Toxic effects of nanomaterials for health applications: How automation can support a systematic review of the literature?

Systematic reviews of the scientific literature can be an important source of information supporting the daily work of the regulators in their decision making, particularly in areas of innovative technologies where the regulatory experience is still limited. Significant research activities in the field of nanotechnology resulted in a huge number of publications in the last decades. However, even if the published data can provide relevant information, scientific articles are often of diverse quality, and it is nearly impossible to manually process and evaluate such amount of data in a systematic manner. In this feasibility study, we investigated to what extent open-access automation tools can support a systematic review of toxic effects of nanomaterials for health applications reported in the scientific literature. In this study, we used a battery of available tools to perform the initial steps of a systematic review such as targeted searches, data curation and abstract screening. This work was complemented with an in-house developed tool that allowed us to extract specific sections of the articles such as the materials and methods part or the results section where we could perform subsequent text analysis. We ranked the articles according to quality criteria based on the reported nanomaterial characterisation and extracted most frequently described toxic effects induced by different types of nanomaterials. Even if further demonstration of the reliability and applicability of automation tools is necessary, this study demonstrated the potential to leverage information from the scientific literature by using automation systems in a tiered strategy.

N-glycome analysis detects dysglycosylation missed by conventional methods in SLC39A8 deficiency.

Congenital disorders of glycosylation (CDG) are a growing group of inborn metabolic disorders with multiorgan presentation. SLC39A8-CDG is a severe subtype caused by biallelic mutations in the manganese transporter SLC39A8, reducing levels of this essential cofactor for many enzymes including glycosyltransferases. The current diagnostic standard for disorders of N-glycosylation is the analysis of serum transferrin. Exome and Sanger sequencing were performed in two patients with severe neurodevelopmental phenotypes suggestive of CDG. Transferrin glycosylation was analyzed by high-performance liquid chromatography (HPLC) and isoelectric focusing in addition to comprehensive N-glycome analysis using matrix-assisted laser desorption ionization time of flight (MALDI-TOF) mass spectrometry (MS). Atomic absorption spectroscopy was used to quantify whole blood manganese levels. Both patients presented with a severe, multisystem disorder, and a complex neurological phenotype. Magnetic resonance imaging (MRI) revealed a Leigh-like syndrome with bilateral T2 hyperintensities of the basal ganglia. In patient 1, exome sequencing identified the previously undescribed homozygous variant c.608T>C [p.F203S] in SLC39A8. Patient 2 was found to be homozygous for c.112G>C [p.G38R]. Both individuals showed a reduction of whole blood manganese, though transferrin glycosylation was normal. N-glycome using MALDI-TOF MS identified an increase of the asialo-agalactosylated precursor N-glycan A2G1S1 and a decrease in bisected structures. In addition, analysis of heterozygous CDG-allele carriers identified similar but less severe glycosylation changes. Despite its reliance as a clinical gold standard, analysis of transferrin glycosylation cannot be categorically used to rule out SLC39A8-CDG. These results emphasize that SLC39A8-CDG presents as a spectrum of dysregulated glycosylation, and MS is an important tool for identifying deficiencies not detected by conventional methods.

The Neural Basis of Dim-Light Vision in Echolocating Bats.

Echolocating bats evolved a sophisticated biosonar imaging system that allows for a life in dim-light habitats. However, especially for far-range operations such as homing, bats can support biosonar by vision. Large eyes and a retina that mainly consists of rods are assumed to be the optical adjustments that enable bats to use visual information at low light levels. In addition to optical mechanisms, many nocturnal animals evolved neural adaptations such as elongated integration times or enlarged spatial sampling areas to further increase the sensitivity of their visual system by temporal or spatial summation of visual information. The neural mechanisms that underlie the visual capabilities of echolocating bats have, however, so far not been investigated. To shed light on spatial and temporal response characteristics of visual neurons in an echolocating bat, Phyllostomus discolor, we recorded extracellular multiunit activity in the retino-recipient superficial layers of the superior colliculus (SC). We discovered that response latencies of these neurons were generally in the mammalian range, whereas neural spatial sampling areas were unusually large compared to those measured in the SC of other mammals. From this we suggest that echolocating bats likely use spatial but not temporal summation of visual input to improve visual performance under dim-light conditions. Furthermore, we hypothesize that bats compensate for the loss of visual spatial precision, which is a byproduct of spatial summation, by integration of spatial information provided by both the visual and the biosonar systems. Given that knowledge about neural adaptations to dim-light vision is mainly based on studies done in non-mammalian species, our novel data provide a valuable contribution to the field and demonstrate the suitability of echolocating bats as a nocturnal animal model to study the neurophysiological aspects of dim-light vision.

From Perception to Action: The Role of Auditory Input in Shaping Vocal Communication and Social Behaviors in Birds.

Acoustic communication signals are typically generated to influence the behavior of conspecific receivers. In songbirds, for instance, such cues are routinely used by males to influence the behavior of females and rival males. There is remarkable diversity in vocalizations across songbird species, and the mechanisms of vocal production have been studied extensively, yet there has been comparatively little emphasis on how the receiver perceives those signals and uses that information to direct subsequent actions. Here, we emphasize the receiver as an active participant in the communication process. The roles of sender and receiver can alternate between individuals, resulting in an emergent feedback loop that governs the behavior of both. We describe three lines of research that are beginning to reveal the neural mechanisms that underlie the reciprocal exchange of information in communication. These lines of research focus on the perception of the repertoire of songbird vocalizations, evaluation of vocalizations in mate choice, and the coordination of duet singing.

Bridging communities in the field of nanomedicine.

An early dialogue between nanomedicine developers and regulatory authorities are of utmost importance to anticipate quality and safety requirements for these innovative health products. In order to stimulate interactions between the various communities involved in a translation of nanomedicines to clinical applications, the European Commission's Joint Research Centre hosted a workshop titled "Bridging communities in the field of Nanomedicine" in Ispra/Italy on the 27th -28th September 2017. Experts from regulatory bodies, research institutions and industry came together to discuss the next generation of nanomedicines and their needs to obtain regulatory approval. The workshop participants came up with recommendations highlighting methodological gaps that should be addressed in ongoing projects addressing the regulatory science of nanomedicines. In addition, individual opinions of experts relevant to progress of the regulatory science in the field of nanomedicine were summarised in the format of a survey.

Patient complaints as a means to improve quality of hospital care. Results of a qualitative content analysis / Patientenrückmeldung als Möglichkeit die Versorgungsqualität von Spitalpatienten zu verbessern. Ergebnisse einer qualitativen Inhaltsanalyse

Background: Many hospitals have defined procedures for a complaint management. A systematic analysis of patient complaints helps to identify similar complaints and patterns so that targeted improvement measures can be derived (Gallagher & Mazor, 2015). Aim: Our three-month, nurse-led practice development project aimed 1) to identify complaints regarding communication issues, 2) to systemise and prioritise complaints regarding communication issues, and 3) to derive clinic-specific recommendations for improvement. Method: We analysed 273 complaints of patients documented by the quality management (secondary data analysis). Using content analysis and applying the coding taxonomy for inpatient complaints by Reader, Gillespie and Roberts (2014), we distinguished communication-related complaints. By further inductive differentiation of these complaints, we identified patterns and prioritised fields of action. Results: We identified 186 communication-related complaints divided into 16 subcategories. For each subcategory, improvement interventions were derived, discussed and prioritised. Conclusions: Thus, patient complaints provided an excellent opportunity for reflection and workplace learning for nurses. The analysis gave impulse to exemplify the subject "person-centered care" for nurses.

Analysis of adverse events as a contribution to safety culture in the context of practice development / Die Analyse unerwünschter Ereignisse als Beitrag zur Sicherheitskultur im Kontext der Praxisentwicklung.

Background: Analysing adverse events is an effective patient safety measure. Aim: We show, how clinical nurse specialists have been enabled to analyse adverse events with the "Learning from Defects-Tool" (LFD-Tool). Method: Our multi-component implementation strategy addressed both, the safety knowledge of clinical nurse specialists and their attitude towards patient safety. The culture of practice development was taken into account. Results: Clinical nurse specialists relate competency building on patient safety due to the application of the LFD-tool. Applying the tool, fosters the reflection of adverse events in care teams. Conclusion: Applying the "Learning from Defects-Tool" promotes work-based learning. Analysing adverse events with the "Learning from Defects-Tool" contributes to the safety culture in a hospital.

Congruent representation of visual and acoustic space in the superior colliculus of the echolocating bat Phyllostomus discolor.

The midbrain superior colliculus (SC) commonly features a retinotopic representation of visual space in its superficial layers, which is congruent with maps formed by multisensory neurons and motor neurons in its deep layers. Information flow between layers is suggested to enable the SC to mediate goal-directed orienting movements. While most mammals strongly rely on vision for orienting, some species such as echolocating bats have developed alternative strategies, which raises the question how sensory maps are organized in these animals. We probed the visual system of the echolocating bat Phyllostomus discolor and found that binocular high acuity vision is frontally oriented and thus aligned with the biosonar system, whereas monocular visual fields cover a large area of peripheral space. For the first time in echolocating bats, we could show that in contrast with other mammals, visual processing is restricted to the superficial layers of the SC. The topographic representation of visual space, however, followed the general mammalian pattern. In addition, we found a clear topographic representation of sound azimuth in the deeper collicular layers, which was congruent with the superficial visual space map and with a previously documented map of orienting movements. Especially for bats navigating at high speed in densely structured environments, it is vitally important to transfer and coordinate spatial information between sensors and motor systems. Here, we demonstrate first evidence for the existence of congruent maps of sensory space in the bat SC that might serve to generate a unified representation of the environment to guide motor actions.

Biosonar navigation above water II: exploiting mirror images.

As in vision, acoustic signals can be reflected by a smooth surface creating an acoustic mirror image. Water bodies represent the only naturally occurring horizontal and acoustically smooth surfaces. Echolocating bats flying over smooth water bodies encounter echo-acoustic mirror images of objects above the surface. Here, we combined an electrophysiological approach with a behavioral experimental paradigm to investigate whether bats can exploit echo-acoustic mirror images for navigation and how these mirrorlike echo-acoustic cues are encoded in their auditory cortex. In an obstacle-avoidance task where the obstacles could only be detected via their echo-acoustic mirror images, most bats spontaneously exploited these cues for navigation. Sonar ensonifications along the bats' flight path revealed conspicuous changes of the reflection patterns with slightly increased target strengths at relatively long echo delays corresponding to the longer acoustic paths from the mirrored obstacles. Recordings of cortical spatiotemporal response maps (STRMs) describe the tuning of a unit across the dimensions of elevation and time. The majority of cortical single and multiunits showed a special spatiotemporal pattern of excitatory areas in their STRM indicating a preference for echoes with (relative to the setup dimensions) long delays and, interestingly, from low elevations. This neural preference could effectively encode a reflection pattern as it would be perceived by an echolocating bat detecting an object mirrored from below. The current study provides both behavioral and neurophysiological evidence that echo-acoustic mirror images can be exploited by bats for obstacle avoidance. This capability effectively supports echo-acoustic navigation in highly cluttered natural habitats.

Biosonar navigation above water I: estimating flight height.

Locomotion and foraging on the wing require precise navigation in more than just the horizontal plane. Navigation in three dimensions and, specifically, precise adjustment of flight height are essential for flying animals. Echolocating bats drink from water surfaces in flight, which requires an exceptionally precise vertical navigation. Here, we exploit this behavior in the bat, Phyllostomus discolor, to understand the biophysical and neural mechanisms that allow for sonar-guided navigation in the vertical plane. In a set of behavioral experiments, we show that for echolocating bats, adjustment of flight height depends on the tragus in their outer ears. Specifically, the tragus imposes elevation-specific spectral interference patterns on the echoes of the bats' sonar emissions. Head-related transfer functions of our bats show that these interference patterns are most conspicuous in the frequency range ∼55 kHz. This conspicuousness is faithfully preserved in the frequency tuning and spatial receptive fields of cortical single and multiunits recorded from anesthetized animals. In addition, we recorded vertical spatiotemporal response maps that describe neural tuning in elevation over time. One class of units that were very sharply tuned to frequencies ∼55 kHz showed unusual spatiotemporal response characteristics with a preference for paired echoes where especially the first echo originates from very low elevations. These behavioral and neural data provide the first insight into biosonar-based processing and perception of acoustic elevation cues that are essential for bats to navigate in three-dimensional space.

Evaluation of implementation, compliance and acceptance of partial smoking bans among hospitality workers before and after the Swiss Tobacco Control Act.

BACKGROUND: The World Health Organization recommends uniform comprehensive smoking bans in public places. In Switzerland, regulations differ between various areas and are mostly incomplete for hospitality venues. As ambiguous regulations offer more leeway for implementation, we evaluated the Swiss regulations with respect to their effects on implementation, acceptance and compliance among hospitality workers. METHODS: In our longitudinal study, a standardized, self-administered questionnaire was mailed to a sample of 185 hospitality workers before and 4-6 month after the smoking ban came into effect. The matched longitudinal sample comprised 71 participants (repeated response rate 38.4%). We developed a seven-item acceptance scale. Logistic regressions were performed to explore the factors associated with acceptance. RESULTS: Acceptance of smoking bans was influenced by smoking status and perceived annoyance with second-hand smoke in private. Although not statistically significant (P = 0.09), we found some indications that post-ban acceptance increased in an area with strict regulations, whereas it decreased in two areas with less stringent regulations. CONCLUSIONS: Tobacco bans in Swiss hospitality venues are still in a period of consolidation. The incomplete nature of the law may also have had a negative impact on the development of greater acceptance.

Development of a pluripotent stem cell derived neuronal model to identify chemically induced pathway perturbations in relation to neurotoxicity: effects of CREB pathway inhibition.

According to the advocated paradigm shift in toxicology, acquisition of knowledge on the mechanisms underlying the toxicity of chemicals, such as perturbations of biological pathways, is of primary interest. Pluripotent stem cells (PSCs), such as human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), offer a unique opportunity to derive physiologically relevant human cell types to measure molecular and cellular effects of such pathway modulations. Here we compared the neuronal differentiation propensity of hESCs and hiPSCs with the aim to develop novel hiPSC-based tools for measuring pathway perturbation in relation to molecular and cellular effects in vitro. Among other fundamental pathways, also, the cAMP responsive element binding protein (CREB) pathway was activated in our neuronal models and gave us the opportunity to study time-dependent effects elicited by chemical perturbations of the CREB pathway in relation to cellular effects. We show that the inhibition of the CREB pathway, using 2-naphthol-AS-E-phosphate (KG-501), induced an inhibition of neurite outgrowth and synaptogenesis, as well as a decrease of MAP2(+) neuronal cells. These data indicate that a CREB pathway inhibition can be related to molecular and cellular effects that may be relevant for neurotoxicity testing, and, thus, qualify the use of our hiPSC-derived neuronal model for studying chemical-induced neurotoxicity resulting from pathway perturbations.

Spatiotemporal contrast enhancement and feature extraction in the bat auditory midbrain and cortex.

Navigating on the wing in complete darkness is a challenging task for echolocating bats. It requires the detailed analysis of spatial and temporal information gained through echolocation. Thus neural encoding of spatiotemporal echo information is a major function in the bat auditory system. In this study we presented echoes in virtual acoustic space and used a reverse-correlation technique to investigate the spatiotemporal response characteristics of units in the inferior colliculus (IC) and the auditory cortex (AC) of the bat Phyllostomus discolor. Spatiotemporal response maps (STRMs) of IC units revealed an organization of suppressive and excitatory regions that provided pronounced contrast enhancement along both the time and azimuth axes. Most IC units showed either spatially centralized short-latency excitation spatiotemporally imbedded in strong suppression, or the opposite, i.e., central short-latency suppression imbedded in excitation. This complementary arrangement of excitation and suppression was very rarely seen in AC units. In contrast, STRMs in the AC revealed much less suppression, sharper spatiotemporal tuning, and often a special spatiotemporal arrangement of two excitatory regions. Temporal separation of excitatory regions ranged up to 25 ms and was thus in the range of temporal delays occurring in target ranging in bats in a natural situation. Our data indicate that spatiotemporal processing of echo information in the bat auditory midbrain and cortex serves very different purposes: Whereas the spatiotemporal contrast enhancement provided by the IC contributes to echo-feature extraction, the AC reflects the result of this processing in terms of a high selectivity and task-oriented recombination of the extracted features.

Impact of a smoking ban in hospitality venues on second hand smoke exposure: a comparison of exposure assessment methods.

BACKGROUND: In May 2010, Switzerland introduced a heterogeneous smoking ban in the hospitality sector. While the law leaves room for exceptions in some cantons, it is comprehensive in others. This longitudinal study uses different measurement methods to examine airborne nicotine levels in hospitality venues and the level of personal exposure of non-smoking hospitality workers before and after implementation of the law. METHODS: Personal exposure to second hand smoke (SHS) was measured by three different methods. We compared a passive sampler called MoNIC (Monitor of NICotine) badge, to salivary cotinine and nicotine concentration as well as questionnaire data. Badges allowed the number of passively smoked cigarettes to be estimated. They were placed at the venues as well as distributed to the participants for personal measurements. To assess personal exposure at work, a time-weighted average of the workplace badge measurements was calculated. RESULTS: Prior to the ban, smoke-exposed hospitality venues yielded a mean badge value of 4.48 (95%-CI: 3.7 to 5.25; n = 214) cigarette equivalents/day. At follow-up, measurements in venues that had implemented a smoking ban significantly declined to an average of 0.31 (0.17 to 0.45; n = 37) (p = 0.001). Personal badge measurements also significantly decreased from an average of 2.18 (1.31-3.05 n = 53) to 0.25 (0.13-0.36; n = 41) (p = 0.001). Spearman rank correlations between badge exposure measures and salivary measures were small to moderate (0.3 at maximum). CONCLUSIONS: Nicotine levels significantly decreased in all types of hospitality venues after implementation of the smoking ban. In-depth analyses demonstrated that a time-weighted average of the workplace badge measurements represented typical personal SHS exposure at work more reliably than personal exposure measures such as salivary cotinine and nicotine.

Inter-Individual Variations: A Challenge for the Standardisation of Complement Activation Assays.

Introduction: The role of the human immune system in pathologic responses to chemicals including nanomaterials was identified as a gap in current hazard assessments. However, the complexity of the human immune system as well as interspecies variations make the development of predictive toxicity tests challenging. In the present study, we have analysed to what extent fluctuations of the complement system of different individuals will have an impact on the standardisation of immunological tests. Methods: We treated commercially available pooled sera (PS) from healthy males, individual sera from healthy donors and from patients suffering from cancer, immunodeficiency and allergies with small molecules and liposomes. Changes of iC3b protein levels measured in enzyme-linked immunosorbent assays served as biomarker for complement activation. Results: The level of complement activation in PS differed significantly from responses of individual donors (p < 0.01). Only seven out of 32 investigated sera from healthy donors responded similarly to the pooled serum. This variability was even more remarkable when investigating the effect of liposomes on the complement activation in sera from donors with pre-existing pathologies. Neither the 26 sera of donors with allergies nor sera of 16 donors with immunodeficiency responded similar to the PS of healthy donors. Allergy sufferers showed an increase in iC3b levels of 4.16-fold changes when compared to PS treated with liposomes. Discussion: Our studies demonstrate that the use of pooled serum can lead to an over- or under-estimation of immunological response in particular for individuals with pre-existing pathologies. This is of high relevance when developing medical products based on nanomaterials and asks for a review of the current practice to use PS from healthy donors for the prediction of immunological effects of drugs in patients. A better understanding of individual toxicological responses to xenobiotics should be an essential part in safety assessments.

The sonar aperture and its neural representation in bats.

As opposed to visual imaging, biosonar imaging of spatial object properties represents a challenge for the auditory system because its sensory epithelium is not arranged along space axes. For echolocating bats, object width is encoded by the amplitude of its echo (echo intensity) but also by the naturally covarying spread of angles of incidence from which the echoes impinge on the bat's ears (sonar aperture). It is unclear whether bats use the echo intensity and/or the sonar aperture to estimate an object's width. We addressed this question in a combined psychophysical and electrophysiological approach. In three virtual-object playback experiments, bats of the species Phyllostomus discolor had to discriminate simple reflections of their own echolocation calls differing in echo intensity, sonar aperture, or both. Discrimination performance for objects with physically correct covariation of sonar aperture and echo intensity ("object width") did not differ from discrimination performances when only the sonar aperture was varied. Thus, the bats were able to detect changes in object width in the absence of intensity cues. The psychophysical results are reflected in the responses of a population of units in the auditory midbrain and cortex that responded strongest to echoes from objects with a specific sonar aperture, regardless of variations in echo intensity. Neurometric functions obtained from cortical units encoding the sonar aperture are sufficient to explain the behavioral performance of the bats. These current data show that the sonar aperture is a behaviorally relevant and reliably encoded cue for object size in bat sonar.

Vision and vocal communication guide three-dimensional spatial coordination of zebra finches during wind-tunnel flights.

Animal collective motion is a natural phenomenon readily observable in various taxa. Although theoretical models can predict the macroscopic pattern of group movements based on the relative spatial position of group members, it is poorly understood how group members exchange directional information, which enables the spatial coordination between individuals during collective motion. To test if vocalizations emitted during flocking flight are used by birds to transmit directional information between group members, we recorded vocal behaviour, head orientation and spatial position of each individual in a small flock of zebra finches (Taeniopygia guttata) flying in a wind tunnel. We found that the finches can use both visual and acoustic cues for three-dimensional flock coordination. When visual information is insufficient, birds can increasingly exploit active vocal communication to avoid collisions with flock mates. Our study furthers the mechanistic understanding of collective motion in birds and highlights the impact interindividual vocal interactions can have on group performances in these animals.

Tiered testing of micro- and nanoplastics using intestinal in vitro models to support hazard assessments.

The uncertainty of potential risks associated with micro- and nanoplastics (MNPs) are of growing public concern. However, the diversity of MNPs in the environment makes a systematic analysis of potential health effects challenging. New tools and approaches are necessary to investigate biological effects of MNPs. With this quick scoping review, we aim to analyse the suitability of in vitro models for assessing the interaction of MNPs with intestinal cells. Our analysis revealed that currently the majority of in vitro tests are based on the three cell lines Caco-2, HT-29, and HCT-116. They have particularly been used to assess endpoints related to basal cytotoxicity, the internalisation of MNPs and effects on the intestinal barrier. When co-cultured with various cell lines, they also allow to investigate additional effects such as inflammation, metabolic actions and the relevance of the intestinal mucus. However, methodological gaps remain regarding the assessment of a potential accumulation of MNPs, leaching of additives/impurities and in resulting long-term effects as well as cell-type specific toxicities. In addition, only few in vitro studies investigated effects of MNPs on the microbiome. Stem cell-based assays using, for example, the emerging organoid technology are promising for analysing MNP effects on tissue-like structures, while avoiding the particular characteristics of the currently used cancer derived cell lines. The various cell lines and culture techniques can be combined in testing strategies, to better elucidate potential biological interaction of MNPs with biological systems. We suggest to implement a tiered testing strategy, in which monocultures can serve as a tool for high-throughput testing of MNPs. In the next steps co-cultures can be used to assess the potential of a systemic uptake of MNPs and organ-on-a-chip models will provide more reliable insights into relevant doses triggering biological effects. Finally, organoids can help to discover new and more complex reactions initiated by MNPs.

Future perspectives for advancing regulatory science of nanotechnology-enabled health products.

The identification of regulatory challenges for nanotechnology-enabled health products, followed by discussions with the involved stakeholders, is the first step towards a strategic planning of how such challenges can be successfully addressed in the future. In order to better understand whether the identified regulatory needs are sector-specific for health products or might also hinder the progress in other domains, the REFINE consortium reached out to communities representing other sectors that also exploit the potential of nanotechnology, i.e. industrial chemicals, food and cosmetics. Through a series of trans-sectorial workshops, REFINE partners identified common as well as sector-specific challenges and discussed possible ways forward. Potential solutions lie in a more strengthen collaboration between regulatory and research communities resulting in a targeted production and exploitation of academic data for the regulatory decision-making. Furthermore, a coordinated use of knowledge sharing platforms and databases, trans-sectorial standardisation activities and harmonisation of regulatory activities between geographical regions are possible ways forward, in line with the upcoming European political initiatives such as the Chemical Strategy for Sustainability (CSS). Finally, we also discuss the perspectives for further development and sustainability of methods and tools developed in the REFINE project.

Dynamic stimulation evokes spatially focused receptive fields in bat auditory cortex.

Bats can orient and hunt for prey in complete darkness using echolocation. Due to the pulse-like character of call emission they receive a stroboscopic view of their environment. During target approach, bats adjust their emitted echolocation calls to the specific requirements of the dynamically changing environmental and behavioral context. In addition to changes of the spectro-temporal call features, the spatial focusing of the beam of the sonar emissions onto the target is a conspicuous feature during target tracking. The neural processes underlying the complex sensory-motor interactions during target tracking are not well understood. In this study, we used a two-tone-pulse paradigm with 81 combinations of inter-aural intensity differences and six inter-pulse intervals in a passive hearing task to tackle the question of how transient changes in the azimuthal position of successive sounds are encoded by neurons in the auditory cortex of the bat Phyllostomus discolor. In a population of cortical neurons (11%, 24 of 217), spatial receptive fields were focused to a small region of frontal azimuthal positions during dynamic stimulation with tone-pulse pairs at short inter-pulse intervals. The response of these neurons might be important for the behaviorally observed locking of the sonar beam onto a selected target during the later stages of target tracking. Most interestingly, the majority of these neurons (88%, 21 of 24) were located in the posterior dorsal part of the auditory cortex. This cortical subfield might thus be specifically involved in the analysis of dynamic acoustic scenes.