味觉刺激引起大鼠臂旁核神经元抑制性反应

本研究以轻度麻醉的大鼠为对象,应用细胞外微电极记录技术,观察并分析了脑桥臂旁核抑制性味觉神经元的自发活动及其对NaCl、HCl、盐酸奎宁（quinine HCl,QHCl））和蔗糖等四种基本味觉刺激的反应。共分析了18个具有自发活动的抑制性味觉神经元,自发放电频率分布在0．2～5．5Hz之间,平均放电频率（2．15±0．31）Hz。18个神经元中,1个神经元对单一味觉刺激呈抑制性反应,其余17个神经元对两种或两种以上的基本味觉刺激发生抑制性反应,且抑制具有潜伏期短、持续时间较长等特征。抑制持续时间5～80S,部分神经元表现为后抑制效应。根据神经元对四种基本味觉刺激呈抑制性反应的程度,将其分为NaCl优势神经元（n=8）,HCl优势神经元（n=3）,QHCl优势神经元n=3）和蔗糖优势神经元n=4）。其中NaCl优势神经元的反应谐宽最高（0．945）。这些神经元对欣快或厌恶刺激的区别能力较低。结果提示,在脑桥臂旁核存在对味觉刺激起抑制性反应的神经元,这些味觉神经元可能在味觉的调制及对欣快和厌恶刺激的编码中发挥重要的作用。     

Citric acid and quinine share perceived chemosensory features making oral discrimination difficult in C57BL/6J mice

Evidence in the literature shows that in rodents, some taste-responsive neurons respond to both quinine and acid stimuli. Also, under certain circumstances, rodents display some degree of difficulty in discriminating quinine and acid stimuli. Here, C57BL/6J mice were trained and tested in a 2-response operant discrimination task. Mice had severe difficulty discriminating citric acid from quinine and 6-n-propylthiouracil (PROP) with performance slightly, but significantly, above chance. In contrast, mice were able to competently discriminate sucrose from citric acid, NaCl, quinine, and PROP. In another experiment, mice that were conditioned to avoid quinine by pairings with LiCl injections subsequently suppressed licking responses to quinine and citric acid but not to NaCl or sucrose in a brief-access test, relative to NaCl-injected control animals. However, mice that were conditioned to avoid citric acid did not display cross-generalization to quinine. These mice significantly suppressed licking only to citric acid, and to a much lesser extent NaCl, compared with controls. Collectively, the findings from these experiments suggest that in mice, citric acid and quinine share chemosensory features making discrimination difficult but are not perceptually identical.     

Longitudinal Treatment Outcomes of Microsurgical Treatment of Neurosensory Deficit after Lower Third Molar Surgery: A Prospective Case Series

Objective

To prospectively evaluate the longitudinal subjective and objective outcomes of the microsurgical treatment of lingual nerve (LN) and inferior alveolar nerve (IAN) injury after third molar surgery.

Materials and Methods

A 1-year longitudinal observational study was conducted on patients who received LN or IAN repair after third molar surgery-induced nerve injury. Subjective assessments (“numbness”, “hyperaesthesia”, “pain”, “taste disturbance”, “speech” and “social life impact”) and objective assessments (light touch threshold, two-point discrimination, pain threshold, and taste discrimination) were recorded.

Results

12 patients (10 females) with 10 LN and 2 IAN repairs were recruited. The subjective outcomes at post-operative 12 months for LN and IAN repair were improved. “Pain” and “hyperaesthesia” were most drastically improved. Light touch threshold improved from 44.7g to 1.2g for LN repair and 2g to 0.5g for IAN repair.

Conclusion

Microsurgical treatment of moderate to severe LN injury after lower third molar surgery offered significant subjective and objective sensory improvements. 100% FSR was achieved at post-operative 6 months.     

Insects Can Count: Sensory Basis of Host Discrimination in Parasitoid Wasps Revealed

The solitary parasitoid Leptopilina heterotoma is one of the best studied organisms concerning the ecology, behaviour and physiology of host discrimination. Behavioural evidence shows that L. heterotoma uses its ovipositor to discriminate not only between parasitized and unparasitized Drosophila melanogaster larvae, but also to discriminate between hosts with different numbers of parasitoid eggs. The existing knowledge about how and when the parasitoid marks the host motivated us to unravel the chemosensory basis of host discrimination by L. heterotoma that allows it to choose the “best” host available. In this paper we report on electrophysiological recordings of multi-neural responses from the single taste sensillum on the tip of the unpaired ovipositor valve. We stimulated this sensillum with haemolymph of unparasitized, one-time-parasitized and two-times-parasitized Drosophila larvae. We demonstrate for the first time that quantitative characteristics of the neural responses to these haemolymph samples differed significantly, implying that host discrimination is encoded by taste receptor neurons in the multi-neuron coeloconic ovipositor sensillum. The activity of three of the six neurons present in the sensillum suffices for host discrimination and support the hypothesis that L. heterotoma females employ an ensemble code of parasitization status of the host.     

Mechanism of aluminum tolerance in snapbeans : root exudation of citric Acid

One proposed mechanism of aluminum (Al) tolerance in plants is the release of an Al-chelating compound into the rhizosphere. In this experiment, two cultivars of snapbeans (Phaseolus vulgaris L. “Romano” and “Dade”) that differ in Al tolerance were grown hydroponically with and without Al under aseptic conditions. After growth in nutrient solutions for 8 days, aliphatic and phenolic organic acids were analyzed in the culture solutions with an ion chromatograph and a high pressure liquid chromatograph. The tolerant snapbean, “Dade”, when exposed to Al, exuded citric acid into the rhizosphere in a concentration that was 70 times as great as that of “Dade” grown without Al, and 10 times as great as that of “Romano” grown with or without Al. The sensitive cultivar, “Romano”, exuded only slightly more citric acid into the growing medium under Al-stress, compared to nonstressed conditions. Citric acid is known to chelate Al strongly and to reverse its phytotoxic effects. Also, citric acid has been shown previously to enhance the availability of phosphorus (P) from insoluble Al phosphates. Thus, one mechanism of Al-tolerance in snapbeans appears to be the exudation of citric acid into the rhizosphere, induced either by toxic levels of Al or by low P due to the precipitation of insoluble Al phosphates. Our experiment was not able to distinguish between these two factors; however, tolerance to both primary and secondary Al-stress injuries are important for plants growing in Al-toxic soils.     

Responses of Primate Taste Cortex Neurons to the Astringent Tastant Tannic Acid

In order to advance knowledge of the neural control of feeding,we investigated the cortical representation of the taste oftannic acid, which produces the taste of astringency. It isa dietary component of biological importance particularly toarboreal primates. Recordings were made from 74 taste responsiveneurons in the orbitofrontal cortex. Single neurons were foundthat were tuned to respond to 0.001 M tannic acid, and representeda subpopulation of neurons that was distinct from neurons responsiveto the tastes of glucose (sweet), NaCl (salty), HCI (sour),quinine (bitter) and monosodium glutamate (umami). In addition,across the population of 74 neurons, tannic acid was as wellrepresented as the tastes of NaCI, HCI quinine or monosodiumglutamate. Multidimensional scaling analysis of the neuronalresponses to the tastants indicates that tannic acid lies outsidethe boundaries of the four conventional taste qualities (sweet,sour, bitter and salty). Taken together these data indicatethat the astringent taste of tannic acid should be consideredas a distinct taste quality, which receives a separate representationfrom sweet, salt, bitter and sour in the primate cortical tasteareas. Chem. Senses 21: 135–145, 1996.     

Predictive Habitat Modelling as a Tool to Assess the Change in Distribution and Extent of an OSPAR Priority Habitat under an Increased Ocean Temperature Scenario: Consequences for Marine Protected Area Networks and Management

The aims of this study were to determine the extent and distribution of an OSPAR priority habitat under current baseline ocean temperatures; to illustrate the prospect for habitat loss under a changing ocean temperature scenario; and to demonstrate the potential application of predictive habitat mapping in “future-proofing” conservation and biodiversity management.Maxent modelling and GIS environmental envelope analysis of the biogenic bed forming species, Modiolus modiolus was carried out. The Maxent model was tested and validated using 75%/25% training/test occurrence records and validated against two sampling biases (the whole study area and a 20km buffer). The model was compared to the envelope analysis and the area under the receiver operating characteristic curve (Area Under the curve; AUC) was evaluated.The performance of the Maxent model was rated as ‘good’ to ‘excellent’ on all replicated runs and low variation in the runs was recorded from the AUC values. The extent of “most suitable”, “less suitable” and “unsuitable” habitat was calculated for the baseline year (2009) and the projected increased ocean temperature scenarios (2030, 2050, 2080 and 2100). A loss of 100% of “most suitable” habitat was reported by 2080.Maintaining a suitable level of protection of marine habitats/species of conservation importance may require management of the decline and migration rather than maintenance of present extent. Methods applied in this study provide the initial application of a plausible “conservation management tool”.     

An expression system for Gustatory receptors—and why it failed

A recent paper by the Dahankuar laboratory suggested that single Drosophila sugar receptors proteins accurately mediate sugar detection when ectopically expressed in olfactory neurons of the antenna. These findings contra-dict numerous previously published electrophysiological and behavioral investigations, which all point towards heteromultimeric sugar taste receptors. Here, I provide some explanation why this “pseudo-heterologous” expression system may have led to this misleading conclusion.     

Is There Any Effect on Smell and Taste Functions with Levothyroxine Treatment in Subclinical Hypothyroidism?

Subclinical hypothyroidism has been accused for coronary heart disease, lipid metabolism disorders, neuropsychiatric disorders, infertility or pregnancy related problems with various strength of evidence. Currently there is insufficient knowledge about olfaction and taste functions in subclinical hypothyroidism. Aim of the present study is to investigate the degree of smell and taste dysfunction in patients with subclinical hypothyroidism. 28 subclinical hypothyroid patients, and 31 controls enrolled in the prospective study in Istanbul, Turkey. Subclinical hypothyroid patients were treated with L-thyroxine for 3 months. Psychophysiological olfactory testing was performed using odor dispensers similar to felt-tip pens (“Sniffin’ Sticks”, Burghart, Wedel, Germany). Taste function tests were made using "Taste Strips" (Burghart, Wedel, Germany) which are basically tastant adsorbed filter paper strip. Patients scored lower on psychophysical olfactory tests than controls (odor thresholds:8.1±1.0 vs 8.9±1.1, p = 0.007; odor discrimination:12.4±1.3 vs 13.1±0.9, p = 0.016; odor identification:13.1±0.9 vs 14.0±1.1, p = 0.001; TDI score: 33.8±2.4 vs 36.9±2.1, p = 0.001). In contrast, results from psychophysical gustatory tests showed only a decreased score for “bitter” in patients, but not for other tastes (5.9±1.8 vs 6.6±1.0, p = 0.045). Three month after onset of treatment olfactory test scores already indicated improvement (odor thresholds:8.1±1.0 vs 8.6±0.6, p<0.001; odor discrimination:12.4±1.31 vs 12.9±0.8, p = 0.011; odor identification:13.1±0.9 vs 13.9±0.8, p<0.001; TDI scores:33.8±2.4 vs 35.5±1.7, p<0.001) respectively. Taste functions did not differ between groups for sweet, salty and, sour tastes but bitter taste was improved after 3 months of thyroxin substitution (patients:5.9±1.8 vs 6.6±1.2, p = 0.045). Correlation of changes in smell and taste, with thyroid function test were also evaluated. TSH, fT4 were found have no correlation with smell and taste changes with treatment. However bitter taste found positively correlated with T3 with treatment(r: 0.445, p: 0.018). Subclinical hypothyroid patients exhibited a significantly decreased olfactory sensitivity; in addition, bitter taste was significantly affected. Most importantly, these deficits can be remedied on average within 3 months with adequate treatment.     

Reduction of saltiness and bitterness after a chlorhexidine rinse

Chronic rinsing with chlorhexidine, an oral-antiseptic, has been shown to decrease the saltiness of NaCl and the bitterness of quinine. The effect of acute chlorhexidine on taste has not been investigated. The purpose of the present study was to examine the effect of acute chlorhexidine rinses on taste intensity and quality of 11 stimuli representing sweet, salt, sour, bitter and savory. All stimuli were first matched for overall intensity so the effects of chlorhexidine would be directly comparable across compounds. As a control treatment, the bitter taste of chlorhexidine digluconate (0.12%) was matched in intensity to quinine HCl, which was found to cross-adapt the bitterness of chlorhexidine. Subjects participated in four experimental conditions: a pre-test, a quinine treatment, a chlorhexidine treatment, and a post-test condition, while rating total taste intensity and taste qualities in separate test sessions. Relative to the quinine treatment, chlorhexidine was found to decrease the salty taste of NaCl, KCl and NH4Cl, and not to significantly affect the tastes of sucrose, monosodium glutamate (MSG), citric acid, HCl and the taste of water. The bitter taste of urea, sucrose octa-acetate and quinine were suppressed after chlorhexidine rinses relative to water rinses, but were only marginally suppressed relative to quinine rinses. Potential mechanisms are discussed.     

Taste profiles from single circumvallate papillae: comparison with fungiform profiles

Two experiments were conducted to investigate the psychophysicalresponse characteristics of single circumvallate papillae. InExperiment 1, 12 circumvallate papillae in four subjects werechemically stimulated to assess identification of taste qualities.Single circumvallate papillae were found to mediate multipletaste qualities, and the taste profiles obtained from differentpapillae were similar within the same subject. Moreover, sucrose,quinine monohydrochloride and citric acid elicited unitary andcharacteristic quality responding in these papillae from allsubjects, whereas NaCl elicited predominantly sour and/or bitterresponses from three of the four subjects. Experiment 2 directly compared responses obtained from singlecircumvallate papillae with those obtained from fungiform regionsof the tongue. Data for 10 subjects showed significantly greatersour responses to citric acid and NaCl in circumvallate papillaeand significantly greater salty responses to these compoundson the anterior tongue. In addition, the taste profiles forcitric acid and NaCl were distinct for circumvallate papillae,while those from the anterior tongue were similar. These datasuggest that the bitterness and sweetness of quinine and sugar,respectively, can be identified on the basis of sensory informationarising from either circumvallate or fungiform regions, butthat differentiation of the tastes of salts and acids may dependon a comparison of the input from both regions and/or additionalinformation arising from foliate regions.     

Analysis of 567,758 randomized controlled trials published over 30 years reveals trends in phrases used to discuss results that do not reach statistical significance

The power of language to modify the reader’s perception of interpreting biomedical results cannot be underestimated. Misreporting and misinterpretation are pressing problems in randomized controlled trials (RCT) output. This may be partially related to the statistical significance paradigm used in clinical trials centered around a P value below 0.05 cutoff. Strict use of this P value may lead to strategies of clinical researchers to describe their clinical results with P values approaching but not reaching the threshold to be “almost significant.” The question is how phrases expressing nonsignificant results have been reported in RCTs over the past 30 years. To this end, we conducted a quantitative analysis of English full texts containing 567,758 RCTs recorded in PubMed between 1990 and 2020 (81.5% of all published RCTs in PubMed). We determined the exact presence of 505 predefined phrases denoting results that approach but do not cross the line of formal statistical significance (P < 0.05). We modeled temporal trends in phrase data with Bayesian linear regression. Evidence for temporal change was obtained through Bayes factor (BF) analysis. In a randomly sampled subset, the associated P values were manually extracted. We identified 61,741 phrases in 49,134 RCTs indicating almost significant results (8.65%; 95% confidence interval (CI): 8.58% to 8.73%). The overall prevalence of these phrases remained stable over time, with the most prevalent phrases being “marginally significant” (in 7,735 RCTs), “all but significant” (7,015), “a nonsignificant trend” (3,442), “failed to reach statistical significance” (2,578), and “a strong trend” (1,700). The strongest evidence for an increased temporal prevalence was found for “a numerical trend,” “a positive trend,” “an increasing trend,” and “nominally significant.” In contrast, the phrases “all but significant,” “approaches statistical significance,” “did not quite reach statistical significance,” “difference was apparent,” “failed to reach statistical significance,” and “not quite significant” decreased over time. In a random sampled subset of 29,000 phrases, the manually identified and corresponding 11,926 P values, 68,1% ranged between 0.05 and 0.15 (CI: 67. to 69.0; median 0.06). Our results show that RCT reports regularly contain specific phrases describing marginally nonsignificant results to report P values close to but above the dominant 0.05 cutoff. The fact that the prevalence of the phrases remained stable over time indicates that this practice of broadly interpreting P values close to a predefined threshold remains prevalent. To enhance responsible and transparent interpretation of RCT results, researchers, clinicians, reviewers, and editors may reduce the focus on formal statistical significance thresholds and stimulate reporting of P values with corresponding effect sizes and CIs and focus on the clinical relevance of the statistical difference found in RCTs.

The power of language to modify the reader’s perception of interpreting biomedical results cannot be underestimated. An analysis of more than half a million randomized controlled trials reveals that researchers are using appealing phrases to describe non-significant findings as if they were below the p=0.05 significance threshold.     

Sensitivity of Rat Cortical Neurons in Distinguishing Taste Qualities by Individual and Correlative Activities

To examine the possibility that different taste qualities arerepresented by the correlative activity of cortical gustatoryneurons, we made simultaneous recordings of neuron pairs duringapplication of four basic tastes into the oral cavity of anesthetizedrats and the following observations were made: (i) in 30 of67 pairs of taste responsive neurons, peaks (troughs in a fewcases) were produced in the cross-correlograms (CCs) duringstimulation with some tastants; (ii) the correlative dischargesoccupied 6–8% of the total spikes discharged by individualneurons during taste stimulation and occurred, in a considerablenumber of cases, even during stimulation with tastants to whichone or both of the component neurons of a pair were apparentlynon-responding (often sucrose and quinine); (iii) the numberof tastants to which a neuron pair responded with a significantcorrelative activity was often greater than the number of tastantsto which the component neurons of the same pair responded withsignificant changes in discharge rate; (iv) there was no significantdifference between the correlative (formation of peaks or troughsin the CC) and individual (change in discharge rate of individualneurons) ways of coding in the sensitivity to distinguish betweentwo taste qualities ranked to be adjacent on the basis of thenumber of spikes composing the response; and (v) the peaks ortroughs appearing in two CCs during stimulations with two kindsof tastants were compared with regard to overlapping of theirdelay ranges and widths. The spikes in the non-overlapping portionof each peak (suppressed spike number in the case of troughs)are supposed to be able to contribute to two-taste discrimination:the correlated discharges occurring with a delay time that correspondsto the overlapping portion can in no way be judged differently,but the spikes falling in the non-overlapping portion may contributeto the differentiation. The ratio of the non-overlapping portionto the entire peak (or trough) was 0.35 on average. It is concludedthat temporal coding of taste qualities seems to operate effectivelyin the gustatory cortex. Chem. Senses 22: 363–373, 1997.     

Hierarchical processing of auditory objects in humans

This work examines the computational architecture used by the brain during the analysis of the spectral envelope of sounds, an important acoustic feature for defining auditory objects. Dynamic causal modelling and Bayesian model selection were used to evaluate a family of 16 network models explaining functional magnetic resonance imaging responses in the right temporal lobe during spectral envelope analysis. The models encode different hypotheses about the effective connectivity between Heschl's Gyrus (HG), containing the primary auditory cortex, planum temporale (PT), and superior temporal sulcus (STS), and the modulation of that coupling during spectral envelope analysis. In particular, we aimed to determine whether information processing during spectral envelope analysis takes place in a serial or parallel fashion. The analysis provides strong support for a serial architecture with connections from HG to PT and from PT to STS and an increase of the HG to PT connection during spectral envelope analysis. The work supports a computational model of auditory object processing, based on the abstraction of spectro-temporal “templates” in the PT before further analysis of the abstracted form in anterior temporal lobe areas.     

Quantifying Auditory Temporal Stability in a Large Database of Recorded Music

“Moving to the beat” is both one of the most basic and one of the most profound means by which humans (and a few other species) interact with music. Computer algorithms that detect the precise temporal location of beats (i.e., pulses of musical “energy”) in recorded music have important practical applications, such as the creation of playlists with a particular tempo for rehabilitation (e.g., rhythmic gait training), exercise (e.g., jogging), or entertainment (e.g., continuous dance mixes). Although several such algorithms return simple point estimates of an audio file’s temporal structure (e.g., “average tempo”, “time signature”), none has sought to quantify the temporal stability of a series of detected beats. Such a method-a “Balanced Evaluation of Auditory Temporal Stability” (BEATS)–is proposed here, and is illustrated using the Million Song Dataset (a collection of audio features and music metadata for nearly one million audio files). A publically accessible web interface is also presented, which combines the thresholdable statistics of BEATS with queryable metadata terms, fostering potential avenues of research and facilitating the creation of highly personalized music playlists for clinical or recreational applications.     

Characterization of the Denitrification-Associated Phosphorus Uptake Properties of “Candidatus Accumulibacter phosphatis” Clades in Sludge Subjected to Enhanced Biological Phosphorus Removal

To characterize the denitrifying phosphorus (P) uptake properties of “Candidatus Accumulibacter phosphatis,” a sequencing batch reactor (SBR) was operated with acetate. The SBR operation was gradually acclimated from anaerobic-oxic (AO) to anaerobic-anoxic-oxic (A2O) conditions by stepwise increases of nitrate concentration and the anoxic time. The communities of “Ca. Accumulibacter” and associated bacteria at the initial (AO) and final (A2O) stages were compared using 16S rRNA and polyphosphate kinase genes and using fluorescence in situ hybridization (FISH). The acclimation process led to a clear shift in the relative abundances of recognized “Ca. Accumulibacter” subpopulations from clades IIA > IA > IIF to clades IIC > IA > IIF, as well as to increases in the abundance of other associated bacteria (Dechloromonas [from 1.2% to 19.2%] and “Candidatus Competibacter phosphatis” [from 16.4% to 20.0%]), while the overall “Ca. Accumulibacter” abundance decreased (from 55.1% to 29.2%). A series of batch experiments combined with FISH/microautoradiography (MAR) analyses was performed to characterize the denitrifying P uptake properties of the “Ca. Accumulibacter” clades. In FISH/MAR experiments using slightly diluted sludge (∼0.5 g/liter), all “Ca. Accumulibacter” clades successfully took up phosphorus in the presence of nitrate. However, the “Ca. Accumulibacter” clades showed no P uptake in the presence of nitrate when the sludge was highly diluted (∼0.005 g/liter); under these conditions, reduction of nitrate to nitrite did not occur, whereas P uptake by “Ca. Accumulibacter” clades occurred when nitrite was added. These results suggest that the “Ca. Accumulibacter” cells lack nitrate reduction capabilities and that P uptake by “Ca. Accumulibacter” is dependent upon nitrite generated by associated nitrate-reducing bacteria such as Dechloromonas and “Ca. Competibacter.”     

Effects of Biogents Sentinel Trap Field Placement on Capture Rates of Adult Asian Tiger Mosquitoes,Aedes albopictus

The Biogents® Sentinel (BGS) trap is the standard tool to monitor adult Aedes (Stegomyia) albopictus (Skuse) (Diptera: Culicidae), the Asian tiger mosquito. BGS traps are commonly placed in residential properties during surveillance operations, but locations within properties may have significant differences in ambient light, temperature, and humidity (e.g. between a sunlit lawn and shady underbrush). We examined the effect of BGS trap placement on Ae. albopictus capture rates in three residential properties in Monmouth County, New Jersey, USA. In each property we visually selected locations as shade, partial shade, and sun. Traps in “partial shade” locations were under vegetation and were exposed to filtered sunlight during some parts of the day while “shaded” locations were never exposed to direct sunlight. Locations defined as “sun” were exposed to direct sunlight for large parts of the day. We placed a BGS trap in each of the three location types and used small data loggers to measure temperature, relative humidity, and light exposure at each trap during a 24-hour deployment. To address temporal variability, we made seven separate measurements from 31 August to 22 September 2010. We found that “partial shade” and “full shade” locations did not differ but that “full sun” locations had significantly higher light exposure, higher temperature, and lower humidity. Importantly, Ae. albopictus catches (males, females, or both) were consistently and significantly over 3 times higher in traps located in shaded locations. To further investigate the effects of local temperature and humidity on surveillance we examined Ae. albopictus collections from 37 BGS traps fitted with data loggers and deployed weekly from August through mid October, during the 2009 season, in three urban sites in Mercer County, NJ. We confirmed that local climate influences capture rates and that Ae. albopictus surveillance projects need to monitor trap placement carefully for maximum efficiency.     

GABAA Receptors Containing ρ1 Subunits Contribute to In Vivo Effects of Ethanol in Mice

GABA_A receptors consisting of ρ1, ρ2, or ρ3 subunits in homo- or hetero-pentamers have been studied mainly in retina but are detected in many brain regions. Receptors formed from ρ1 are inhibited by low ethanol concentrations, and family-based association analyses have linked ρ subunit genes with alcohol dependence. We determined if genetic deletion of ρ1 in mice altered in vivo ethanol effects. Null mutant male mice showed reduced ethanol consumption and preference in a two-bottle choice test with no differences in preference for saccharin or quinine. Null mutant mice of both sexes demonstrated longer duration of ethanol-induced loss of righting reflex (LORR), and males were more sensitive to ethanol-induced motor sedation. In contrast, ρ1 null mice showed faster recovery from acute motor incoordination produced by ethanol. Null mutant females were less sensitive to ethanol-induced development of conditioned taste aversion. Measurement of mRNA levels in cerebellum showed that deletion of ρ1 did not change expression of ρ2, α2, or α6 GABA_A receptor subunits. (S)-4-amino-cyclopent-1-enyl butylphosphinic acid (“ρ1” antagonist), when administered to wild type mice, mimicked the changes that ethanol induced in ρ1 null mice (LORR and rotarod tests), but the ρ1 antagonist did not produce these effects in ρ1 null mice. In contrast, (R)-4-amino-cyclopent-1-enyl butylphosphinic acid (“ρ2” antagonist) did not change ethanol actions in wild type but produced effects in mice lacking ρ1 that were opposite of the effects of deleting (or inhibiting) ρ1. These results suggest that ρ1 has a predominant role in two in vivo effects of ethanol, and a role for ρ2 may be revealed when ρ1 is deleted. We also found that ethanol produces similar inhibition of function of recombinant ρ1 and ρ2 receptors. These data indicate that ethanol action on GABA_A receptors containing ρ1/ρ2 subunits may be important for specific effects of ethanol in vivo.     

Auditory Stimuli Mimicking Ambient Sounds Drive Temporal “Delta-Brushes” in Premature Infants

In the premature infant, somatosensory and visual stimuli trigger an immature electroencephalographic (EEG) pattern, “delta-brushes,” in the corresponding sensory cortical areas. Whether auditory stimuli evoke delta-brushes in the premature auditory cortex has not been reported. Here, responses to auditory stimuli were studied in 46 premature infants without neurologic risk aged 31 to 38 postmenstrual weeks (PMW) during routine EEG recording. Stimuli consisted of either low-volume technogenic “clicks” near the background noise level of the neonatal care unit, or a human voice at conversational sound level. Stimuli were administrated pseudo-randomly during quiet and active sleep. In another protocol, the cortical response to a composite stimulus (“click” and voice) was manually triggered during EEG hypoactive periods of quiet sleep. Cortical responses were analyzed by event detection, power frequency analysis and stimulus locked averaging. Before 34 PMW, both voice and “click” stimuli evoked cortical responses with similar frequency-power topographic characteristics, namely a temporal negative slow-wave and rapid oscillations similar to spontaneous delta-brushes. Responses to composite stimuli also showed a maximal frequency-power increase in temporal areas before 35 PMW. From 34 PMW the topography of responses in quiet sleep was different for “click” and voice stimuli: responses to “clicks” became diffuse but responses to voice remained limited to temporal areas. After the age of 35 PMW auditory evoked delta-brushes progressively disappeared and were replaced by a low amplitude response in the same location. Our data show that auditory stimuli mimicking ambient sounds efficiently evoke delta-brushes in temporal areas in the premature infant before 35 PMW. Along with findings in other sensory modalities (visual and somatosensory), these findings suggest that sensory driven delta-brushes represent a ubiquitous feature of the human sensory cortex during fetal stages and provide a potential test of functional cortical maturation during fetal development.