Jean-Marc Edeline

Rapid development of learning-induced receptive field plasticity in the auditory cortex.

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.

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.

Thalamic short-term plasticity in the auditory system: Associative retuning of receptive fields in the ventral medial geniculate body.

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.

Effects of Noradrenaline on Frequency Tuning of Rat Auditory Cortex Neurons

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 (1331268 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 (β antagonist); it was blocked by prazosin (α1 antagonist) and partly mimicked by phenylephrine (α1 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.

Head-only exposure to GSM 900-MHz electromagnetic fields does not alter rat’s memory in spatial and non-spatial tasks

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.

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.

A Spike-Timing Code for Discriminating Conspecific Vocalizations in the Thalamocortical System of Anesthetized and Awake Guinea Pigs

Understanding how communication sounds are processed and encoded in the central auditory system is critical to understanding the neural bases of acoustic communication. Here, we examined neuronal representations of species-specific vocalizations, which are communication sounds that many species rely on for survival and social interaction. In some species, the evoked responses of auditory cortex neurons are stronger in response to natural conspecific vocalizations than to their time-reversed, spectrally identical, counterparts. We applied information theory-based analyses to single-unit spike trains collected in the auditory cortex (n = 139) and auditory thalamus (n = 135) of anesthetized animals as well as in the auditory cortex (n = 119) of awake guinea pigs during presentation of four conspecific vocalizations. Few thalamic and cortical cells (<10%) displayed a firing rate preference for the natural version of these vocalizations. In contrast, when the information transmitted by the spike trains was quantified with a temporal precision of 10–50 ms, many cells (>75%) displayed a significant amount of information (i.e., >2SD above chance levels), especially in the awake condition. The computed correlation index between spike trains (Rcorr, defined by Schreiber et al., 2003) indicated similar spike-timing reliability for both the natural and time-reversed versions of each vocalization, but higher reliability for awake animals compared with anesthetized animals. Based on temporal discharge patterns, even cells that were only weakly responsive to vocalizations displayed a significant level of information. These findings emphasize the importance of temporal discharge patterns as a coding mechanism for natural communication sounds, particularly in awake animals.

Effects of noradrenaline on frequency tuning of auditory cortex neurons during wakefulness and slow‐wave sleep

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.

Does head-only exposure to GSM-900 electromagnetic fields affect the performance of rats in spatial learning tasks?

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.