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B Hars

Publications and source records attributed to B Hars.

18 recordsLinked to original sources

Endogenous nitric oxide in the rat pons promotes sleep.

Pontine cholinergic structures are known to play a key role in the regulation of vigilance states associated with desynchronised EEG, i. e., wakefulness and paradoxical sleep. As the cholinergic cells of these nuclei, the pedunculopontine tegmentum (PPT) and the laterodorsal tegmentum, are enriched with nitric oxide synthase (NOS), we tested the hypothesis that nitric oxide (NO) in the pons is implicated in wake and sleep regulation. For this reason, a NOS inhibitor, a NO precursor and a NO donor were injected in the PPT of rats. Vigilance states were recorded for 6 h following the injections. Quantification of vigilance states after drug injections were compared to those obtained in control conditions. It appeared that the NO donor had a slight effect on vigilance states, but the NOS inhibitor decreased sleep and inversely the NO precursor increased sleep. These results show for the first time in the rat that a NOS inhibitor, injected directly into the PPT, is able to reduce sleep and that a NO precursor had the opposite effect. They suggest that endogenous NO production in the PPT has a somnogenic effect. The participation of endogenous NO in vigilance regulation is discussed in light of the role attributed to pontine cholinergic system in wakefulness and sleep.

Anilides↗

Chronic, low-level exposure to the cholinesterase inhibitor DFP. II. Time course of behavioral state changes in rats.

Rats were repeatedly administered with low doses of diisopropylfluorophosphate (DFP; 0.2 mg/kg/day, SC), an irreversible cholinesterase (ChE) inhibitor. Control rats received a daily injection of oil vehicle or of saline. Recordings of the sleep-wake states were obtained in the 6 h following 1, 3, 6, 9, 13, 17, and 21 injections, as well as 2, 4, and 19 days after 9-day treatment. DFP administration increased waking at the expense of slow-wave sleep (SWS), but not of paradoxical sleep (PS); as a result, the PS/SWS ratio was strongly enhanced. These changes developed across days, were maximal after six to nine injections, and were then maintained at that level until cessation of treatment. This time course of behavioral state alterations paralleled the time course of ChE inhibition in the mesopontine cholinergic nuclei and the pontine reticular formation described in the companion article. In contrast, after DFP withdrawal, behavioral states returned to control values more rapidly (in 2-4 days) than did ChE activity. These results are discussed regarding the promoting role of cholinergic neurotransmission in brain-activated states.

Animals↗

Chronic, low-level exposure to the cholinesterase inhibitor DFP. I. Time course of neurochemical changes in the rat pontomesencephalic tegmentum.

Rats were repeatedly administered with a low dose of diisopropylfluorosphosphate (DFP; 0.2 mg/kg/day, SC, for 9 or 21 days), an irreversible cholinesterase (ChE) inhibitor. Control rats received a daily injection of oil vehicle. Neurochemical changes occurring in the pontomesencephalic tegmentum (PMT), a brain stem region critically involved in behavioral state control, were evaluated at various times of treatment and after DFP withdrawal. First, enzyme assay revealed a profile of ChE inhibition in the whole PMT which looked like that observed in the striatum; both the inhibition and recovery proceeded more slowly than they did in the plasma. Second, quantitative histochemistry indicated that ChE activity in the mesopontine cholinergic nuclei and the pontine reticular formation progressively decreased across the first days of DFP exposure, to reach an asymptotic level of inhibition after 6 days (74-82% inhibition). The inhibition was less pronounced in the locus coeruleus (49%). Third, [3H]QNB autoradiography showed that muscarinic receptor density was unchanged in any of the PMT areas selected. These results are discussed regarding the question of regional variation in susceptibility to anti-ChE agents. To what extent behavioral state alterations occur concomitantly with ChE activity changes is assessed in the companion article.

Animals↗

Neuronal plasticity induced by fear conditioning is expressed during paradoxical sleep: evidence from simultaneous recordings in the lateral amygdala and the medial geniculate in rats.

The lateral amygdala (LA) and its afferent connections from the medial geniculate (MG) play a pivotal role in auditory fear conditioning. The authors evaluated whether those neurons could express in paradoxical sleep (PS) physiological plasticity acquired in waking. After a habituation session, rats received tone-footshock pairings in 3 sessions. After each session, the tone alone was presented during PS episodes. Multiunit activity was simultaneously recorded in the LA and the medial part of the MG. Both in LA and MG, conditioned responses emerged rapidly (within 5 trials), were expressed with short latency (<20 ms), and were maintained in PS after training. Such changes were not observed in pseudoconditioned rats. These results are discussed regarding the question of the primary sites of plasticity in auditory fear conditioning and regarding the functional significance of preserved expression in PS of learning-induced neuronal plasticity.

Acoustic Stimulation↗

Pontine microinjection of carbachol does not reliably enhance paradoxical sleep in rats.

It has been repeatedly shown in cats that acute administration of carbachol into the pontine reticular formation (PRF) readily evokes a state that closely mimics natural paradoxical sleep (PS). Surprisingly, there are few corresponding studies in rats. In order to further characterize the effects of pontine carbachol in rats, 151 injections of different doses (from 3 micrograms to 0.005 microgram in 0.1 microliter saline) of carbachol were made at different sites within the PRF of 70 rats. Sleep-waking states obtained in the 4 hours following carbachol administration were compared to control values, obtained both under baseline condition (no injection) and following pontine injection of 0.1 microliter saline. On the one hand, from the whole set of carbachol injections, it appeared that: 1) most injections (112/151) did not significantly alter the sleep-wake states; 2) when carbachol was effective, it induced either increased PS (20 injections) or increased waking (19 injections); and 3) effective injection sites were intermingled with noneffective sites. Dose- or site-dependency effects can account in part, but not totally, for these discordant results. On the other hand, in accordance with previous rat studies, we found that: 1) the PRF medial and ventral to the motor trigeminal nucleus was the most effective region for carbachol to increase PS; 2) carbachol-induced PS enhancement was of moderate magnitude (+60% above control saline level over the 4-hour recording time); 3) latency to onset of the first PS episode was not shortened; and 4) only the number of PS episodes was increased, their duration was not prolonged. These characteristics of carbachol-induced PS enhancement strongly differ, both in terms of magnitude and timing, from those described in cats. We suggest that the less reliable and weaker effects of pontine carbachol injection in rats compared to cats can be due to methodological problems inherent in the intracerebral microinjection technique and also to species-related differences in the mechanisms controlling the PS state.

Animals↗

Non-awaking basal forebrain stimulation enhances auditory cortex responsiveness during slow-wave sleep.

Unilateral basal forebrain (BF) stimulations were delivered during slow-wave sleep (SWS) while multi-unit recordings were performed bilaterally in the auditory cortex. Ten tone presentations were followed by 10 pairing trials between BF stimulation and tone. Non-awaking BF stimulations facilitated the tone-evoked responses ipsilaterally only. Atropine blocked the facilitation of the ipsilateral evoked responses observed after pairing in wakefulness. Thus, non-awaking cholinergic input can enhance cortical responsiveness during SWS.

Acoustic Stimulation↗

Transient and prolonged facilitation of tone-evoked responses induced by basal forebrain stimulations in the rat auditory cortex.

We investigated the relationships between cortical arousal and cholinergic facilitation of evoked responses in the auditory cortex. The basal forebrain (BF) was stimulated unilaterally, while cluster recordings were obtained simultaneously from both auditory cortices in urethane-anesthetized rats. The global electroencephalogram (EEG; large frontoparietal derivation) and the local EEG (from the auditory cortex) were recorded. The BF was stimulated at two intensities, a lower one which did not desynchronize the EEG and a higher one which did. Twenty pairing trials were delivered, during which a tone was presented 50 ms after the end of the BF stimulation. At low intensity, the pairing procedure led to a transient increase in the ipsilateral tone-evoked responses. At high intensity, the pairing increased the ipsilateral evoked responses up to 15 min after pairing. Such effects were not observed for the contralateral recordings. Systemic atropine injection prevented the facilitations observed ipsilaterally. BF stimulations alone did not induce any increased evoked response either at low or at high intensity. These results show (1) that a tone, presented while the cortex is activated by cholinergic neurons of the BF, evokes enhanced cortical responses, and (2) that the duration of this facilitation is dependent on the stimulation intensity. These results are discussed in the context of neural mechanisms involved in general arousal and cortical plasticity.

Acoustic Stimulation↗

Basal forebrain stimulation facilitates tone-evoked responses in the auditory cortex of awake rat.

The effects of unilateral basal forebrain stimulation on the tone-evoked responses recorded in the auditory cortex ipsilateral and contralateral to the stimulation site, were investigated in fully awake rats. After 10 tone alone presentations, 20 pairing trials were given during which the basal forebrain stimulation was followed by the tone 30 ms later. Ten test-tones were presented immediately, 15 min and 1 h after pairing. Immediately after pairing, the short-latency "on" and "off" tone-evoked responses were enhanced in the ipsilateral but not in the contralateral cortex. This enhancement did not persist 15 min later. Systemic atropine injection prevented the ipsilateral facilitation. The responses to the tone were not modified when tested after 20 basal forebrain stimulations delivered in the absence of the tone. These results are the first demonstration in awake animals that an activation of the auditory cortex by cholinergic neurons of the basal forebrain is able to facilitate cortical responsiveness. A temporal contiguity between the cholinergic activation and the neuronal discharges elicited by the sensory stimulus is required for the facilitation to take place. The results are compared to previous ones obtained in anesthetized animals, and the functional role of cholinergic activation from the basal forebrain in cortical processing is discussed.

Acoustic Stimulation↗

Learning-induced plasticity in the medial geniculate nucleus is expressed during paradoxical sleep.

Fear conditioning to an acoustic stimulus produces increases in tone-evoked discharges of neurons in the medial division of the medial geniculate nucleus (MG). This study examined the responses of MG neurons to a conditioned tone presented in paradoxical sleep (PS). After 1 session of habituation to a tone, awake rats underwent conditioning in 3 sessions during which the tone was used as the conditioned stimulus preceding a footshock. Control rats received unpaired presentations of tone and shock. The same tone, which never awakened the animal, was presented during PS following each daily session. Responses of MG neurons to the tone in PS were increased after conditioning. This enhancement was as large as that in waking and was manifested earlier after tone onset than in waking. No change appeared after pseudoconditioning. These results demonstrate that associatively induced plasticity in the MG can be expressed during PS.

Acoustic Stimulation↗

Improvement of learning by mesencephalic reticular stimulation during postlearning paradoxical sleep.

Evidences have been given which suggest that a newly formed memory trace is processed during paradoxical sleep (PS) following learning. The present experiments were aimed at testing the hypothesis that during postlearning PS the new memory trace is in a similar state as immediately after acquisition. For this purpose, a mild electrical stimulation of the mesencephalic reticular formation (MRF)--known to enhance retention performance when delivered just after learning--was administered during postlearning PS phases. Wistar rats were trained to run in a six-unit spatial discrimination maze for food reward. After each daily trial, extradural cortical electrodes (ECoG) activity was monitored polygraphically for 4 h. Half of the animals received nonawakening MRF stimulations during the first six phases of PS. Control rats received no stimulation. The learning results showed a marked improvement in performance, in terms of error number reduction, in the stimulated group. Results of a second experiment confirmed the facilitative effect of MRF stimulations given during postlearning PS. Moreover, they emphasized the specific role of PS, by showing that the same stimulations were ineffective when delivered, at the same time intervals after training, during six periods of waking or six periods of slow-wave sleep. These results lend support to the idea of a reactivation of the new memory trace during PS. They suggest that dynamic processes, similar to those immediately following acquisition or exposure to a reactivating treatment (i.e., a reminder), take place during postlearning PS.

Animals↗

Impairment of learning by cueing during postlearning slow-wave sleep in rats.

Rats were trained in a two-way shuttle avoidance task, 20 trials per day for 3 consecutive days. The conditioned stimulus preceding a footshock was an ear shock in expt. 1, it was a tone in expt. 2. In both experiments, experimental animals received non-awakening ear shocks during 6 periods of slow-wave sleep (SWS) following each conditioning session. Control animals received no ear shock during SWS. Results showed that ear shocks delivered during SWS impaired subsequent learning performances only in expt. 1, i.e. when they were relevant to the learning task and could act as a reminder treatment.

Animals↗

Is increase in post-learning paradoxical sleep modified by cueing?

Rats were submitted to three sessions of an active avoidance conditioning. The conditioned stimulus (CS) was either an ear shock or a tone. Sleep was measured after each session. Experimental animals received non-awakening ear shocks during post-learning paradoxical sleep (PS). When ear shocks were the CS and were subsequently used as cues during PS, PS increases were observed, but they displayed 2 unusual characteristics: they were due to longer average size of PS phases rather than to higher number of phases as usually; PS did not return to baseline level even when learning seemed to be achieved. By contrast, when ear shocks were not associated with conditioning, animals shocked during PS exhibited the usual PS increases.

Animals↗

Improvement of learning by cueing during postlearning paradoxical sleep.

Rats were submitted to an active avoidance conditioning in a shuttle box with slight ear shocks used as conditioned stimulus (CS) preceding a foot shock. Three conditioning sessions were performed with a 24 h intersession interval. Animals were divided into 3 groups. After each session, the first group received the CS as cue during the first 6 phases of paradoxical sleep (PS) following learning. The second group received the CS as cue during 6 periods of wakefulness. The third group received no cue. Animals cued during PS showed a significant improvement in performances. The effect of cueing during the awake state appeared to be marginal compared to the clear-cut effects when the cue was presented during PS. A control experiment showed that the same ear shocks presented during PS were ineffective when they were not associated with the learning task (in this experiment a tone was used as CS during conditioning). These results are discussed in terms of memory reactivation during postlearning paradoxical sleep.

Animals↗

Reminder abolishes impairment of learning induced by paradoxical sleep retardation.

Rats were submitted to one daily trial in a relatively complex maze. When sleep was delayed (by the water tank technique) for 180 min after each trial, learning was impaired. A reminder treatment (90 sec exposure to contextual cues) immediately before each trial, counteracted the effects of sleep deprivation. The reminder did not in itself contain sufficient information to facilitate performance of non sleep delayed animals. These results suggest that a retrieval failure is involved in memory impairment caused by post-learning paradoxical sleep deprivation.

Analysis of Variance↗

Reticular stimulation facilitates retrieval of a 'forgotten' maze habit.

Rats tested 25 days after training in a complex maze showed significant forgetting. Stimulation of the mesencephalic reticular formation immediately prior to retention testing facilitated performance in that stimulated rats made fewer errors (but did not run faster) than non-stimulated controls. Rats exposed to a contextual cue as a reminder before testing ran faster and made fewer errors than controls. Results are discussed in terms of forgetting being due to retrieval failure, and the reticular stimulation facilitating retrieval of information concerning the spatial configuration of the maze.

Animals↗

Processing of learned information in paradoxical sleep: relevance for memory.

After a short review of the post-learning paradoxical sleep (PS) deprivation effects and of the PS changes induced by learning, we present a set of electrophysiological and behavioural experiments showing that: (1) processing of relevant information is possible during PS; (2) new associations can be formed during PS; (3) previously learned information can be reprocessed during PS; and (4) the effects of information processed during PS can be transferred to the awake state and be expressed in behaviour. Altogether, these results support the idea that dynamic processes occurring during post-learning PS can contribute to the effectiveness of memory processing and facilitate memory retrieval in wakefulness.

Animals↗

A new system for computer aided dental identification in mass disasters.

In recent years, several computer programs for dental identification in mass disasters have been developed. Unfortunately, it may be difficult to get access to such programs. The Norwegian police presently utilizes a text retrieval program, NOVA*STATUS, for detection work. This program is based on the British STATUS ONE program, and it enables the user to find from a large pool of postmortem dental registration one or several sets containing specific information about one tooth or several teeth. The complete relevant set(s) can be displayed for visual examination and comparison. A coding system for dental information has been developed as well as a system for interrogating the computer. This system and its efficiency have been tested on a simulated small scale disaster where various well-known difficulties in dental identification were included.

Computers↗