Effects of neropinephrine 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

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

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

Auditory Thalamus Neurons During Sleep: Changes in Frequency Selectivity, Threshold, and Receptive Field Size

International audience. 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 slee

Diversity of receptive field changes in auditory cortex during natural sleep

International audienceTwenty years ago, the study by Livingstone and Hubel [(1981) Nature, 291, 554] was viewed as a ®rst 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 ®eld were not signi®cantly modi®ed 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 ®eld size varied as a function of the changes in evoked responses: it was unchanged for the cells whose evoked responses were not modi®ed (38% of the cells), reduced for the cells whose responses were decreased (48%) and enlarged for the cells whose responses were increased (14%). This pro®le of changes differs from the prevalent receptive ®eld shrinkage that was observed in the auditory thalamus during SWS [Edeline et al. (2000), J. Neurophysiol., 84, 934]. It also contrasts with the receptive ®eld enlargement that was described under anaesthesia when the EEG spontaneously shifted from a desynchronized to a synchronized pattern [Worgotter et al. (1998), Nature, 396, 165]. Reasons for these differences are discussed

Chronic hepatic cytolysis revealing a pheochromocytoma.

International audienceWe report here the first case of chronic cytolysis that led to the diagnosis of pheochromocytoma, in a 48-year-old woman with a recent onset of hypertension. The etiological research ruled out the common causes of raised transaminase levels, and led to the discovery of a left adrenal pheochromocytoma. The sustained normalization of liver function tests after the removal of the tumour strongly suggests that hepatocyte injury was due to catecholamine hyperproduction. The present original clinical case, linking pheochromocytoma and liver dysfunction, raises important mechanistic questions concerning the relationship between catecholamines and liver function. It may also have clinical implications. Indeed, pheochromocytoma should be considered as a possible cause in case of unexplained transaminase increase associated with the recent onset of hypertension

Cross-disorder genome-wide analyses suggest a complex genetic relationship between Tourette's syndrome and OCD.

ObjectiveObsessive-compulsive disorder (OCD) and Tourette's syndrome are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identification of definitive susceptibility genes for these etiologically complex disorders remains elusive. The authors report a combined genome-wide association study (GWAS) of Tourette's syndrome and OCD.MethodThe authors conducted a GWAS in 2,723 cases (1,310 with OCD, 834 with Tourette's syndrome, 579 with OCD plus Tourette's syndrome/chronic tics), 5,667 ancestry-matched controls, and 290 OCD parent-child trios. GWAS summary statistics were examined for enrichment of functional variants associated with gene expression levels in brain regions. Polygenic score analyses were conducted to investigate the genetic architecture within and across the two disorders.ResultsAlthough no individual single-nucleotide polymorphisms (SNPs) achieved genome-wide significance, the GWAS signals were enriched for SNPs strongly associated with variations in brain gene expression levels (expression quantitative loci, or eQTLs), suggesting the presence of true functional variants that contribute to risk of these disorders. Polygenic score analyses identified a significant polygenic component for OCD (p=2×10(-4)), predicting 3.2% of the phenotypic variance in an independent data set. In contrast, Tourette's syndrome had a smaller, nonsignificant polygenic component, predicting only 0.6% of the phenotypic variance (p=0.06). No significant polygenic signal was detected across the two disorders, although the sample is likely underpowered to detect a modest shared signal. Furthermore, the OCD polygenic signal was significantly attenuated when cases with both OCD and co-occurring Tourette's syndrome/chronic tics were included in the analysis (p=0.01).ConclusionsPrevious work has shown that Tourette's syndrome and OCD have some degree of shared genetic variation. However, the data from this study suggest that there are also distinct components to the genetic architectures of these two disorders. Furthermore, OCD with co-occurring Tourette's syndrome/chronic tics may have different underlying genetic susceptibility compared with OCD alone