Elizabeth Hennevin

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.

Muscimol Diffusion after Intracerebral Microinjections: A Reevaluation Based on Electrophysiological and Autoradiographic Quantifications ☆

Intracerebral muscimol injection is widely used to inactivate discrete brain structures during behavioral tasks. However, little effort has been made to quantify the extent of muscimol diffusion. The authors report here electrophysiological and autoradiographic results obtained after muscimol injection (1 microg/microl) either into the nucleus basalis magnocellularis (0.1-0.4 microl) or into the thalamic reticular nucleus (RE, 0.05-0.1 microl). In 52 rats, multiunit recordings were collected either in the RE or in the auditory thalamus during the 2 h following muscimol injection. Decreases in neuronal activity were observed up to 3 mm from the injection site; their time of occurrence was a function of the distance between the injection and recording sites. Because these decreases cannot be explained by physiological effects, they likely reflected muscimol diffusion up to the recording sites. Autoradiographic studies involved 25 rats and different experimental conditions. Optical density (OD) measures indicated that after a survival time of 15 min, a 0.05 microl injection produced a labeled area of 5.25 mm(2) at the injection site and a rostrocaudal labeling of 1.7 mm. Increasing the survival time to 60 min, or increasing the injected volume to 0.1 microl, systematically led to a larger labeled area at the injection site (8-12 mm(2)) and to a larger rostrocaudal diffusion (2.0-2.5 mm). Direct quantifications of radioactivity by a high-resolution radioimager validated the OD measures and even indicated a larger muscimol diffusion (up to 3.25 mm). Thus, these data point out that muscimol diffusion after intracerebral microinjection is larger than usually supposed. The relationships between these results and those obtained in behavioral studies are discussed.

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.

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.

Diversity of receptive field changes in auditory cortex during natural sleep

Twenty years ago, the study by Livingstone and Hubel [(1981) Nature, 291, 554] was viewed as a first step toward understanding how changes in state of vigilance affect sensory processing. Since then, however, very few attempts have been made to progress in this direction. In the present study, 56 cells were recorded in the auditory cortex of adult, undrugged guinea pigs, and the frequency tuning curves were tested during continuous and stable periods of wakefulness and of slow‐wave sleep (SWS). Twelve cells were also tested during paradoxical sleep. Over the whole cell population, the reponse latency, the frequency selectivity and the size of the suprathreshold receptive field were not significantly modified during SWS compared with waking. However, this lack of global effects resulted from the heterogeneity of response changes displayed by cortical cells. During SWS, the receptive field size varied as a function of the changes in evoked responses: it was unchanged for the cells whose evoked responses were not modified (38% of the cells), reduced for the cells whose responses were decreased (48%) and enlarged for the cells whose responses were increased (14%). This profile of changes differs from the prevalent receptive field shrinkage that was observed in the auditory thalamus during SWS [Edeline et al. (2000), J. Neurophysiol.,84, 934]. It also contrasts with the receptive field enlargement that was described under anaesthesia when the EEG spontaneously shifted from a desynchronized to a synchronized pattern [Wörgötter et al. (1998), Nature,396, 165]. Reasons for these differences are discussed.

Neural representations during sleep: From sensory processing to memory traces

In the course of a day, the brain undergoes large-scale changes in functional modes, from attentive wakefulness to the deepest stage of sleep. The present paper evaluates how these state changes affect the neural bases of sensory and cognitive representations. Are organized neural representations still maintained during sleep? In other words, despite the absence of conscious awareness, do neuronal signals emitted during sleep contain information and have a functional relevance? Through a critical evaluation of the animal and human literature, neural representations at different levels of integration (from the most elementary sensory level to the most cognitive one) are reviewed. Recordings of neuronal activity in animals at presentation of neutral or significant stimuli show that some analysis of the external word remains possible during sleep, allowing recognition of behaviorally relevant stimuli. Event-related brain potentials in humans confirm the preservation of some sensory integration and discriminative capacity. Behavioral and neuroimaging studies in humans substantiate the notion that memory representations are reactivated and are reorganized during post-learning sleep; these reorganisations may account for the beneficial effects of sleep on behavioral performance. Electrophysiological results showing replay of neuronal sequences in animals are presented, and their relevance as neuronal correlates of memory reactivation is discussed. The reviewed literature provides converging evidence that structured neural representations can be activated during sleep. Which reorganizations unique to sleep benefit memory representations, and to what extent the operations still efficient in processing environmental information during sleep are similar to those underlying the non-conscious, automatic processing continually at work in wakefulness, are challenging questions open to investigation.

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.

Lesions of the pedunculopontine tegmental nucleus reduce paradoxical sleep (PS) propensity: evidence from a short-term PS deprivation study in rats

Cholinergic neurons in the mesopontine tegmentum are thought to play a critical role in the generation of paradoxical sleep (PS). However, no study has yet examined whether lesions of these neurons cause deficits of PS in the rat. We describe here the effects of lesions of the pedunculopontine tegmental nucleus (PPT) on spontaneous PS and on PS propensity, expressed during and after a short period of PS deprivation. Lesions were induced by bilateral injections of ibotenate. PS deprivation was performed manually by gently waking rats each time they showed polygraphic signs of PS. Two weeks after lesions, an 8‐h baseline recording was performed; the following day, rats were PS deprived for 6u2003h and polygraphic recordings were then continued for 2u2003h, to examine recovery sleep. The same protocol was repeated 1 week later. Compared with controls and with rats with limited PPT lesions, rats bearing >u200a60% NADPH‐diaphorase‐positive cell loss within the PPT showed unaffected PS under baseline conditions. However, they made fewer attempts to enter PS during deprivation and they exhibited an attenuated rebound increase in PS time after deprivation. The number of PS attempts and the magnitude of PS rebound were negatively correlated with the percent loss of diaphorase‐positive neurons within the PPT. Thus, PS propensity that accumulated as a result of PS deprivation was reduced after extensive PPT lesions. In summary, although spontaneous PS was found to be unaltered, the PS deprivation procedure used in this study demonstrated the dysfunctioning of PS caused by PPT lesions.

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.

Induction of selective plasticity in the frequency tuning of auditory cortex and auditory thalamus neurons by locus coeruleus stimulation

Neurons in primary sensory cortices display selective receptive field plasticity in behavioral situations ranging from classical conditioning to attentional tasks, and it is generally assumed that neuromodulators promote this plasticity. Studies have shown that pairing a pure-tone and a stimulation of the nucleus basalis magnocellularis mimics the selective receptive field facilitations described after classical conditioning. Here, we evaluated the consequences of repeated pairings between a particular sound frequency and a phasic stimulation of locus coeruleus (LC) on the frequency tuning of auditory thalamus and auditory cortex neurons. Selective alterations for the paired frequency were observed for more than 30% of the cells recorded both in cortex and in thalamus. There were as much selective increases as selective decreases at the cortical level, whereas selective increases were prevailing at the thalamic level. Selective changes usually persisted 15 min after pairing in cortex; they dissipated in thalamus, and so did the general increases in both structures. In animals with stimulation sites outside the LC, pairing induced either general changes or no effect. These results indicate that the selective plasticity induced in the frequency tuning of auditory cortex neurons by LC stimulation is bidirectional, thereby suggesting that noradrenergic activation can contribute to the different forms of plasticity observed after distinct behavioral paradigms.