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GABAergic cells of the thalamic reticular nucleus (TRN) can potentially exert strong control over transmission of information through thalamus to the cerebral cortex. Anatomical studies have shown that the reticulo-thalamic connections are spatially organized in the visual, somatosensory, and auditory systems. However, the issue of how inhibitory input from TRN controls the functional properties of thalamic relay cells and whether this control follows topographic rules remains largely unknown. Here we assessed the consequences of increasing or decreasing the activity of small ensembles of TRN neurons on the receptive field properties of medial geniculate (MG) neurons. For each MG cell, the frequency tuning curve and the rate-level function were tested before, during, and after microiontophoretic applications of GABA, or of glutamate, in the auditory sector of the TRN. For 66 MG cells tested during potent pharmacological control of TRN activity, group data did not reveal any significant effects. However, for a population of 20/66 cells (all but 1 recorded in the ventral, tonotopic, division), the breadth of tuning, the frequency selectivity and the acoustic threshold were significantly modified in the directions expected from removing, or reinforcing, a dominant inhibitory input onto MG cells. Such effects occurred only when the distance between the characteristic frequency of the recorded ventral MG cell and that of the TRN cells at the ejection site was <0.25 octaves; they never occurred for larger distances. This relationship indicates that the functional interactions between TRN cells and ventral MG cells rely on precise topographic connections.

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.

In many species, neurons with highly selective stimulus-response properties characterize higher order sensory areas and/or sensory motor areas of the CNS. In the songbird nuclei, the responses of HVC (used as a proper name) neurons during playback of the bird's own song (BOS) are probably one of the most striking examples of selectivity for natural stimuli. We examined here to what extent spike-timing carries information about natural and time-reversed versions of the BOS. From a heterogenous population of 107 HVC neurons recorded in long-day or short-day conditions, a standard indicator of stimulus preference based on spike-count (the d' index) indicates that a limited proportion of cells can be classified as selective for the BOS (20% with a |d'| > 1). In contrast, quantifying the information conveyed by spike trains with the metric-space of J.D. Victor & K.P Purpura [(1996) J. Neurophysiol., 76, 1310-1326] indicates that 62% of the cells display significant amounts of transmitted information, among which 77% are 'temporal cells'. 'Temporal cells' correspond to cells transmitting significant amounts of information when spike-timing is considered, whereas no information, or lower amounts of transmitted information, is obtained when only spike-count is considered. Computing a correlation index between spike trains [S. Schreiber et al. (2003) Neurocomputing, 52-54,925-931] revealed that spike-timing reliability is higher for the forward than for the reverse BOS, whatever the day length and the cell type are. Cells classified as selective in terms of spike-counts (d' index) had greater amounts of transmitted information, but cells classified as non-selective (d' < 0.5) can also transmit significant amounts of information. Thus, information theory methods demonstrate that a much larger proportion of neurons than expected based on spike-count only participate in the discrimination between stimuli.

Although neuronal responses to species-specific vocalizations have long been described, very few between-species comparisons have been made. In a previous study, a differential representation of species-specific vocalizations was found in the auditory cortex (ACx): marmoset ACx neurons responded more, and more selectively, to marmoset calls than did cat ACx neurons [Wang, X., Kadia, S.C., 2001. Differential representation of species-specific primate vocalizations in the auditory cortices of marmoset and cat. J. Neurophysiol. 86, 2616-2620]. The present study analyzed responses of guinea-pig and rat auditory thalamus neurons to four well-defined guinea-pig vocalizations. Neurons of guinea-pigs (n = 96) and rats (n = 87) displayed similar response strength to guinea-pig vocalizations, and did not exhibit a preference for the natural over the time-reversed version of the calls in both species. This difference with the study by Wang and Kadia might suggest that, in mammals, the selectivity for the natural version of species-specific vocalizations is prominent only at the cortical level.

To what extent seasonal factors modify the neuronal functional properties within the nuclei of the avian song system remains an open question. In adult songbirds, neurons of the song premotor nucleus HVC (used as a proper name) exhibit selective responses for the bird's own song (BOS). Here we examine whether, outside the breeding season, when songs are less stereotyped, HVC neurons of male canaries still respond selectively to the BOS produced during this period. In an initial experiment, single-unit recordings (n = 114) revealed that the neuronal selectivity for the current BOS was attenuated in males exposed to a short-day photoperiod (typical of the nonbreeding season) compared with that found in males exposed to a long-day photoperiod. In long-day conditions, 35% of the cells responded to the BOS, whereas only 12% did in short-day conditions; there were four times more selective cells (d' > 1) in long-day than in short-day conditions. To determine whether these effects were the consequence of differences in acoustic features between breeding and nonbreeding songs, neurons (n = 72) recorded in short-day conditions were tested with both a short-day BOS and a long-day BOS. A low percentage of neurons exhibited responses to short-day or to long-day BOS (11% for each song). Responses of putative interneurons (spike duration < 0.4 ms) and of putative relay cells were similarly attenuated by the short-day conditions. These results strongly suggest that, in canary, rather than being a fixed property, the selectivity for the BOS moves along a continuum and peaks when the day length mimics the breeding conditions.

Neuromodulators have long been viewed as permissive factors in experience-induced cortical plasticity, both during development and in adulthood. Experiments performed over the last two decades have reported the potency of acetylcholine to promote changes in functional properties of cortical cells in the auditory, visual, and somatosensory modality. In contrast, very few attempts were made with the monoaminergic systems. The present study evaluates how repeated presentation of brief pulses of noradrenaline (NA) concomitant with presentation of a particular tone frequency changes the frequency tuning curves of auditory cortex neurons determined at 20 dB above threshold. After 100 trials of NA-tone pairing, 28% of the cells (19/67) exhibited selective tuning modifications for the frequency paired with NA. All the selective effects were obtained when the paired frequency was within 1/4 of an octave from the initial best frequency. For these cells, selective decreases were prominent (15/19 cases), and these effects lasted > or =15 min after pairing. No selective effects were observed under various control conditions: tone alone (n = 10 cells), NA alone (n = 11 cells), pairing with ascorbic acid (n = 6 cells), or with GABA (n = 20 cells). Selective effects were observed when the NA-tone pairing was performed in the presence of propranolol (4/10 cells) but not when it was performed in the presence phentolamine (0/13 cells), suggesting that the effects were mediated by alpha receptors. These results indicate that brief increases in noradrenaline concentration can trigger selective modifications in the tuning curves of cortical neurons that, in most of the cases, go in opposite direction compared with those usually reported with acetylcholine.

The neuronal selectivity observed in the avian song system for the Bird's Own Song progressively emerged as an extraordinary fruitful model to investigate the neural code underlying the recognition of complex stimuli and the occurrence of learned behaviors. In adult zebra finch, neurons from the HVC (used as a proper name) show very selective auditory responses, firing more to presentation of the Bird's Own Song (BOS) than to reverse BOS or other conspecific songs. However, as adult zebra finches always produce the same stereotyped song, the presence of such highly selective neurons in birds with larger repertoire still remains an open question. Data presented here show that neurons selective for the BOS can be found in adult canary, a seasonal breeding bird which display a large repertoire. More precisely, we found that a large proportion of neurons (29/36) exhibits higher responses to presentation of the forward than to the reverse BOS, and that 22% of the cells were identified as selective on the basis of the d' value. For a cell that was extensively studied, we evaluated to what extent temporal stimulus-related structure predicts the acoustic stimulus using linear or non-linear artificial neural networks (ANN). These analyses indicated that the temporal structure contained in spike trains characterizes more accurately the stimulus than the firing rate. The limitations of applying ANN analyses to electrophysiological data are discussed and potential solutions to increase the confidence in these analysis are proposed.

Over the last 10 years, high-frequency bursts of action potentials have been the subject of intense researches to understand their potential role in information encoding. Based on recordings from auditory thalamus neurons (n = 302) collected during anesthesia (pentobarbital, urethan, or ketamine/xylazine), waking (W), and slow-wave sleep (SWS), we investigated how bursts participate to frequency tuning, intensity-function, response latency (and latency variability), and stimulus detectability. Although present in all experimental conditions, bursts never dominated the cells mode of discharge: the highest proportion was found during ketamine/xylazine anesthesia (22%), the lowest during waking (4.5%). In all experimental conditions, bursts preferentially occurred at or around the cells best frequency (BF), thus increasing the frequency selectivity. This effect was observed at both the intensities producing the highest and the lowest evoked responses. Testing the intensity-functions indicated that for most of the cells, there was no systematic relationship between burst proportion and responses strength. Under several conditions (W, SWS, and urethan), when cells exhibited bursts >20%, the variability of their response latency was reduced in burst mode compared with single-spike mode. During W, this effect was accompanied by a reduction of the response latency. Finally, a receiver operating characteristic analysis indicated no particular relation between bursts and stimulus detectability. Compared with single-spike mode, which is present for broader frequency ranges, the prominence of bursts at the BF should contribute to filter information reaching the targets of medial geniculate cells at both cortical and subcortical levels.

Since the beginning of the 90's several lines of research have brought new insights concerning the temporal aspects of sensory processing. Initial observations showing that sensory stimuli can trigger evoked, or induced, oscillations has generated a large number of studies where, explicitly or implicitly, the large-scale rhythmic activity of thalamo-cortical neurons was viewed as a key factor to synchronize neurons responding to different dimensions of a given stimulus, and therefore to solve the so-called "binding problem" (for reviews see Eckhorn 2000, Singer 1990, 1999). This line of research contrasts with the rate coding concept which has been used over the last 40 years to describe the functional properties of neurons in sensory systems and the plasticity of sensory systems both during development and in adulthood. We review here results obtained in the thalamo-cortical auditory system. After a characterization of the oscillatory events, we determined their origins by inactivating each component of the thalamo-cortical loop. Then we compared, within the same animals, the oscillations obtained in anesthetized and unanesthetized conditions. Our data strongly suggest that to clarify the functional roles of evoked oscillations, and more generally of any aspects of temporal coding, we need to study them on awake animals.

Thalamic high frequency bursts have long been described under anesthesia and during slow-wave sleep (SWS). More recently, studies in the lateral geniculate nucleus have pointed out that they are also present during waking (W). Here, we compared the bursts recorded in the medial geniculate body of guinea pigs under anesthesia or during periods of W and SWS. The tuning of single units was tested between threshold and 80 dB SPL in two conditions: (1) in restrained, undrugged, non-sleep-deprived guinea pigs (n=101 cells) and (2) under pentobarbital anesthesia (n=53 cells). Off-line analyses allowed us to distinguish single action potentials (APs) from bursts. A burst was defined as a group of APs with an interspike interval < or =4 ms, preceded by a silent period > or =100 ms. We found that auditory thalamus bursts occur in synchronized electroencephalogram states (SWS and anesthesia), but also during W. Although the burst characteristics did not differ among the three states, group data showed that the proportion of bursts within spike trains was the greatest under anesthesia. This observation resulted from two types of effects: (1) the percentage of non-bursting cells was lowest under anesthesia and (2) some cells under anesthesia exhibited up to 90% of bursts, whereas during W or SWS the highest proportion of bursts did not exceed 40%. The presence of these bursts is discussed with regards to the known fluctuations of membrane potential which occur in these various states.

Previous anatomical experiments have demonstrated the existence of a direct, bilateral projection from the auditory cortex (AC) to the cochlear nucleus (CN). However, the precise relationship between the origin of the projection in the AC and the distribution of axon terminals in the CN is not known. Moreover, the influence of this projection on CN principal cells has not been studied before. The aim of the present study was two-fold. First, to extend the anatomical data by tracing anterogradely the distribution of cortical axons in the CN by means of restricted injections of biotinylated dextran amine (BDA) in physiologically characterized sites in the AC. Second, in an in vitro isolated whole brain preparation (IWB), to assess the effect of electrical stimulation of the AC on CN principal cells from which intracellular recordings were derived. BDA injections in the tonotopically organized primary auditory cortex and dorsocaudal auditory field at high and low best frequency (BF) sites resulted in a consistent axonal labeling in the ipsilateral CN of all injected animals. In addition, fewer labeled terminals were observed in the contralateral CN, but only in the animals subjected to injections in low BF region. The axon terminal fields consisting of boutons en passant or terminaux were found in the superficial granule cell layer and, to a smaller extent, in the three CN subdivisions. No axonal labeling was seen in the CN as result of BDA injection in the secondary auditory area (dorsocaudal belt). In the IWB, the effects of ipsilateral AC stimulation were tested in a population of 52 intracellulary recorded and stained CN principal neurons, distributed in the three CN subdivisions. Stimulation of the AC evoked slow late excitatory postsynaptic potentials (EPSPs) in only two cells located in the dorsal CN. The EPSPs were induced in a giant and a pyramidal cell at latencies of 20 ms and 33 ms, respectively, suggesting involvement of polysynaptic circuits. These findings are consistent with anatomical data showing sparse projections from the AC to the CN and indicate a limited modulatory action of the AC on CN principal cells.

The goal of this review is twofold. First, it aims to describe the dynamic regulation that constantly shapes the receptive fields (RFs) and maps in the thalamo-cortical sensory systems of undrugged animals. Second, it aims to discuss several important issues that remain unresolved at the intersection between behavioral neurosciences and sensory physiology. A first section presents the RF modulations observed when an undrugged animal spontaneously shifts from waking to slow-wave sleep or to paradoxical sleep (also called REM sleep). A second section shows that, in contrast with the general changes described in the first section, behavioral training can induce selective effects which favor the stimulus that has acquired significance during learning. A third section reviews the effects triggered by two major neuromodulators of the thalamo-cortical system--acetylcholine and noradrenaline--which are traditionally involved both in the switch of vigilance states and in learning experiences. The conclusion argues that because the receptive fields and maps of an awake animal are continuously modulated from minute to minute, learning-induced sensory plasticity can be viewed as a "crystallization" of the receptive fields and maps in one of the multiple possible states. Studying the interplays between neuromodulators can help understanding the neurobiological foundations of this dynamic regulation.

Over the last decade, exposure to high frequency (2450 MHz) electromagnetic fields (EMFs) has been found to induce performance deficit in rodents in spatial memory tasks. As concern was expressed about potential biological effects of mobile communication microwaves, studies testing the effects of signals such as GSM were required. In a previous study, using head-only exposure to 900 MHz GSM EMF, we could not demonstrate any behavioural deficit in two simple learning tasks. The present study aimed at extending these results with more complex spatial learning tasks and a non-spatial task. In a first experiment, rats were trained in a radial-arm maze with a 10-s confinement between each visited arm. In a second experiment, a 15-min intra-trial delay was introduced after four visited arms. In a third experiment, non-spatial memory was tested in an object recognition task. In all experiments, performance of the head-only exposed rats (1 and 3.5 W/kg) was compared with that of sham and control rats. In the first experiment, a slightly improved performance was found after 3.5 W/kg exposure, a result that was not observed in the delay-task. In the third experiment, although some effects on exploratory activity were found, recognition memory was unaffected in exposed rats. Altogether, this set of experiments provides no evidence indicating that spatial and non-spatial memory can be affected by a 45-min head-only exposure to 900 MHz GSM EMF.

Over the last decade, a large number of studies have characterized stimulus-evoked oscillations in the visual cortex of anesthetized and unanesthetized animals. Comparatively, only a few studies have been performed in auditory cortex. This study compared the tone-evoked oscillations detected from the same recording sites in the thalamo-cortical auditory system of unanesthetized and anesthetized rats. Simultaneous multiunit recordings were collected in auditory cortex, auditory thalamus, and the auditory sector of the reticular nucleus of restrained rats, which spontaneously shifted from waking (W) to slow-wave sleep (SWS) and paradoxical sleep (PS). Subsequently, the same recording sites were tested under pentobarbital anesthesia, then under high doses of diazepam, and finally under urethan anesthesia. Under these drugs, oscillations were detected in 54% of the recordings: one-half of them were stimulus-locked oscillations and were directly observed on peri-stimulus time histograms (PSTHs); one-half of them were non-stimulus-locked oscillations and were detected on autocorrelograms. Spontaneous oscillations were present for 17% of the recordings. During SWS, only non-stimulus-locked oscillations were observed for a small percentage of recordings (12%). This percentage did not differ significantly from the one of spontaneous oscillations obtained during SWS (8%). No oscillations were found in W and PS. Both under anesthesia and in SWS, the frequency range of the oscillations was 5-15 Hz, and there was no frequency difference between evoked and spontaneous oscillations. Although surprising, the absence of oscillations in awake animals may allow each neuron to process acoustic information independently of its neighbors and may in fact benefit auditory perception.

Since its design 25 years ago (Olton & Samuelson, 1976), the eight-arm radial maze has become very popular and is now widely used to assess spatial memory in rodents. Two versions of the full-baited maze protocol are present in the literature: with or without confinement between the visit of each arm. The confinement was introduced by Olton himself as early as 1977 (Olton, Collison, & Werz, 1977) to eliminate stereotypic behaviors that he had previously observed. It is widely regarded that the confinement prevents rodents from developing these response patterns, and as such it is considered an improved procedure to test spatial memory. Surprisingly, to the best of our knowledge, no study has been especially designed to demonstrate the efficacy of the confinement in blocking the stereotypic behaviors of the animals. The present study compares the strategies of rats trained with or without a confinement procedure. The results show that, after nine days of training, rats submitted to a 5- or a 10-s confinement reach the same level of performance as rats without confinement. The confinement totally prevents stereotypic behaviors like clockwise serial searching strategies which are often observed without confinement. Even a 0-s confinement is sufficient to prevent clockwise strategies, but rats seem to develop other stratagems which do not imply spatial memory. Furthermore, rats previously trained without confinement are unable to perform the task when confinement is introduced on a test day. In contrast, rats previously trained with confinement perform the task correctly when the confinement is no longer present. Thus, without confinement, good levels of performance can be achieved without precise spatial representations.

In songbirds, anatomical attributes of song nuclei exhibit sexual and seasonal differences. To extend these data to physiological correlates, neurons ( n= 374) were recorded in the HVc of male and female canaries during and outside the breeding period. Surprisingly, a particular type of action potential waveforms was observed more frequently in breeding than in non-breeding birds and in males than in females. These neurons showed both a shorter action potential duration (< 0.4 ms) and a higher firing rate (2.5 1.4 spikes/s) than the other neurons. Such characteristics are usually associated with interneurons in the songbird HVc as well as in the mammalian neocortex. Thus, these results provide the first electrophysiological evidence for an alteration of the neuronal network of HVc across sexes and seasons.

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., (Copyright 2002 Elsevier Science (USA).)

The rapid expansion of mobile communication has generated intense interest, but has also fuelled ongoing concerns. In both humans and animals, radiofrequency radiations are suspected to affect cognitive functions. More specifically, several studies performed in rodents have suggested that spatial learning can be impaired by electromagnetic field exposure. However, none of these previous studies have simulated the common conditions of GSM mobile phones use. This study is the first using a head-only exposure system emitting a 900-MHz GSM electromagnetic field (pulsed at 217 Hz). The two behavioural tasks that were evaluated here have been used previously to demonstrate performance deficits in spatial learning after electromagnetic field exposure: a classical radial maze elimination task and a spatial navigation task in an open-field arena (dry-land version of the Morris water maze). The performances of rats exposed for 45 min to a 900-MHz electromagnetic field (1 and 3.5 W/kg) were compared to those of sham-exposed and cage-control rats. There were no differences among exposed, sham, and cage-control rats in the two spatial learning tasks. The discussion focuses on the potential reasons that led previous studies to conclude that learning deficits do occur after electromagnetic field exposure.

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 response 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.

Based on neuronal recordings in the HVc, this study investigated differences between reproductively active male and sexually receptive female canaries. It is the first study to describe auditory responses and cell characteristics of HVc neurons in female songbirds and to compare them with the responses and characteristics obtained in males. Extracellular single unit recordings showed that in males HVc cells exhibited two types of auditory responses to conspecific and heterospecific song playbacks: tonic and phasic responses. The major finding of the present study is the absence of tonic responses in females. Neurons in the HVc of females only responded phasically to song playbacks. In both sexes, neurons exhibiting auditory responses had thinner action potentials than the others. As all the tonic cells recorded in males were thin spike cells (action potential < or = 0.6 ms) [corrected] and had high firing rates (6 Hz in average), they are potentially interneurons. In both sexes, two categories of nonresponsive cells were found: neurons that did not fire at song onset and had the lowest spontaneous firing rate; and neurons that did not exhibit changes in activity in response to song playbacks. Analyses of physiological characteristics of HVc neurons revealed that the rate of spontaneous activity was higher in males than in females. This study is a first step towards identifying [corrected] the cellular bases of the sexual dimorphism in HVc function and highlights the pivotal role of interneurons in HVc auditory processing.

This study investigates the origins of tone-evoked oscillations (5-13 Hz) in the thalamo-cortical auditory system of anaesthetized rats. In three separate experiments, the auditory sector of the reticular nucleus (RE), the auditory cortex and the auditory thalamus were inactivated by local applications of muscimol (1 mg/mL). To assess the efficacy of this procedure, recordings were performed in the inactivated structure in each experiment; and to determine the extent of the drug diffusion autoradiographic experiments were carried out. The evolution of the strength of the oscillations was followed using power spectra during the whole recording session. In the first experiment, muscimol injection in the auditory RE totally suppressed the tone-evoked oscillations in the auditory thalamus and cortex. In the second experiment, inactivation of the auditory cortex did not interfere with the presence of tone-evoked oscillations in the auditory RE. In the third experiment, inactivation of the auditory thalamus impaired the oscillations produced by cortical stimulation in the auditory RE. From these results, it appears that both the auditory thalamus and the auditory sector of the RE, but not the auditory cortex, are involved in the generation of stimulus-evoked oscillations in the thalamo-cortical auditory system.

The present study describes how the frequency receptive fields (RF) of auditory thalamus neurons are modified when the state of vigilance of an unanesthetized animal naturally fluctuates among wakefulness (W), slow-wave sleep (SWS), and paradoxical sleep (PS). Systematic quantification of several RF parameters-including strength of the evoked responses, response latency, acoustic threshold, shape of rate-level function, frequency selectivity, and RF size-was performed while undrugged, restrained guinea pigs presented spontaneous alternances of W, SWS, and PS. Data are from 102 cells recorded during W and SWS and from 53 cells recorded during W, SWS, and PS. During SWS, thalamic cells behaved as an homogeneous population: as compared with W, most of them (97/102 cells) exhibited decreased evoked spike rates. The frequency selectivity was enhanced and the RF size was reduced. In contrast during PS, two populations of cells were identified: one (32/53 cells) showed the same pattern of changes as during SWS, whereas the other (21/53 cells) expressed values of evoked spike rates and RF properties that did not significantly differ from those in W. These two populations were equally distributed in the different anatomical divisions of the auditory thalamus. Last, during both SWS and PS, the responses latency was longer and the acoustic threshold was higher than in W but the proportion of monotonic versus nonmonotonic rate-level functions was unchanged. During both SWS and PS, no relationship was found between the changes in burst percentage and the changes of the RF properties. These results point out the dual aspect of sensory processing during sleep. On the one hand, they show that the auditory messages sent by thalamic cells to cortical neurons are reduced both in terms of firing rate at a given frequency and in terms of frequency range. On the other hand, the fact that the frequency selectivity and the rate-level function are preserved suggests that the messages sent to cortical cells are not deprived of informative content, and that the analysis of complex acoustic sounds should remain possible. This can explain why, although attenuated, reactivity to biologically relevant stimuli is possible during sleep.

Tone-evoked oscillations were studied from simultaneous recordings collected in the auditory cortex, auditory thalamus and auditory sector of the reticular nucleus in urethane anesthetized rats. These oscillations were precisely time-locked to tone onset and were easily observed on peristimulus time histograms (PSTHs). Visual inspection of PSTHs and rasters led us to distinguish between 'reliable' oscillations (which exhibited oscillatory patterns in more than 50% of the trials) and 'labile' oscillations (which exhibited oscillations in less than 50% of the trials). Systematic quantification of oscillations based on several indices derived from power spectra confirmed this distinction. 'Reliable' stimulus-locked oscillations were observed in 51/184 (28%) of the recordings from auditory cortex, 9/55 (17%) of the recordings from auditory thalamus and 11/26 (42%) of the recordings from the auditory sector of the reticular nucleus. The frequency range of these oscillations was the same in the three structures (5-14 Hz). Within the same animal, when one electrode exhibited oscillations, there was a high probability of detecting similar oscillations from electrodes located in the same structure, but not from electrodes located in the other structures. These oscillations were observed for pure tone frequency (or for clicks) whatever the tone duration (1 s, 100 ms, 10 ms). The inter-tone interval (ITI) was found to be the critical factor controlling the occurrence of these oscillations: they were present for ITIs of 2 s or longer, but were absent for ITIs of 1 s or less. In contrast, the occurrence of the oscillations was a function neither of the strength of the 'on' evoked response nor of the animal's temperature. However, lowering the animal's temperature from 37-38 degrees C to 35-36 degrees C systematically led to a decrease in the frequency and an increase in the duration of the tone-evoked oscillations. These results suggest that, even in well defined conditions (temperature, EEG, ITI, level of anesthesia), the oscillations triggered by presentation of the same stimulus can be stable or unstable. This temporal instability of stimulus-evoked oscillations has to be taken into account before stating percentages of oscillations in a given brain structure. They also suggest that some general factors such as the animals temperature or the inter-stimulus interval can considerably affect their characteristics and/or their occurrence.

The mode of discharge of auditory cortex cells was studied during iontophoretic application of noradrenaline (NA). Only seven of 190 cells showed changes in interspike interval distribution during NA application. A similar conclusion was drawn when the analysis focused on 68 cells classified as bursting (n = 15), regular spiking (n = 49) or thin spike (n = 4) cells. Only two bursting cells showed changes in their ISI distribution. The effects on the mode of discharge were independent of the effect on the spike rate and were not a function of cortical depth. These results suggest that the changes in firing mode previously described in vitro occur for a limited percentage of cells and/or for cell types not very often recorded in vivo.

This study shows the effects of noradrenaline (NA) on receptive fields of auditory cortex neurons in awake animals; it is the first one to describe the effects of NA on neurons in sensory cortex, in different natural states of vigilance. The frequency receptive field of 250 auditory cortex neurons was determined before, during and after ionophoretic application of NA while recording the state of vigilance of unanaesthetized guinea-pigs. When NA significantly changed the spontaneous activity (85 out of 250 cells), the dominant effect was a decrease (61 out of 85 cells, 72%). When NA significantly changed the evoked activity (107 out of 250 cells), the dominant effect was also a decrease (84 out of 107 cells, 78%). During and after NA application, the signal-to-noise ratio (S/N, i.e. evoked/spontaneous activity) was unchanged, but the selectivity for pure-tone frequencies was enhanced. When the effects occurring in wakefulness and in slow-wave sleep (SWS) were compared, it appeared that the predominantly inhibitory effect of NA on spontaneous and evoked activity was present in both states. The S/N ratio was unchanged and the selectivity was increased in both states. However, during SWS, the percentage of cells inhibited by NA was lower, and the effects on the frequency selectivity were smaller than in wakefulness. In contrast, GABA produced similar inhibitory effects on spontaneous and on evoked activity during wakefulness and SWS. Comparisons with previous data obtained using the same protocol in urethane anaesthetized animals (Manunta & Edeline 1997) indicate that the effects of NA were qualitatively the same. Based on these results, we suggest that any hypothesis concerning the role of NA in cortical plasticity should take into account the fact that the predominantly inhibitory effects of NA lead to decrease the size of the receptive field.

Previous studies performed in anesthetized animals have shown differences between the acoustic responses of neurons recorded from the different divisions of the medial geniculate body (MGB). This study aimed at determining whether or not such differences are also expressed when neurons are recorded from awake animals. The auditory responses of 130 neurons of the auditory thalamus were determined in awake, restrained guinea pigs while the state of vigilance of the animals was continuously monitored. There were significantly more 'on' phasic evoked responses and significantly fewer 'non-responsive' or 'labile' cells in the ventral division of the MGB (MGv) than in the other divisions. The response latencies and the variability of the latencies were smaller in the MGv than in the other divisions. The tuning of the neurons obtained from MGv and from the lateral part of the posterior complex were significantly sharper than those coming from the dorsal division of the MGB and the medial division. The mean threshold and the percentage of monotonic vs. non-monotonic intensity functions were not different in the subdivisions of the auditory thalamus. When compared with previous studies, the quantifications of the acoustic responses obtained in the present study gave values that differed from those reported under deep anesthesia, but were close to those reported under light anesthesia. Lastly, even if none of the physiological characteristic makes it possible, by itself, to determine the locus of recordings in the auditory thalamus, we conclude that the physiological characteristics of the evoked responses obtained in MGv differ from those of other divisions.

The goal of this review is to give a detailed description of the main results obtained in the field of learning-induced plasticity. The review is focused on receptive field and map changes observed in the auditory, somatosensory and visual thalamo-cortical system as a result of an associative training performed in waking animals. Receptive field (RF) plasticity, 2DG and map changes obtained in the auditory and somatosensory system are reviewed. In the visual system, as there is no RF and map analysis during learning per se, the evidence presented are from increased neuronal responsiveness, and from the effects of perceptual learning in human and non human primates. Across sensory modalities, the re-tuning of neurons to a significant stimulus or map reorganizations in favour of the significant stimuli were observed at the thalamic and/or cortical level. The analysis of the literature in each sensory modality indicates that relationships between learning-induced sensory plasticity and behavioural performance can, or cannot, be found depending on the tasks that were used. The involvement (i) of Hebbian synaptic plasticity in the described neuronal changes and (ii) of neuromodulators as "gating" factors of the neuronal changes, is evaluated. The weakness of the Hebbian schema to explain learning-induced changes and the need to better define what the word "learning" means are stressed. It is suggested that future research should focus on the dynamic of information processing in sensory systems, and the concept of "effective connectivity" should be useful in that matter.

To test a potential "gating" effect of noradrenaline (NA) in the auditory cortex, the acoustic threshold was estimated by determining the rate-level function of neurons before, during, and after microiontophoretic application (5-40 nA) of NA. The rationale behind this experiment was that a gating effect should decrease the threshold for acoustic excitatory responses. From 84 recorded neurons, we observed (1) that application of NA increased the threshold for 48 of 84 cells, and (2) that, on average, the slope of the rate-level functions was unchanged. These effects on the threshold are consistent with the fact that the dominant effect of NA on the evoked response is inhibition for 34 of 84 cells; increases in evoked responses were observed for only 14 of 84 cells. GABA application (0-50 nA) also led to increased response threshold for 19 of 24 cells (unaffected, 5 of 24 cells). However, for three cells the effect of GABA application was antagonized by bicuculline application, while on the same cells bicuculline application did not prevent the noradrenergic increase in threshold. The effect induced by NA on the threshold raises questions about the generality of a gating effect of NA in sensory neocortex.

The selectivity of rat auditory cortex neurons for pure tone frequency was studied during and after ionophoretic application (5-40 nA) of noradrenaline in urethane-anaesthetized rats. The dominant effect induced by noradrenaline was a significant decrease in spontaneous (93/268 cells) and evoked activity (133/268 cells) which outlasted the application. In the whole population of cells (n = 268) the signal-to-noise ratio, computed using as the signal either the mean evoked response or the response at the best frequency, was unchanged during noradrenaline application. It was significantly increased only for cells showing significantly decreased spontaneous activity, and was significantly decreased for cells showing increased spontaneous activity. Frequency selectivity was significantly increased for the whole population during and after noradrenaline application. It was also significantly increased for cells showing significantly decreased evoked activity, and was significantly decreased for cells showing increased evoked activity. The noradrenaline-induced inhibition was not blocked by propranolol (beta antagonist); it was blocked by prazosin (alpha1 antagonist) and partly mimicked by phenylephrine (alpha1 agonist). GABA, which also inhibited spontaneous and evoked activity, slightly increased the signal-to-noise ratio and significant increased frequency selectivity. However, when noradrenaline was ejected in the presence of bicuculline at doses that were able to block GABAergic inhibition, the inhibitory effects of noradrenaline on spontaneous and evoked activity were still observed. The possible function of noradrenaline-induced inhibitions in sensory cortices is briefly discussed.

Idazoxan (IDA), an alpha 2 antagonist of adrenoceptors, has been shown to increase cortical release of norepinephrine (NE) by an action mediated primarily by the alpha 2 autoreceptors located on the NE terminals. In the present experiment, IDA application was used to increase the cortial concentration of NE. Single unit activity (n = 107) was recorded in the rat auditory cortex, and the neurons' frequency receptive fields (FRF) were determined before and after systemic (intraperitoneal or intravenous) or local application of IDA. In the whole population (n = 107) there was a decrease in spontaneous activity and/or evoked activity for 84% of the recordings (90/107 cells). Decreased tone-evoked responses were obtained after systemic injections (n = 39), as well as after local applications (n = 68) of IDA. These effects were not observed after either systemic injections (n = 13) or local applications (n = 9) of saline. The signal-to-noise ratio (the mean evoked responses divided by the spontaneous activity) was slightly decreased after systemic injections and slightly increased after local applications. However, after both systemic and local injections the frequency selectivity of the neuronal responses was increased. For a group of neurons (n = 27), testing the FRF at three intensities indicated that this increased selectivity can be expressed at high or middle range intensity but not at low intensity. For 37 cells, the intensity function was tested at the best frequency before and after IDA application, and the threshold for excitatory responses was determined in 28 cases. An increased threshold was observed in 16 of 28 cases after IDA application. Thus, using a pharmacological procedure to increase the extracellular concentration of NE, the dominant inhibitory effect on the auditory cortex neurons led to an enhancement of the frequency selectivity, but also an increase in the threshold of these neurons.

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.

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.

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.

Classical conditioning induces frequency-specific receptive field (RF) plasticity in the auditory cortex after relatively brief training (30 trials), characterized by increased response to the frequency of the conditioned stimulus (CS) and decreased responses to other frequencies, including the pretraining best frequency (BF). This experiment determined the development of this CS-specific RF plasticity. Guinea pigs underwent classical conditioning to a tonal frequency, and receptive fields of neurons in the auditory cortex were determined before and after 5, 15, and 30 CS-US (unconditioned stimulus) pairings, as well as 1 hr posttraining. Highly selective RF changes were observed as early as the first 5 training trials. They culminated after 15 trials, then stabilized after 30 trials and 1 hr posttraining. The rapid development of RF plasticity satisfies a criterion for its involvement in the neural bases of a specific associative memory.

Classical conditioning is known to induce frequency-specific receptive field (RF) plasticity in the auditory cortex (ACx). This study determined the effects of discrimination training on RFs at two levels of task difficulty. Single unit and cluster discharges were recorded in the ACx of adult guinea pigs trained in a tone-shock frequency discrimination paradigm (30 intermixed trials each of positive conditioned stimulus [CS+]-shock and negative CS [CS-] alone) with behavioral performance indexed by the cardiac deceleration conditioned response (CR). After training in an easy task in which subjects developed discriminative CRs, they were trained in a difficult task (reduced frequency distance between CS+ and CS-) in which they failed to discriminate. However, frequency-specific RF plasticity developed at both levels of task difficulty. Responses to the frequency of the CS+ were increased, whereas responses to other frequencies, including the CS- and the prepotent best frequency (BF) were reduced. In many cases, tuning was shifted such that the frequency of the CS+ became the new BF. The effects were present or stronger after a 1-hr retention interval. The role of RF plasticity in the ACx is discussed for behavioral performance and information storage.

The medial division of the medial geniculate nucleus (MGm) and the posterior intralaminar nucleus (PIN) are necessary for fear conditioning to an auditory conditioned stimulus (CS), receive both auditory and somatosensory input, and project to the amygdala, which is involved in production of fear conditioned responses. If CS-unconditioned stimulus (US) convergence in the MGm-PIN is critical for fear conditioning, then microstimulation of this area should serve as an effective US during classical conditioning, in place of standard footshock. Guinea pigs underwent conditioning (40-60 trials) using a tone as the CS and medial geniculate complex microstimulation as the US. Conditioned bradycardia developed when the US electrodes were in the PIN. However, microstimulation was not an effective US for conditioning in other parts of the medial geniculate or for sensitization training in the PIN or elsewhere. Learning curves were similar to those found previously for footshock US. Thus, the PIN can be a locus of functional CS-US convergence for previously for footshock US. Thus, the PIN can be a locus of functional CS-US convergence for fear conditioning to acoustic stimuli.

The medial division of the medial geniculate body (MGm) projects to the lateral amygdala and the upper layer of auditory cortex and develops physiological plasticity rapidly during classical conditioning. The effects of learning on frequency receptive fields (RFs) in the MGm of the guinea pig have been determined. Classical conditioning (tone-footshock), as indexed by rapid development of conditioned bradycardia, produced conditioned stimulus (CS)-frequency specific RF plasticity: increased response at the CS frequency with decreased responses at other frequencies, both immediately and after a 1-hr retention period. Sensitization training produced only general changes in RFs. These findings are considered with reference to both the elicitation of amygdala-mediated, fear-conditioned responses and the mechanism of retrieval of information stored in the auditory cortex during acquisition.

The effects of classical conditioning on frequency receptive fields (RFs) in the ventral, tonotopic part of the guinea pig (Cavia porcellus) medial geniculate ventral body (MGv) during cardiac conditioning to a single tone frequency were studied. Associative frequency-specific plasticity, in which the RF was returned to the frequency of the conditioned stimulus (CS), developed if the CS frequency was within 0.125 octave of the pretraining best frequency. Otherwise, a general increase across the RF developed. Sensitization training also produced general increased responses. The frequency-specific plasticity was short-term and observed only immediately after training, whereas the general effects were maintained. These results suggest that frequency-specific RF plasticity in the MGv may be a substrate of short-term mnemonic processes that could participate in long-term storage of information and modification of the representation of the CS at the auditory cortex.

Multiunit activity (MUA) was chronically recorded in the hippocampal CA3 field of rats using a blocking paradigm with conditioned suppression of lever pressing for food as the measure of conditioning. In Experiment 1, a classical blocking paradigm demonstrated the good conditionability of 2 stimuli (a light and a tone) and their respective ability to block each other. In Experiment 2, MUA was recorded in CA3 cells in rats submitted to a similar paradigm. Four groups received either tone (groups B and B1) or click (groups BC and B1C) conditioned stimulus (CS) presentations that were followed immediately by an electrical footshock (unconditioned stimulus, US). The rats were then given either 40 (groups B and BC) or 1 (groups B1 and B1C) tone + light-footshock presentations. During test sessions, the animals showed MUA responses to the added CS (light), with no conditioned suppression of lever presses occurring during CS presentations. The results of Experiment 3 strongly suggest that hippocampal increase in cellular activity to the light appeared at the first compound trial presentation. Conditioning to the light obtained by increasing the US intensity after the single compound trial suggests that the hippocampal response reflects a redundant CS-US association (light-shock). Long-term retention tests given 45 days after the end of conditioning revealed that behavioral and hippocampal responses could still be detected but only in response to the stimulus that had elicited a behavioral response during learning.

Highly specific subcortical receptive field (RF) plasticity was found in the dorsal division of the guinea pig medial geniculate body during cardiac conditioning to a tonal frequency. There was increased response to the conditioned-stimulus (CS) frequency, and there were decreased responses to adjacent frequencies, especially at the pretraining best frequency (BF), which often resulted in a shift of tuning such that the CS became the new BF. Moreover, 1 hr later the effects were stronger, more sharply tuned, and centered on the CS frequency. A sensitization paradigm produced only broad, general increases of response across the RF. These findings reveal that the analysis of sensory RF dynamics is a valuable approach to understanding the neural mechanisms of information processing in learning and memory.

The effects of conditioning (tone-footshock pairing) on single unit discharges in the magnocellular medial geniculate (mMG) were examined in rats submitted to pairing under ketamine. For all the semichronic animals, the conditioned suppression of lever pressing for food observed subsequently indicated that at the behavioral level, an acquisition takes place during the pairing. The activity of 37 single unit activities was recorded both during pairing and during determination of frequency-selectivity before and after pairing. The results showed that 54% (20/37) of the cells exhibited plasticity of their evoked response (increase or decrease) during pairing compared with the habituation or the sensitization phase. Moreover, 75% of these changes (15/20 cells) were specific for the frequency used as conditioned stimulus during conditioning. Modifications of background activity were observed during pairing or sensitization and were never correlated with modifications of the evoked responses. These results suggest that specific modifications of the frequency receptive field of the mMG cells occur during acquisition of classical conditioning.

Multiunit activity was chronically recorded in the hippocampus (CA3 field), the magnocellular medial geniculate (MGm) and the auditory cortex (AC) of rats during acquisition (12 daily sessions, 10 trials per session) and long-term retention of differential classical conditioning (tones paired with footshocks). Marked increases of multiunit discharges to CS + presentations were first detected in the MGm (5-10 trials) followed (10-20 trials) by the emergence of discriminative responses in the hippocampus and in the AC. During long-term retention tests, 45 days after the end of conditioning, CS + selective responses were observed in the 3 structures. We propose that learning-induced changes in the conditioned stimulus (CS) sensory pathway can have the same temporal stability as the sensory plasticity observed during development or post injury in adult animals.

Multiunit activity (MUA) was recorded chronically in the hippocampus (CA3) and the medial geniculate body (mMG) during habituation to a tone followed by conditioning (tone paired with footshock) or pseudoconditioning (tone/footshock unpaired) in rats previously trained in a lever-pressing for food task (VI 60). In the conditioned group pairing tones with footshocks rapidly induced an increase in the initial CS-evoked response in the mMG, followed by the emergence of a hippocampal response and a marked conditioned suppression of lever-pressing to the tone. In contrast, in the pseudoconditioned group, the stimulus induced only transient cellular changes in the hippocampus and in the mMG, while no behavioral suppression to the tone could be seen. Moreover, presentations of the CS 45 days later induced multiunit and behavioral responses in both structures, only in the conditioned group. These results are used for discussion of the role of learning-induced changes in the sensory structure (mMG) as compared with changes in an associative structure (hippocampus), during acquisition and retention of a conditioned response.

Multiunit activity was recorded in the CA3 field of the dorsal hippocampus in freely moving rats during classical conditioning and subsequent presentation of the CS on operant baselines for food reward as well as shock avoidance. Rats were first trained in a nonsignaled bar-pressing-dependent shock omission task and in a food-motivated lever-pressing task (60-s VI). Five sessions with presentations of a previously habituated tone as a CS paired with footshock as a US were then given. Testing was carried out by presenting the CS alone while behavioral responses were maintained by reinforcement in both instrumental tasks on alternate sessions. As expected, the CS induced a marked suppression of lever pressing for food reward and a marked enhancement of bar-pressing for shock avoidance. The analysis of the frequency of multiunit discharges to the CS revealed that the hippocampal cellular responses established during classical conditioning were maintained while two different behavioral responses were exhibited to the CS. The results showed that the associative response of hippocampal neurons may be dissociated from the Pavlovian conditioned responses the CS elicits. They support the hypothesis that hippocampal cellular responses represent a neural index of the acquired CS-US associative representation.

In order to assess learning possibilities under ketamine anesthesia, rats underwent a pavlovian conditioning (tone paired with foot-shock), and were subsequently tested in a conditioned suppression of lever pressing for food paradigm. First, two sessions of 70 trials were conducted, on 4 groups of anesthetized rats: a conditioned group (group C) experienced the tone (CS+) always paired with foot-shocks, whereas a discriminative group (group D) was submitted to a differential conditioning (CS+ followed by the US and a CS- always presented alone). Another group (habituated, H) received presentations of tone (CS+) alone and the fourth group (naive animals, N) was never anesthetized. Seven days later, while rats were pressing the lever to get food, CS+ presentations elicited a significant conditioned suppression of instrumental responses only in groups C and D. Moreover, a differential effect between CS+ and CS- was obtained for group D. These results indicate that a Pavlovian conditioning can occur under anesthesia, and then that its memory can last at least 7 days. The particular specific effects of ketamine are discussed to account for these results.