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Abstract Genetically-encoded dopamine (DA) sensors enable high-resolution imaging of DA release, but their ability to detect a wide range of extracellular DA levels, especially tonic versus phasic DA release, is limited by their intrinsic affinity. Here we show that a human-selective dopamine receptor positive allosteric modulator (PAM) can be used to boost sensor affinity on-demand. The PAM enhances DA detection sensitivity across experimental preparations (in vitro, ex vivo and in vivo) via one-photon or two-photon imaging. In vivo photometry-based detection of optogenetically-evoked DA release revealed that DETQ administration produces a stable 31 minutes window of potentiation without effects on animal behavior. The use of the PAM revealed region-specific and metabolic state-dependent differences in tonic DA levels and enhanced single-trial detection of behavior-evoked phasic DA release in cortex and striatum. Our chemogenetic strategy can potently and flexibly tune DA imaging sensitivity and reveal multi-modal (tonic/phasic) DA signaling across preparations and imaging approaches.

The Municipality of Venice, through Insula srl (Insula, 2024), started the RAMSES (Rilievo Altimetrico, Modellazione Spaziale E Scansione 3D) project in 2005 with the unprecedented intention of conducting a static laser scanner survey of an entire city. The authors of this paper, who have been involved in the project on behalf of the client, including drafting general contract technical specifications, wished to revisit the survey’s findings nearly two decades later. This contribution illustrates the procedures implemented to guarantee the future accessibility of the surveyed data. It is interesting to highlight how the detailed technical specifications outlined in the general technical contract section have facilitated the retrieval of the historical three-dimensional laser scanner measurements archive. Tests have been conducted to determine how the existing mobile mapping technologies may be utilised to update the three-dimensional historical data obtained in the Ramses project efficiently. Furthermore, the paper describes the surveying approach that has never been adequately described in the literature. The surveying and geo-referencing methodologies continue to have several interesting and relevant aspects, especially regarding how the topographic network has been implemented. The Ramses three-dimensional model represents an extraordinary, valuable digital archive containing portraits of the city’s conditions at the time of the mapping. Ramses 3D model, when enriched with field activities conducted using more updated technologies, can provide interesting and unique evaluations of the evolution of Venice’s landscape.

Abstract The bronze doors of the Basilica of San Zeno in Verona, Italy, are a special case in art history research. They were made by several workshops during the twelfth century: stylistically, two to three workshops were assumed to produce the metal parts of the door. However, it is still unclear when exactly and if this interpretation can be supported by the chemical composition of the metal. In this research we aimed to verify the art history interpretation by identifying the alloy composition of each individual metal plate. The composition of the supporting wooden structures are discussed. A portable ED-XRF instrument and optical microscopes were used to analyse and document the doors non-invasively. The doors were also photographed to produce high resolution orthophotos and 3D models. We can confirm that the metal parts of the doors were made of leaded tin-bronze as well as leaded brass and mounted on a wooden structure mainly made of spruce and oak wood. Chemically, two/three different groups of alloys have been identified, which can be associated with two or three different workshops, and which largely correspond to the stylistic interpretation.

IntroductionIn this study we explore how the diagnostic category of mood disorders is constructed in two handbooks of Psychopathology as an example of the mainstream construction of psychopathology. Despite the increasing criticism and lack of evidence, the debunked chemical imbalance theory of the etiology of depression still dominates the professional and pop/folk understanding and interventions.MethodsWe analysed the breadth of the inference field and the type of etiopathogenetic contents of the explanations of mood disorders using the “1to3” Coding System.ResultsOur findings show that the dominant explanations draw almost exclusively onto monadic explanations, followed by limited dyadic ones. Intrapersonal etiopathogenetic contents prevailed, and biomedical explanations were dominant in both textbooks.DiscussionWe critically discuss the underpinnings of these results and address the clinical implications of these biased representations, as well as potential alternative approaches to psychopathology.

Used as a communicative tool for risk management, risk maps provide a service to the public, conveying information that can raise risk awareness and encourage mitigation. Several studies have utilized risk maps to determine risks associated with the distribution of Borrelia burgdorferi, the causal agent of Lyme disease in North America and Europe, as this zoonotic disease can lead to severe symptoms. This literature review focused on the use of risk maps to model distributions of B. burgdorferi and its vector, the blacklegged tick (Ixodes scapularis), in North America to compare variables used to predict these spatial models. Data were compiled from the existing literature to determine which ecological, environmental, and anthropic (i.e., human focused) variables past research has considered influential to the risk level for Lyme disease. The frequency of these variables was examined and analyzed via a non-metric multidimensional scaling analysis to compare different map elements that may categorize the risk models performed. Environmental variables were found to be the most frequently used in risk spatial models, particularly temperature. It was found that there was a significantly dissimilar distribution of variables used within map elements across studies: Map Type, Map Distributions, and Map Scale. Within these map elements, few anthropic variables were considered, particularly in studies that modeled future risk, despite the objective of these models directly or indirectly focusing on public health intervention. Without including human-related factors considering these variables within risk map models, it is difficult to determine how reliable these risk maps truly are. Future researchers may be persuaded to improve disease risk models by taking this into consideration.

B cell clonal expansion and cerebrospinal fluid (CSF) oligoclonal IgG bands are established features of the immune response in multiple sclerosis (MS). Clone-specific recombinant monoclonal IgG1 Abs (rAbs) derived from MS patient CSF plasmablasts bound to conformational proteolipid protein 1 (PLP1) membrane complexes and, when injected into mouse brain with human complement, recapitulated histologic features of MS pathology: oligodendrocyte cell loss, complement deposition, and CD68+ phagocyte infiltration. Conformational PLP1 membrane epitopes were complex and governed by the local cholesterol and glycolipid microenvironment. Abs against conformational PLP1 membrane complexes targeted multiple surface epitopes, were enriched within the CSF compartment, and were detected in most MS patients, but not in inflammatory and noninflammatory neurologic controls. CSF PLP1 complex Abs provide a pathogenic autoantibody biomarker specific for MS.

Abstract There is a contemporary trend in many major research institutions to de‐emphasize the importance of natural history education in favor of theoretical, laboratory, or simulation‐based research programs. This may take the form of removing biodiversity and field courses from the curriculum and the sometimes subtle maligning of natural history research as a “lesser” branch of science. Additional threats include massive funding cuts to natural history museums and the maintenance of their collections, the extirpation of taxonomists across disciplines, and a critical under‐appreciation of the role that natural history data (and other forms of observational data, including Indigenous knowledge) play in the scientific process. In this paper, we demonstrate that natural history knowledge is integral to any competitive science program through a comprehensive review of the ways in which they continue to shape modern theory and the public perception of science. We do so by reviewing how natural history research has guided the disciplines of ecology, evolution, and conservation and how natural history data are crucial for effective education programs and public policy. We underscore these insights with contemporary case studies, including: how understanding the dynamics of evolutionary radiation relies on natural history data; methods for extracting novel data from museum specimens; insights provided by multi‐decade natural history programs; and how natural history is the most logical venue for creating an informed and scientifically literate society. We conclude with recommendations aimed at students, university faculty, and administrators for integrating and supporting natural history in their mandates. Fundamentally, we are all interested in understanding the natural world, but we can often fall into the habit of abstracting our research away from its natural contexts and complexities. Doing so risks losing sight of entire vistas of new questions and insights in favor of an over‐emphasis on simulated or overly controlled studies.

Musculoskeletal complaints are one cornerstone of urgent issues for which orthopedic and emergency physicians provide care. Ultrasound can be a useful diagnostic tool to help identify musculoskeletal injuries. We describe a case of bilateral patellar tendon rupture that presented after minor trauma, and had the diagnosis confirmed at the bedside by point-of-care ultrasound.Physicians caring for patients with orthopedic injuries should be familiar with the use of ultrasound to diagnose tendon ruptures.

IntroductionIn the tradition of phenomenological psychiatry, schizophrenia is described as a disturbance of the minimal self, i.e. the most basic form of self-awareness. This disturbance of the minimal self at the individual level is assumed to precede the intersubjective disturbances such as boundary weakening. However, the role of intersubjective disturbances in the emergence and recovery of schizophrenic experience still remains an open question. This phenomenological study focuses on how encounters with others shape self-experience during from psychosis by analyzing this process from the perspective of cultural differences, which in current research is especially under-researched. While most phenomenological accounts are based on first person-accounts from Western, individualist cultures where the self is conceived and experienced as separate to others, the present study qualitatively investigates psychotic experiences of patients from Jaffna, Sri Lanka.MethodSemi-structured interviews were conducted with three participants with a diagnosis of schizophrenia or first episode psychosis. The interviews were transcribed and analyzed using interpretative phenomenological analysis (IPA). Eight group experiential themes were identified across interviews.ResultsThe data suggest that intersubjective processes of boundary weakening such as invasiveness and hyperattunement may shape minimal self-experience and more specifically contribute to a mistrust of the own senses and to hyper-reflexivity. Interestingly, boundary weakening yields pervasive emotions and can be experienced as a threat to the whole social unit. On the one hand, the strengthening of self-other-boundary was achieved through opposition, closedness and withdrawal from others. On the other hand, this study suggests that the re-opening of self-other-boundaries in response to the crisis may help establish connectedness and may lead to recovery.

Abstract We explore the connections between crustal shortening, volcanism, and mantle dynamics in the Atlas of Morocco. In response to compressional forces and strain localization, this intraplate orogen has evolved far from convergent plate margins. Convective effects, such as lithospheric weakening and plume‐related volcanism, contributed in important ways to the building of high topography. We seek to better understand how crustal and mantle processes interacted during the Atlas' orogeny by combining multiple strands of observations, including new and published data. Constraints on crustal and thermal evolution are combined with new analyses of topographic evolution, petrological, and geochemical data from the Anti‐Atlas volcanic fields, and a simple numerical model of the interactions among crustal deformation, a mantle plume, and volcanism. Our findings substantiate that: (a) crustal deformation and exhumation accelerated during the middle/late Miocene, contemporaneous with the onset of volcanism; (b) volcanism has an anorogenic signature with a deep source; (c) a dynamic mantle upwelling supports the high topography. We propose that a mantle plume and the related volcanism weakened the lithosphere beneath the Atlas and that this favored the localization of crustal shortening along pre‐existing structures during plate convergence. This convective‐tectonic sequence may represent a general mechanism for the modification of continental plates throughout the thermo‐chemical evolution of the supercontinental cycle.

Abstract Two-photon fluorescence calcium imaging allows recording the activity of large neural populations with subcellular spatial resolution, but it is typically characterized by low signal-to-noise ratio (SNR) and poor accuracy in detecting single or few action potentials when large number of neurons are imaged. We recently showed that implementing a smart line scanning approach using trajectories that optimally sample the regions of interest increases both the SNR fluorescence signals and the accuracy of single spike detection in population imaging in vivo. However, smart line scanning requires highly specialised software to design recording trajectories, interface with acquisition hardware, and efficiently process acquired data. Furthermore, smart line scanning needs optimized strategies to cope with movement artefacts and neuropil contamination. Here, we develop and validate SmaRT2P, an open-source, user-friendly and easy-to-interface Matlab-based software environment to perform optimized smart line scanning in two-photon calcium imaging experiments. SmaRT2P is designed to interface with popular acquisition software (e.g., ScanImage) and implements novel strategies to detect motion artefacts, estimate neuropil contamination, and minimize their impact on functional signals extracted from neuronal population imaging. SmaRT2P is structured in a modular way to allow flexibility in the processing pipeline, requiring minimal user intervention in parameter setting. The use of SmaRT2P for smart line scanning has the potential to facilitate the functional investigation of large neuronal populations with increased SNR and accuracy in detecting the discharge of single and few action potentials.

Processing of two-photon calcium imaging data is generally time-consuming, especially for large fields of view. Here, the authors present CITE-On, a tool based on a convolutional neural network, enabling online automatic cell identification, segmentation, identity tracking, and trace extraction.

Thirty-one alpine species of Cortinarius (Agaricales, Cortinariaceae) were described from the alpine zone of the Alps during the second half of the XX century, by the Swiss mycologist Jules Favre, and by the French mycologists Denise Lamoure and Marcel Bon. Notoriously difficult to identify by macro- and microscopical characters, most of these species, which belong to subgen. Telamonia, have been thoroughly revised in global publications based on type sequencing. Recent surveys in the alpine areas of France (Savoie) and Italy (Lombardy), as well as the sequencing of D. Lamoure’s collections, identified three new species that are here described and illustrated: C. dryadophilus in sect. Castanei, C. infidus in sect. Verni, and C. saniosopygmaeus in sect. Saniosi. The holotypes of C. caesionigrellus Lamoure and C. paleifer var. brachyspermus Lamoure could be sequenced. A recent collection of the former is described and illustrated here for the first time, and based on available data, the latter name is recombined as Cortinarius flexipes var. brachyspermus comb. nov. Lastly, C. argenteolilacinus var. dovrensis is reported from the alpine zone for the first time and a new combination, Thaxterogaster dovrensis comb. & stat. nov. is introduced in the present work.

Telephone helplines offer a valued service for those in distress. However, little research has explored the experience of helpline volunteers. Through semi-structured interviews, we explore the volunteering experiences of nine long-term UK Samaritan volunteers. Interviews were analysed using Interpretive Interactionism. The analysis highlighted that volunteering impacted participants' experience of their sense of self. The decision to volunteer was framed as part of a search for personal meaning, tied to experiences of loss and reparation. Participants reflected positively on their volunteer identity, but highlighted tensions between a sense of vocation and the experience of care burden. The Samaritan Community also offered a sense of belonging and social support. They experienced involvement as personally meaningful, enabling the construction of a positive self-identity.

Tsunamis are devastating events. They are especially difficult to predict, when generated by landslides. In this paper, the authors overcome this issue by modelling the landslide and the tsunami in a unified framework in unprecedented detail.

Analysis of new detrital apatite fission-track (AFT) ages from modern river sands, published bedrock and detrital AFT ages, and bedrock apatite (U-Th)/He (AHe) ages from the Northern Apennines provides new insights into the spatial and temporal patterns of erosion rates through time across the orogen. The pattern of time-averaged erosion rates derived from AHe ages from the Ligurian side of the orogen illustrates slower erosion rates relative to AFT rates from the Ligurian side and relative to AHe rates from the Adriatic side. These results are corroborated by an analysis of paired AFT and AHe thermochronometer samples, which illustrate that erosion rates have generally increased through time on the Adriatic side but have decreased through time on the Ligurian side. Using an updated kinematic model of an asymmetric orogenic wedge, with imposed erosion rates on the Ligurian side that are a factor of 2 slower relative to the Adriatic side, we demonstrate that cooling ages and maximum burial depths are able to replicate the pattern of measured cooling ages across the orogen and estimates of burial depth from vitrinite reflectance data. These results suggest that horizontal motion is an important component of the overall rock motion in the wedge, and that the asymmetry of the orogen has existed for at least several million years.

Mothers are viewed as the people who are raising future citizens of Canada; therefore, their parenting practices are being targeted for intervention by civic organizations funded by the state. In this article, I argue that modernity narratives and neoliberalism approaches to mothering inform parenting education classes for Somali refugee women to Canada. Thus, Somali women are often seen as victims. Stereotyped identities conceal their social and historical agency. This research draws on 15 individual interviews with Somali mothers and participant- observation in two parenting education classes in Canada.

The Ludoialm landslide, which is located in the municipality of Münster in Tyrol, Austria, represents a large-scale translational landslide in glacial soil sediments characterised by an exceptionally low inclined basal shear zone of only 12°. Although a temporal coincidence between meteorological events and slope displacement is obvious, the hydromechanical coupled processes responsible for the initial landslide formation and the ongoing movement characteristics have not yet been identified. This article provides a comprehensive analysis of the predisposition factors and the initial failure mechanism of this landslide from geological and geotechnical perspectives. We use a prefailure geometry of the cross section to simulate the initial slope failure process by a limit equilibrium analysis (LEA), a strength-reduction finite element method (SRFEM), and a finite element limit analysis (FELA). The shape and location of the computationally obtained basal sliding zone compare well with the geologically assumed one. Based on the computational study, it turns out that a high groundwater table probably caused by snow melting in combination with different permeabilities for the different layers is needed for the formation of the exceptionally low inclined basal shear zone. This paper presents the failure mechanism of the Ludoialm landslide and discusses the role of the shear band propagation in the process of slope destabilization.

Phenomenological psychopathology focuses on the first-person experience of mental disorders. Although it is in principle descriptive, it also entails an explanatory dimension: single psychological symptoms are conceived as genetically arising from a holistic structure of personal experience, i.e., the patient's being-in-the-world – and of its dynamic unfolding over time. Yet both classical and current phenomenological approaches tend to identify the essential disorder or “trouble générateur” (Minkowski) of mental illness within the individual, thereby neglecting the relevance of the social context not only for the emergence of symptoms but also for their treatment. The work of Wolfgang Blankenburg on schizophrenia represents a noteworthy approach to overcome this individualistic tendency. He introduced the concept of “loss of common sense” as the structural core of schizophrenic experience and being-in-the-world and he considered the social and most importantly familial context for the emergence of schizophrenic experience. By accounting not only for personal experience but also for interactional structures of families and social milieus in which experience is embedded, Blankenburg thereby offered ways to combine phenomenological and systemic explanations of mental disorders. Beside his most renowned work on “the loss of common sense,” in this paper we also present his family studies of young persons with schizophrenia, which have so far received little if no attention. We thus discuss the different ways in which Blankenburg expanded the phenomenological approach into a more systemic and social direction. We then link Blankenburg's work with current systemic explanatory models of schizophrenia and explore the clinical and scientific implications of this link. Finally, we call for further research on the synergy effects between the two.

The brown marmorated stink bug, Halyomorpha halys, is a pentatomid bug of Eastern Asian origin that became an economically relevant pest in the Eurasian and American continents. Management of this species is limited to use of chemical insecticides: an inefficient method due to the strong adaptability of the target pest. The sterile insect technique (SIT) is potentially a valid tactic in the search for nontoxic alternatives. In this work, we investigated the suitability of mass-trapped overwintering males, collected during the aggregation phase before the winter diapause, for their release as competitive sterile males in an SIT programme. Differently from previous studies, irradiation was applied with a linear accelerator device that produced high-energy photons. Following a similar scientific protocol with newly emerged irradiated males, the effects of X-ray irradiation on physiological parameters (longevity, fecundity and fertility) were assessed. In addition, behavioural bioassays were carried out in no-choice conditions to evaluate if irradiation interferes with mating processes. The results are very encouraging; the effects of the irradiation at 32 Gy did not differ from the controls in the longevity or fecundity of the exposed overwintering adults. The hatching rate of the eggs laid by the fertile females that had mated with the irradiated males was less than 5%. The results of behavioural bioassays showed that the irradiation did not cause a significant impact on the quality of the sterile males. More research is warranted to evaluate the mating competitiveness of sterile males in semi-field and field conditions.

Some 20 Myr after the Late Jurassic to Early Cretaceous obduction and collision at the eastern margin of Adria, the eroded Pelagonia (Adria)–Axios/Vardar (oceanic complex) contact collapsed, forming the Kallipetra Basin, described around the Aliakmon River near Veroia (northern Greece). Clastic and carbonate marine sediments deposited from the early Cenomanian to the end of the Turonian, with abundant olistoliths and slope failures at the base due to active normal faults. The middle part of the series is characterized by red and green pelagic limestones, with a minimal contribution of terrigenous debris. Rudist mounds in the upper part of the basin started forming on the southwestern slope, and their growth competed with a flux of ophiolitic debris, documenting the new fault scarps affecting the Vardar oceanic complex (VOC). Eventually, the basin was closed by overthrusting of the VOC towards the northeast and was buried and heated up to ∼ 180 ∘C. A strong reverse geothermal gradient with temperatures increasing up-section to near 300 ∘C is recorded beneath the VOC by illite crystallinity and by the crystallization of chlorite during deformation. This syntectonic heat partially reset the zircon fission track ages bracketing the timing of closure just after the deposition of the ophiolitic debris in the Turonian. This study documents the reworking of the Pelagonian–Axios/Vardar contact, with Cenomanian extension and basin widening followed by Turonian compression and basin inversion. Thrusting occurred earlier than previously reported in the literature for the eastern Adria and shows a vergence toward the northeast, at odds with the regional southwest vergence of the whole margin but in accordance to some reports about 50 km north.

Calcium dynamics into astrocytes influence the activity of nearby neuronal structures. However, because previous reports show that astrocytic calcium signals largely mirror neighboring neuronal activity, current information coding models neglect astrocytes. Using simultaneous two-photon calcium imaging of astrocytes and neurons in the hippocampus of mice navigating a virtual environment, we demonstrate that astrocytic calcium signals encode (i.e., statistically reflect) spatial information that could not be explained by visual cue information. Calcium events carrying spatial information occurred in topographically organized astrocytic subregions. Importantly, astrocytes encoded spatial information that was complementary and synergistic to that carried by neurons, improving spatial position decoding when astrocytic signals were considered alongside neuronal ones. These results suggest that the complementary place dependence of localized astrocytic calcium signals may regulate clusters of nearby synapses, enabling dynamic, context-dependent variations in population coding within brain circuits.

The dilatancy/contractancy of soil is of particular importance for compaction, consolidation, liquefaction, etc. Interestingly, constitutive relations are often unsatisfactory in modelling volume changes in the sense that their predictions deviate considerably from each other. This scatter is pronounced in problems with stress rotation. Therefore, in this paper some selected constitutive relations are investigated with respect to their performance at stress rotation. The obtained numerical simulations are compared to each other and also with experimental results from the 1γ2ε and the hollow cylinder apparatuses.

Medical adhesives are used to secure wound care dressings and other critical devices to the skin. Without means of safe removal, these stronger adhesives are difficult to painlessly remove from the skin and may cause medical-adhesive-related skin injuries (MARSI), including skin tears and an increased risk of infection. Lower-adhesion medical tapes may be applied to avoid MARSI, leading to device dislodgement and further medical complications. This paper outlines the development of a high-adhesion medical tape designed for low skin trauma upon release. By warming the skin-attached tape for 10–30 s, a significant loss in adhesion was achieved. A C14/C18 copolymer was developed and combined with a selected pressure-sensitive adhesive (PSA) material. The addition of 1% C14/C18 copolymer yielded the largest temperature-responsive drop in surface adhesion. The adhesive film was characterized using AFM, and distinct nanodomains were identified on the exterior surface of the PSA. Our optimized formulation yielded 67% drop in adhesion when warmed to 45 °C, perhaps due to melting nanodomains weakening the adhesive–substrate boundary layer. Pilot clinical testing resulted in a significant decrease in pain when a heat pack was used for removal, giving an average pain reduction of 66%.

Raponzolo is a paleo-phreatic cave explored in 2011 in the Brenta Dolomites (Trentino, Italy), at the remarkable altitude of 2,560 m a.s.l. Differently to all other caves of the area, it hosts well-cemented fine to medium sands of granitic-metamorphic composition. The composition suggests a sediment source from the Adamello and Tonale Unit, separated from the Brenta by one of the most important tectonic lineaments of the Alps (Giudicarie Line). The fine-sand sediment was sampled to determine burial time and thus a minimum age of the cave. Cosmogenic isotopes (26Al and 10Be) in quartz grains allowed to estimate a minimum burial age of 5.25 Ma based on the mean sediment transport time at the surface and infer original altitude of the catchment area. Detrital apatite fission-track (AFT) and U-Pb dating on zircons provide information on the source, both from a regional and altitude (exhumation) perspective. Two populations of detrital AFT ages center at 17 (−2.3 + 2.6) Ma and 23 (−3.3 + 3.9) Ma, whereas the main detrital zircon U-Pb age populations are younger than 40 Ma. These correspond to intrusive and metamorphic sources nowadays outcropping exclusively above 2,200–2,300 m a.s.l. in Northern Adamello and Tonale. The results point to a late Miocene erosion and infilling of the cave by allochtonous sediments, with important implications on the timing of cave speleogenesis, as well as the paleogeographical connection, tectonic evolution and uplift of different structural units of the Alps. The roundness and the well sorted size of the quartz grains suggest a fluvial or aeolian origin, possibly recycled by glacial activity related to cold events reported in high latitude areas of the world at 5.75 and 5.51 Ma. These glacial phases have never been documented before in the Alps. This information confirms that the valleys dividing these geological units were not yet deeply entrenched during the onset of the Messinian Salinity Crisis (5.6–5.5 Ma), allowing an efficient transport of sediments across major tectonic lineaments of the Alps. This study shows the potential of cave sediments to provide information not only on the age of speleogenesis but also on the paleogeography of a wide area of the Alps during the late Miocene.

All-optical methods for imaging and manipulating brain networks with high spatial resolution are fundamental to study how neuronal ensembles drive behavior. Stimulation of neuronal ensembles using two-photon holographic techniques requires high-sensitivity actuators to avoid photodamage and heating. Moreover, two-photon-excitable opsins should be insensitive to light at wavelengths used for imaging. To achieve this goal, we developed a novel soma-targeted variant of the large-conductance blue-light-sensitive opsin CoChR (stCoChR). In the mouse cortex in vivo, we combined holographic two-photon stimulation of stCoChR with an amplified laser tuned at the opsin absorption peak and two-photon imaging of the red-shifted indicator jRCaMP1a. Compared to previously characterized blue-light-sensitive soma-targeted opsins in vivo, stCoChR allowed neuronal stimulation with more than 10-fold lower average power and no spectral crosstalk. The combination of stCoChR, tuned amplified laser stimulation, and red-shifted functional indicators promises to be a powerful tool for large-scale interrogation of neural networks in the intact brain.

Embryonic taste bud primordia are specified as taste placodes on the tongue surface and differentiate into the first taste receptor cells (TRCs) at birth. Throughout adult life, TRCs are continually regenerated from epithelial progenitors. Sonic hedgehog (SHH) signaling regulates TRC development and renewal, repressing taste fate embryonically, but promoting TRC differentiation in adults. Here, using mouse models, we show TRC renewal initiates at birth and coincides with onset of SHHs pro-taste function. Using transcriptional profiling to explore molecular regulators of renewal, we identified Foxa1 and Foxa2 as potential SHH target genes in lingual progenitors at birth and show that SHH overexpression in vivo alters FoxA1 and FoxA2 expression relevant to taste buds. We further bioinformatically identify genes relevant to cell adhesion and cell locomotion likely regulated by FOXA1;FOXA2 and show that expression of these candidates is also altered by forced SHH expression. We present a new model where SHH promotes TRC differentiation by regulating changes in epithelial cell adhesion and migration.

The electroencephalogram (EEG) is a major tool for non-invasively studying brain function and dysfunction. Comparing experimentally recorded EEGs with neural network models is important to better interpret EEGs in terms of neural mechanisms. Most current neural network models use networks of simple point neurons. They capture important properties of cortical dynamics, and are numerically or analytically tractable. However, point neurons cannot generate an EEG, as EEG generation requires spatially separated transmembrane currents. Here, we explored how to compute an accurate approximation of a rodent's EEG with quantities defined in point-neuron network models. We constructed different approximations (or proxies) of the EEG signal that can be computed from networks of leaky integrate-and-fire (LIF) point neurons, such as firing rates, membrane potentials, and combinations of synaptic currents. We then evaluated how well each proxy reconstructed a ground-truth EEG obtained when the synaptic currents of the LIF model network were fed into a three-dimensional network model of multicompartmental neurons with realistic morphologies. Proxies based on linear combinations of AMPA and GABA currents performed better than proxies based on firing rates or membrane potentials. A new class of proxies, based on an optimized linear combination of time-shifted AMPA and GABA currents, provided the most accurate estimate of the EEG over a wide range of network states. The new linear proxies explained 85-95% of the variance of the ground-truth EEG for a wide range of network configurations including different cell morphologies, distributions of presynaptic inputs, positions of the recording electrode, and spatial extensions of the network. Non-linear EEG proxies using a convolutional neural network (CNN) on synaptic currents increased proxy performance by a further 2-8%. Our proxies can be used to easily calculate a biologically realistic EEG signal directly from point-neuron simulations thus facilitating a quantitative comparison between computational models and experimental EEG recordings.