Asymmetric pulses delivered by a cochlear implant allow a reduction in evoked firing rate and in spatial activation in the guinea pig auditory cortex.

Despite that fact that the cochlear implant (CI) is one of the most successful neuro-prosthetic devices which allows hearing restoration, several aspects still need to be improved. Interactions between stimulating electrodes through current spread occurring within the cochlea drastically limit the number of discriminable frequency channels and thus can ultimately result in poor speech perception. One potential solution relies on the use of new pulse shapes, such as asymmetric pulses, which can potentially reduce the current spread within the cochlea. The present study characterized the impact of changing electrical pulse shapes from the standard biphasic symmetric to the asymmetrical shape by quantifying the evoked firing rate and the spatial activation in the guinea pig primary auditory cortex (A1). At a fixed charge, the firing rate and the spatial activation in A1 decreased by 15 to 25 % when asymmetric pulses were used to activate the auditory nerve fibers, suggesting a potential reduction of the spread of excitation inside the cochlea. A strong "polarity-order" effect was found as the reduction was more pronounced when the first phase of the pulse was cathodic with high amplitude. These results suggest that the use of asymmetrical pulse shapes in clinical settings can potentially reduce the channel interactions in CI users.

Robustness to Noise in the Auditory System: A Distributed and Predictable Property.

Background noise strongly penalizes auditory perception of speech in humans or vocalizations in animals. Despite this, auditory neurons are still able to detect communications sounds against considerable levels of background noise. We collected neuronal recordings in cochlear nucleus (CN), inferior colliculus (IC), auditory thalamus, and primary and secondary auditory cortex in response to vocalizations presented either against a stationary or a chorus noise in anesthetized guinea pigs at three signal-to-noise ratios (SNRs; -10, 0, and 10 dB). We provide evidence that, at each level of the auditory system, five behaviors in noise exist within a continuum, from neurons with high-fidelity representations of the signal, mostly found in IC and thalamus, to neurons with high-fidelity representations of the noise, mostly found in CN for the stationary noise and in similar proportions in each structure for the chorus noise. The two cortical areas displayed fewer robust responses than the IC and thalamus. Furthermore, between 21% and 72% of the neurons (depending on the structure) switch categories from one background noise to another, even if the initial assignment of these neurons to a category was confirmed by a severe bootstrap procedure. Importantly, supervised learning pointed out that assigning a recording to one of the five categories can be predicted up to a maximum of 70% based on both the response to signal alone and noise alone.

Age-related Changes in Auditory Cortex Without Detectable Peripheral Alterations: A Multi-level Study in Sprague-Dawley Rats.

Aging is often considered to affect both the peripheral (i.e. the cochlea) and central (brainstem and thalamus-cortex) auditory systems. We investigated the effects of aging on the cochlea, brainstem and cortex of female Sprague-Dawley rats. The auditory nerve threshold remained stable between the ages of nine and 21 months, as did distortion product otoacoustic emissions and the number of ribbon synapses between inner hair cells and nerve fibers. The first clear signs of aging appeared in the brainstem, in which response amplitude decreased, with thresholds remaining stable until the age of 15 months, and increasing slightly thereafter. The responses of primary auditory cortex neurons revealed specific effects of aging: at 21 months, receptive fields were spectrally narrower and the temporal reliability of responses to communication sounds was lower. However, aging had a null or even positive effect on neuronal responses in the presence of background noise, responses to amplitude-modulated sounds, and responses in gap-detection protocols. Overall, inter-animal variability remained high relative to the variability across groups of different ages, for all parameters tested. Behavioral performance for the modulation depth of amplitude modulation noise was worse in 21-month old animals than in other animals. Age-related alterations of cortical and behavioral responses were thus observed in animals displaying no signs of aging at the peripheral level. These results suggest that intrinsic, central aging effects can affect the perception of acoustic stimuli independently of the effects of aging on peripheral receptors.

A Neural Substrate for Rapid Timbre Recognition? Neural and Behavioral Discrimination of Very Brief Acoustic Vowels.

The timbre of a sound plays an important role in our ability to discriminate between behaviorally relevant auditory categories, such as different vowels in speech. Here, we investigated, in the primary auditory cortex (A1) of anesthetized guinea pigs, the neural representation of vowels with impoverished timbre cues. Five different vowels were presented with durations ranging from 2 to 128 ms. A psychophysical experiment involving human listeners showed that identification performance was near ceiling for the longer durations and degraded close to chance level for the shortest durations. This was likely due to spectral splatter, which reduced the contrast between the spectral profiles of the vowels at short durations. Effects of vowel duration on cortical responses were well predicted by the linear frequency responses of A1 neurons. Using mutual information, we found that auditory cortical neurons in the guinea pig could be used to reliably identify several vowels for all durations. Information carried by each cortical site was low on average, but the population code was accurate even for durations where human behavioral performance was poor. These results suggest that a place population code is available at the level of A1 to encode spectral profile cues for even very short sounds.

Auditory thalamus responses to guinea-pig vocalizations: a comparison between rat and guinea-pig.

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.

Auditory thalamus bursts in anesthetized and non-anesthetized states: contribution to functional properties.

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.

The projection from auditory cortex to cochlear nucleus in guinea pigs: an in vivo anatomical and in vitro electrophysiological study.

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.

Differences in auditory and physiological properties of HVc neurons between reproductively active male and female canaries (Serinus canaria).

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.

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 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.

Tone-evoked oscillations in the rat auditory cortex result from interactions between the thalamus and reticular nucleus.

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.

Auditory thalamus neurons during sleep: changes in frequency selectivity, threshold, and receptive field size.

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.

Characteristics of reliable tone-evoked oscillations in the rat thalamo-cortical auditory system.

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.

Noradrenaline does not change the mode of discharge of auditory cortex neurons.

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.

Do auditory responses recorded from awake animals reflect the anatomical parcellation of the auditory thalamus?

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.

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.

Learning-induced physiological plasticity in the thalamo-cortical sensory systems: a critical evaluation of receptive field plasticity, map changes and their potential mechanisms.

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.

Effects of noradrenaline on rate-level function of auditory cortex neurons: is there a "gating" effect of noradrenaline?

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.

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 (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.

Does Hebbian synaptic plasticity explain learning-induced sensory plasticity in adult mammals?

Over the last decade, a large number of studies have demonstrated that sensory systems undergo functional reorganizations in adult mammals. In the auditory system, highly specific reorganizations were observed during learning situations in which a particular tone frequency predicts the occurrence of an aversive event. After a brief overview of the specific receptive field changes observed after associative learning in cortical and thalamic neurons, I will raise the question concerning whether or not Hebbian synaptic plasticity adequately accounts for these data. The required conditions for Hebbian synaptic plasticity to act do not seem to be met in situations in which learning-induced receptive field plasticity occurs. This analysis points out the weakness of the traditional Hebbian scheme to provide realistic bases for learning-induced neuronal plasticity and stresses the need to look for other potential mechanisms involving neuromodulators.

The alpha 2-adrenergic antagonist idazoxan enhances the frequency selectivity and increases the threshold of auditory cortex neurons.

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.