 2) an left ear advantage (LEA) emerged during the second block of trials. Performance accuracy for the left and right ears was equal during the first block of trials. Under selective attention conditions (Experiment 3) an LEA emerged during the first block of trials. The results suggest that attention influences the rate of development of the laterality effect but not the direction of the effect.

Adult↗

The effects of entorhinal cortex lesions on type 1 and type 2 theta.

The effects of bilateral entorhinal cortex lesions on type 1 and type 2 theta generation in the guinea pig were studied in the chronic preparation. EEG recordings from dentate generator zones demonstrated a decrease in the relationship between ongoing type 1 motor movements and theta generation. Before lesioning theta activity accompanied type 1 behaviors (i.e., walking and head movements) in 100% of the samples, while subsequent to lesioning theta activity was present in only 58% of the samples. In addition, prior to lesioning, type 2 theta was present in 100% of the samples taken during immobile sensory processing, e.g., tactile stimulation, while after lesioning type 2 theta was present in only 34% of the samples. Type 2 theta is selectively sensitive to disruption by atropine sulfate. In the present experiment atropine sulfate eliminated all theta activity after entorhinal lesions. Consequently as no type 1 theta appeared to be present it was argued that the entorhinal cortex is a critical route for type 1 theta. However, as the behavioral and sensory correlates of both type 1 and type 2 theta were disrupted it was suggested that the entorhinal cortex is an integral part of both systems.

Animals↗

The relationship between type 2 theta and behavior.

Although there is extensive literature on the correlation between Type 1 theta activity in the hippocampus and behavior, little is known about the behavioral correlates of "Type 2" (immobility) theta. In the present study, guinea pigs were exposed to three high "arousal" situations. These situations produced reliable trains of "Type 2" theta. Atropine sulfate abolished "arousal" and Type 2 theta. In the second study, we determined whether the Type 2 theta response was produced by specific stimuli or by a generalized sensitization to incoming sensory stimuli created by the testing situation. In this study, a stimulus which had not previously elicited Type 2 theta was presented a second time after a presentation of a stimulus which did elicit Type 2 theta. The previously neutral stimulus now elicited Type 2 theta. These results were interpreted within an "arousal" theory framework.

Animals↗