Expression in paradoxical sleep of a conditioned heart rate response.

After a session of habituation to a tone, awake rats underwent two conditioning sessions during which the tone was paired with footshock. The tone alone was presented during paradoxical sleep (PS) following each session; it never awakened the animal. Heart rate (HR) was recorded at each tone presentation in wakefulness and PS. During conditioning in wakefulness, tone presentation elicited HR accelerative responses. Tone-evoked HR accelerations were also detected in PS following the two conditioning sessions. Such changes were not observed in rats that received unpaired presentations of tone and footshock. These results demonstrate that an HR conditioned response acquired in wakefulness can be expressed during PS.

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.

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.

Suppression of long-term potentiation induction during alert wakefulness but not during 'enhanced' REM sleep after avoidance learning.

Major learning events are typically followed by a period during which the number and/or duration of rapid-eye movement sleep episodes is increased. Processes critical to memory formation are thought to take place during this interval of 'enhanced' rapid-eye movement sleep. We therefore compared the capacity for long-term potentiation during rapid-eye movement sleep and alert wakefulness after learning. Rats were chronically implanted with electrodes for stimulation of the perforant path and recording of evoked potentials and EEG in the dentate gyrus. After obtaining baseline recordings, rats were trained on a 40-trial two-way active avoidance task. Conditioned rats exhibited a two-fold increase in the mean duration of rapid-eye movement sleep episodes, as reflected by a prolongation of the hippocampal theta rhythm. There was no change in the sleep pattern of pseudoconditioned controls, which received explicitly unpaired tones and foot shocks in a yoked design. High-frequency stimulation was applied during the second, third, and fourth major rapid-eye movement sleep episodes after active avoidance training. Another group was tetanized at matching time points during alert wakefulness. After pseudoconditioning, tetanus applied during wakefulness or rapid-eye movement sleep readily induced long-term potentiation, and there was no difference between groups in the magnitude of increase for the population excitatory postsynaptic potential slope or the population spike height as measured 1 h, 24 h, and 5 days post-tetanus.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.

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.

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.

Responses of hippocampal cells can be conditioned during paradoxical sleep.

To test the hypothesis that new associations can be acquired during sleep, we developed a conditioning paradigm in which both conditioned (CS) and unconditioned (US) stimuli were non-awakening intra-cerebral stimulations. The CS was a stimulation of the Medical Geniculate body and the US a stimulation of the Central Grey. An increase in hippocampal multiunit activity to CS was taken as the conditioned response. CS-US pairings were presented across 14 sessions, with 15 trials per session and a 24-h inter-session interval. Three groups were studied: in a group the CS-US pairings were given during the awake state (group W), and in two groups pairings were presented during sleep, either slow-wave sleep (group SWS) or paradoxical sleep (group PS). In the last group, to test the possibility of transfer to the awake state of the hippocampal response acquired in PS, the CS alone were presented interspersed with periods of wakefulness. Results showed that, before pairing, CS presentation induced no change in hippocampal multiunit activity in the three groups. After pairing, no hippocampal response to CS presentation occurred in SWS. In contrast, in the W group and in the PS group, a marked increase in hippocampal activity appeared to CS. The hippocampal response in the PS group developed progressively across sessions; it occurred only two sessions later than in the W group. Moreover, when the CS-evoked response reached the asymptotic level in PS, the presentation of CS alone in awake animals elicited the hippocampal response. These results suggest that a cellular conditioning can be established during PS and that the cellular conditioned response developed in PS can be transferred to the awake state.

Choice behavior of fornix-damaged rats in radial maze error-free situations and subsequent learning.

Fornix-damaged, sham-operated, and control rats were placed in a radial eight-arm maze for fixed series of runs with either a 0% or a 100% reinforcement schedule in order to study their choice behavior independently from any learning problem. Subsequently, the ability to learn the radial maze task was examined as a function of the exploratory patterns developed in each error-free situation. The results showed that the continuous absence or presence of food in the radial maze induced two distinct models of exploration in sham-operated and control rats: choice alternation in the absence of food and perseveration in the presence of food. Conversely, this dichotomy did not occur in fornix-damaged rats that run approximately the same number of paths in both error-free situations, but made fewer different path choices in the 0% reinforcement condition and more different path choices in the 100% reinforcement condition than controls. When submitted to the radial maze task, a positive transfer was observed in all groups from the error-free situation in which the rats run more different paths: from the 0% reinforcement situation for controls and from the 100% reinforcement situation for the lesioned rats. These data indicate that damaging the septo-hippocampal pathway modifies spontaneous choice behavior through a different response to specific reinforcement programs but does not prevent the memorization and the transfer of information from error-free to learning situations.

Clonidine reverses spatial learning deficits and reinstates theta frequencies in rats with partial fornix section.

Rats received knife-cuts to the dorsal fornix or sham-operations. Half of the animals from each group were injected with clonidine (0.01 mg/kg) and the others with saline before each daily trail of a 10-trial radial 8-arm maze task. The number of choices before the first repetition and the run time were used as performance indices. Lesioned rats were significantly impaired in the acquisition of this task. Clonidine-treated rats, lesioned or not, had an acquisition profile indistinguishable from that of sham-operated saline-injected rats, in spite of their increased run time. When tested one week after the last learning trial in a no-drug condition, lesioned rats treated with clonidine throughout learning maintained a high level of performance during the 5-day retraining phase. A parallel analysis of theta rhythms recorded in an independent group of rats placed in equivalent treatment and/or lesion conditions was then performed. Preoperatively, clonidine injections decreased theta frequency during both alert immobility and movement. Partial fornix lesions produced an increase in theta frequency. Finally, clonidine in fornix-damaged rats decreased theta frequency, thus reinstating the postoperative values at a level statistically no different from that recorded preoperatively. The role of clonidine in restoring the function of the septo-hippocampal input in partially fornix-damaged rats through a noradrenergic modulation of hippocampal acetylcholine release is discussed.

Parallel modifications of spatial memory performances, exploration patterns, and hippocampal theta rhythms in fornix-damaged rats: reversal by oxotremorine.

Learning scores and degrees of divergence of the exploratory patterns (EP) displayed during the acquisition stage of a radial eight-arm maze task were examined in fornix-damaged and sham-operated rats injected either with oxotremorine (0.1 mg/kg) or saline. Modifications of hippocampal rhythmic slow activity (theta) recorded in each condition were analyzed in CA1 and dentate gyrus. Dorsal fornix sections reduced choice accuracy but also induced the adoption of weakly divergent EP. Oxotremorine in animals with lesions reinstates both learning scores and degree of divergence of EP at the levels respectively observed in saline sham-operated animals. Finally, oxotremorine in sham-operated animals did not significantly improve choice accuracy but strongly modified the EP. Preoperatively, theta rhythms indicated a decrease of frequency after oxotremorine administration. Postoperatively, they showed an increase of frequency in animals with lesions that were reinstated at the preoperative level by oxotremorine.

[Facilitation of avoidance conditioning by reticular stimulation in the cat]. / Facilitation d'un conditionnement d'évitement par stimulation réticulaire chez le chat.

Learning is facilitated in Cats by posttrial reticular stimulation. It has been pointed out that this stimulation has no immediate anterograde effect and does not evoke any change in the cortical, motor or autonomic functions during its delivery. Moreover this stimulation has no effect on the time course of cortical and autonomic responses to the conditioned stimulus. Therefore, these results suggest that reticular stimulation has a specific action on memory consolidation or information processing.