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Berger, J.

Publications and source records attributed to Berger, J..

At least 19 recordsLinked to original sources

Use of the Elston-Stewart algorithm for the efficient calculation of exact pedigree-based Y-STR match probabilities

The formal assessment of a genetic match between a suspect and some biological trace material is one of the key tasks of forensic genetics, particularly in cases of sexual offence. The analysis of Y-chromosomal short tandem repeats (Y-STRs) has proven especially useful in this context. For a long time, however, calculating the probability of a perfect Y-STR profile match under the defense hypothesis that the suspect was not the trace donor posed a great challenge. This was due to the inherent uncertainty about the population of alternative donors, the so-called suspect population. We recently proposed to resolve this controversy by systematically favoring the suspect and considering his close male relatives as the suspect population. However, since the mathematical framework developed for this purpose was simulation-based, its practical application turned out increasingly difficult with increasing pedigree size. Here, we present an adaptation of the so-called Elston-Stewart algorithm, originally developed for the linkage analysis of human genetic diseases, to allow calculation of exact match probabilities in a time that scales linearly with pedigree size. The adapted algorithm was implemented in a publicly available software tool, and its correctness was verified by the comparison of its output with the correct, analytical results obtained for selected example pedigrees. The new implementation mostly outperforms the simulation-based solution, albeit with the important exception of Y-STRs present in multiple copies. Given the increasingly prominent role of such multicopy markers in forensic genetics, the complementary use of both approaches appears the most sensible strategy for the time being.

genetics↗

Beyond the surface: plasmalogens are dispensable for retinal integrity and fertility in the mouse

Ether lipids and their subclass, the plasmalogens, are critical regulators of membrane organization, signaling, and stress responses in multiple tissues. Inborn errors in their anabolism cause severe multi-organ diseases such as Rhizomelic Chondrodysplasia Punctata and related peroxisomal disorders. The Gnpat knockout mouse model, characterized by total ether lipid deficiency, recapitulates key features of this disorder, including dense bilateral cataracts, microphthalmia, and infertility, but the specific contribution of different subclasses like plasmalogens remains elusive. The recent identification of the Peds1 gene allows dissecting the impact of selective plasmalogen deficiency with retention of plasmanyl lipids, another ether lipid subgroup. Here, we performed the first side-by-side comparison of Gnpat and Peds1 knockout in mice on a matched genetic background (C57BL/6 x CD1). In contrast to the situation in Gnpat knockout mice, plasmanyl lipids in Peds1 knockout mice were sufficient to prevent cataract formation and maintain normal ocular structures, despite marked shifts in the ocular phospholipidome. Also, fertility and reproductive function were found to be preserved in Peds1 knockout mice. Our data demonstrate that plasmanyl lipids can partially protect against the severe phenotypes observed in mouse models of total ether lipid deficiency; notably, the ocular and reproductive phenotypes were plasmalogen-independent, indicating that loss of the vinyl ether double bond is not the key determinant of all symptoms in human and murine ether lipid deficiency and can at least partly be compensated by plasmanyl lipids. HighlightsO_LIIn mice, total ether lipid deficiency causes cataracts and infertility. C_LIO_LIThe role of plasmalogens in these phenomena remains unclear. C_LIO_LITwo PEDS1-deficient patients were reported, but cataracts were observed in only one case. C_LIO_LIPeds1-deficient mice have no cataracts or ocular abnormalities. C_LIO_LIMice with a deletion of Peds1 display normal fertility rates. C_LI

biochemistry↗

How does individual trait variation impact the survival of populations with an Allee effect?

The Allee effect is a phenomenon where individual fitness is reduced in small populations, for example because of mate-finding difficulties or increased predation. Allee effects matter in conservation biology because they can drive small populations to extinction. The severity of Allee effects can depend on traits such as mate-search rate and defense against predators. Many natural populations exhibit considerable intraspecific trait variation (ITV) in such traits, but most studies so far assume these traits to be constant. Thus the impact of ITV on populations with Allee effect is largely unknown. Here we create two individual-based stochastic models that simulate a small population experiencing either a mate-finding Allee effect or a predator-driven Allee effect. We analyze how ITV, trait inheritance, and mutation affect the proportion of surviving populations. Under the mate-finding Allee effect, higher ITV hindered population survival and increased Allee thresholds. This can be explained by Jensens inequality and the negative curvature of the mate-finding function. Under the predator-driven Allee effect, ITV effects were weak, but higher mutation standard deviations were beneficial, likely because they provided more substrate for selection to act on. We thus recommend to take into account ITV when dealing with threatened populations with an Allee effect.

ecology↗

Optically detected and radio wave-controlled spin chemistry in cryptochrome

Optically addressable spin systems, such as nitrogen-vacancy centers in diamond, have been widely studied for quantum sensing applications. In this work, we demonstrate that certain flavoproteins -- specifically cryptochrome and iLOV -- which generate spin correlated radical pairs upon optical excitation, also exhibit optically detected magnetic resonance (ODMR). Remarkably, the iLOV protein, commonly used in cellular imaging, displays ODMR contrast approaching 50%. We present initial applications including widefield magnetic field sensing and spatial modulation of photoluminescence using radiofrequency pulses and magnetic field gradients. Our results establish radical pairs in proteins as a novel platform for optically addressable spin systems, offering the key advantages of molecular designability and genetic encodability. Moreover, due to the spin-selective nature of radical pair chemistry, the results lay the groundwork for future radiofrequency-based manipulation of biological systems.

biophysics↗

Cryptocercus genomes expand knowledge of adaptations to xylophagy and termite sociality

Subsociality and wood-eating or xylophagy are understood as key drivers in the evolution of eusociality in Blattodea (cockroaches and termites), two features observed in the cockroach genus Cryptocercus, the sister group of all termites. We present and analyse two new high-quality genomes from this genus, C. punctulatus from North America and C. meridianus from Southeast Asia, to explore the evolutionary transitions to xylophagy and subsociality within Blattodea. Our analyses reveal evidence of relaxed selection in both Cryptocercus and termites, indicating that a reduction in effective population size may have occurred in their subsocial ancestors. These findings challenge the expected positive correlation between dN/dS ratios and social complexity, as Cryptocercus exhibits elevated dN/dS values that may exceed those of eusocial termites. Additionally, we identify positive selection on mitochondrial ribosomal proteins and components of the NADH dehydrogenase complex, suggesting significant evolutionary changes in energy production. Future studies incorporating additional genomic data from diverse blattodean species are essential to elucidate the molecular mechanisms driving transitions to xylophagy and eusociality.

evolutionary biology↗

Reduced regulatory complexity associated with the evolutionary transition to sociality from cockroaches to termites despite evolutionary parallels with Hymenoptera

The degree of phenotypic diversity within social species has previously been associated with more complex genetic regulation both in cis and trans contexts. Transcription factors (TFs) being key to genetic regulation, have been studied in the origins of eusociality in Hymenoptera (bees, ants and wasps) but less so in Blattodea (cockroaches and termites). Here we show that the social transition in Blattodea, from cockroaches to termites, displays similar patterns of regulatory change to those found in Hymenoptera. Specifically, by analysing 3 cockroach and 5 termite genomes, we find more TF families with relaxed selection compared to intensified selection and lineage-specific gene family expansions in termites, which has also been reported in Hymenoptera. We also find that genes under selection support neotenic caste determination. We find there are key differences in Blattodea TF regulation in comparison with Hymenoptera with contractions in TF gene families and no compensatory change in TF DNA binding motifs either in frequency or diversity in TF promoter regions. Furthermore, we show that an increase in social complexity leads to greater diversity in TF activating domains, one of the evolutionary and structural building blocks of TFs, meanwhile, DNA-binding domains, undergo very little change. This study highlights similarities in social transitions between Hymenoptera and Blattodea, with evidence of large changes in transcriptional regulation followed by lineage specific adaptations. Our results indicate that the transcriptional diversity linked to social complexity is not attributable to transcription factors, but is instead likely driven by an alternative mechanism.. Significance statementIt has been widely reported that increased phenotypic complexity, particularly arising from social transitions, is often accompanied by increased regulatory complexity followed by lineage-specific adaptations. While extensively studied in Hymenoptera (bees, ants, and wasps), it has been less explored in Blattodea (cockroaches and termites). By examining the evolution of transcription factors across Blattodea, we investigated the regulatory changes associated with this social transition. Our study reveals that increased social complexity in Blattodea is accompanied by a reduction in regulatory complexity, including decreases in transcription factor numbers and no compensatory change in TF promoter binding site diversity or regulation. This study highlights that social transitions in Blattodea and Hymenoptera share a common pattern of large regulatory changes followed by lineage-specific adaptations.

evolutionary biology↗

An active model for the basilar membrane and the outer hair cells

A model for the joint motion of the basilar membrane (BM) and the outer hair cells (OHC) in the cochlea is presented. The model consists of two one-dimensional mass distributions, one along the OHC and outer hair bundle (OHB) interface, and one along the BM. The motion of these masses is driven by the forces exerted on them by the elastic bodies connecting them and by the pressure difference in the fluids separated by the BM. The model includes a nonlinear motility of the OHC and its coupling with the vibrations of the BM. The model implies a Hopf bifurcation for the dynamical system governing the two coupled distributed oscillators. It is shown that when the system operates near the bifurcation point the BM motion is amplified up to a saturation level. The model provides very sharp frequency decomposition of the incident audio signal according to the place principle. It also acts as a powerful filter that distinguishes pure tones even in the presence of louder noisy background. In addition to simulations of the model, the unusual role played by the OHC friction is studied. Energy estimates are derived for the model functions.

physiology↗

Identification of unique and potent inhibitors of SARS-CoV-2 main protease from DNA-encoded chemical libraries

In vitro screening of large compounds libraries with automated high-throughput screening is expensive, time consuming and requires dedicated infrastructures. Conversely, the selection of DNA-encoded chemical libraries (DECL) can be rapidly performed with routine equipment available in most laboratories. In this study we identified novel inhibitors of SARS-CoV-2 main protease (Mpro) through the affinity-based selection of the DELopen library (open access for academics), containing 4.2 billion compounds. The identified inhibitors were peptide-like compounds containing an N-terminal electrophilic group able to form a covalent bond with the nucleophilic Cys145 of Mpro, as confirmed by x-ray crystallography. This DECL selection campaign enabled the discovery of the unoptimized compound SLL11 displaying an IC50 of 30 nM, proving that the rapid exploration of large chemical spaces enabled by DECL technology, allows for the direct identification of potent inhibitors avoiding several rounds of iterative medicinal chemistry. Compound MP1, a close analogue of SLL11, showed antiviral activity against SARS-CoV-2 in the low micromolar range when tested in Caco-2 and Calu-3 (EC50 = 2.3 {micro}M) cell lines. As peptide-like compounds can suffer from low cell permeability and metabolic stability, the cyclization of the compounds as well as the substitution of selected residues with D-enantiomers will be explored in the future to improve the antiviral activity of these novel compounds.

microbiology↗

Osteocalcin of maternal and embryonic origins synergize to establish homeostasis in offspring

Many physiological functions regulated by osteocalcin are affected in adult offspring of mothers experiencing an unhealthy pregnancy. Furthermore, osteocalcin signaling during gestation influences cognition and adrenal steroidogenesis in adult mice. Together these observations suggest that osteocalcin functions during pregnancy may be a broader determinant of organismal homeostasis in adult mammals than previously thought. To test this hypothesis, we analyzed in unchallenged wildtype and Osteocalcin-deficient, newborn, and adult mice of various genotypes and origin, and that were maintained on different genetic backgrounds, the functions of osteocalcin in the pancreas, liver and testes and their molecular underpinnings. This analysis revealed that providing mothers are themselves Osteocalcin-deficient, Osteocalcin haploinsufficiency in embryos hampers insulin secretion, liver gluconeogenesis, glucose homeostasis, testes steroidogenesis in adult offspring; inhibits cell proliferation in developing pancreatic islets and testes; and disrupts distinct programs of gene expression in these organs and in the brain. This study indicates that through their synergistic regulation of multiple physiological functions, osteocalcin ofmaternal and embryonic origins contributes to the establishment and maintenance of organismal homeostasis in newborn and adult offspring.

physiology↗

SPAG6 promotes cell migration and induces epithelial-to-mesenchymal transition in luminal breast cancer cells

Understanding the involvement of promoter DNA methylation changes in the development of breast cancer may be highly informative for designing more effective therapeutic treatments. We recently characterized the Sperm Associated Antigen 6 (SPAG6) gene, encoding a flagellar motility protein, as a potential DNA methylation biomarker for blood-based early breast cancer detection. Here we present the first study to evaluate the functional role of SPAG6 in human breast cancer. In silico analysis of the HumanMethylation450 BeadChip and Illumina HiSeq data of The Cancer Genome Atlas (TCGA) was performed in both normal (n=114) and breast cancer patient tissues (n=1104) to determine SPAG6 DNA methylation and expression. Stable SPAG6 overexpressing cancer models for in vitro analysis were obtained by lentivirus-mediated gene delivery in T-47D, MCF-7, MDA-MB-231 and BT-549 breast cancer cells. Subsequently stable mock and SPAG6 cell lines were compared in cellular assays. In addition, involvement of SPAG6 in EMT was analysed by qPCR and immunolabeling experiments. All major molecular subtypes of breast cancer (luminal A, luminal B, basal-type, HER2-enriched) revealed a tumor-specific increased SPAG6 promoter hypermethylation that correlated with strong reduction in SPAG6 mRNA expression. Interestingly, a small group of luminal breast tumors exhibited SPAG6 mRNA overexpression compared to normal breast tissue. SPAG6 overexpression caused a significant reduction (p<0.05) in colony formation in basal MDA-MB-231 and BT-549 cells. In turn, luminal T-47D cells overexpressing SPAG6 showed a significant increase in colony formation (p=0.0004) and both T-47D-and MCF-7 cells overexpressing SPAG6 exhibited a robust increase in migration speed (p<0.0001). In SPAG6-positive T-47D cells SNAIL, TWIST1 and Vimentin expression was found to be significantly upregulated, while E-Cadherin expression was supressed. SPAG6 overexpressing T47D cells showed a typical epithelial-mesenchymal transition (EMT). This was accompanied by a nearly complete displacement of both actin and E-cadherin from cell-cell junctions. Our in vitro analyses give functional evidence that SPAG6 has a profound effect on colony formation, migration and intercellular junction composition in breast cancer cells. Our study is the first to show opposing SPAG6 effects in a single tumour entity depending on the molecular subtype. We propose that SPAG6 might be a key player for inducing the EMT program in luminal-type breast cancers, driving tumour progression and metastasis.

cell biology↗

Inter-Subject Correlation during New Music Listening: A Study of Electrophysiological and Behavioral Responses to Steve Reich's Piano Phase

Musical minimalism utilizes the temporal manipulation of restricted collections of rhythmic, melodic, and/or harmonic materials. One example, Steve Reichs Piano Phase, offers listeners readily audible formal structures containing unpredictable events at local levels. Pattern recurrences may generate strong expectations which are violated by small temporal and pitch deviations. A hyper-detailed listening strategy prompted by these minute deviations stands in contrast to the type of listening engagement typically cultivated around functional tonal Western music. Recent research has suggested that the inter-subject correlation (ISC) of electroencephalographic (EEG) responses to natural audio-visual stimuli objectively indexes a state of "engagement", demonstrating the potential of this approach for analyzing music listening. But can ISCs capture engagement with minimal music, which features less obvious expectation formation and has historically received a wide range of reactions? To approach this question, we collected EEG and continuous behavioral (CB) data while 30 adults listened to an excerpt from Steve Reichs Piano Phase, as well as three controlled manipulations and a popular-music remix of the work. Our analyses reveal that EEG and CB ISC are highest for the remix stimulus and lowest for our most repetitive manipulation. In addition, we found no statistical differences in overall EEG ISC between our most musically meaningful manipulations and Reichs original piece. We also found that aesthetic evaluations corresponded well with overall EEG ISC. Finally we highlight co-occurrences between stimulus events and time-resolved EEG and CB ISC. We offer the CB paradigm as a useful analysis measure and note the value of minimalist compositions as a limit case for studying music listening using EEG ISC. We show that ISC is less effective at measuring engagement with this minimalist stimulus than with popular music genres and argue that this may be due to a difference between the type of engagement measured by ISC and the particular engagement patterns associated with minimalism.

neuroscience↗

Inter-Subject EEG Correlation Reflects Time-Varying Engagement with Natural Music

Musical engagement can be conceptualized through various activities, modes of listening, and listener states--among these a state of focused engagement. Recent research has reported that this state can be indexed by the inter-subject correlation (ISC) of EEG responses to a shared naturalistic stimulus. While statistically significant ISC has been reported during music listening, these reports have considered only correlations computed across entire excerpts and do not provide insights into time-varying engagement. Here we present the first EEG-ISC investigation of time-varying engagement within a musical work. From a sample of 23 adult musicians who listened to a cello concerto movement, we find varying levels of ISC throughout the excerpt. In particular, significant ISC is observed during periods of musical tension that build to climactic highpoints, but not at the highpoints themselves. In addition, we find that a control stimulus retaining envelope characteristics of the intact music, but little other temporal structure, also elicits significant neural correlation, though to a lesser extent than the original excerpt. In all, our findings shed light on temporal dynamics of listener engagement during music listening, establish connections between salient musical events and EEG ISC, and clarify specific listener states that are indexed by this measure.

neuroscience↗

Oscillatory correlates of auditory working memory examined with human electrocorticography

This work examines how sounds are held in auditory working memory (AWM) in humans by examining oscillatory local field potentials (LFPs) in candidate brain regions. Previous fMRI studies by our group demonstrated blood oxygenation level-dependent (BOLD) response increases during maintenance in auditory cortex, inferior frontal cortex and the hippocampus using a paradigm with a delay period greater than 10s. The relationship between such BOLD changes and ensemble activity in different frequency bands is complex, and the long delay period raised the possibility that long-term memory mechanisms were engaged. Here we assessed LFPs in different frequency bands in six subjects with recordings from all candidate brain regions using a paradigm with a short delay period of 3 s. Sustained delay activity was demonstrated in all areas, with different patterns in the different areas. Enhancement in low frequency (delta) power and suppression across higher frequencies (beta/gamma) were demonstrated in primary auditory cortex in medial Heschls gyrus (HG) whilst non-primary cortex showed patterns of enhancement and suppression that altered at different levels of the auditory hierarchy from lateral HG to superior- and middle-temporal gyrus. Inferior frontal cortex showed increasing suppression with increasing frequency. The hippocampus and parahippocampal gyrus showed low frequency increases and high frequency decreases in oscillatory activity. The work demonstrates sustained activity patterns that can only be explained by AWM maintenance, with prominent low-frequency increases in medial temporal lobe regions.

neuroscience↗

Rapid Isothermal Amplification and Portable Detection System for SARS-CoV-2

The COVID-19 pandemic provides an urgent example where a gap exists between availability of state-of-the-art diagnostics and current needs. As assay details and primer sequences become widely known, many laboratories could perform diagnostic tests using methods such as RT-PCR or isothermal RT-LAMP amplification. A key advantage of RT-LAMP based approaches compared to RT-PCR is that RT-LAMP is known to be robust in detecting targets from unprocessed samples. In addition, RT-LAMP assays are performed at a constant temperature enabling speed, simplicity, and point-of-use testing. Here, we provide the details of an RT-LAMP isothermal assay for the detection of SARS-CoV-2 virus with performance comparable to currently approved tests using RT-PCR. We characterize the assay by introducing swabs in virus spiked synthetic nasal fluids, moving the swab to viral transport medium (VTM), and using a volume of that VTM for performing the amplification without an RNA extraction kit. The assay has a Limit-of-Detection (LOD) of 50 RNA copies/L in the VTM solution within 20 minutes, and LOD of 5000 RNA copies/L in the nasal solution. Additionally, we show the utility of this assay for real-time point-of-use testing by demonstrating detection of SARS-CoV-2 virus in less than 40 minutes using an additively manufactured cartridge and a smartphone-based reader. Finally, we explore the speed and cost advantages by comparing the required resources and workflows with RT-PCR. This work could accelerate the development and availability of SARS-CoV-2 diagnostics by proving alternatives to conventional laboratory benchtop tests. Significance StatementAn important limitation of the current assays for the detection of SARS-CoV-2 stem from their reliance on time- and labor-intensive and laboratory-based protocols for viral isolation, lysis, and removal of inhibiting materials. While RT-PCR remains the gold standard for performing clinical diagnostics to amplify the RNA sequences, there is an urgent need for alternative portable platforms that can provide rapid and accurate diagnosis, potentially at the point-of-use. Here, we present the details of an isothermal amplification-based detection of SARS-CoV-2, including the demonstration of a smartphone-based point-of-care device that can be used at the point of sample collection.

bioengineering↗

Trapped Topoisomerase II initiates formation of de novo duplications via the nonhomologous end-joining pathway in yeast

Topoisomerase II (Top2) is an essential enzyme that resolves catenanes between sister chromatids as well as supercoils associated with the over- or under-winding of duplex DNA. Top2 alters DNA topology by making a double-strand break (DSB) in DNA and passing an intact duplex through the break. Each component monomer of the Top2 homodimer nicks one of the DNA strands and forms a covalent phosphotyrosyl bond with the 5 end. Stabilization of this intermediate by chemotherapeutic drugs such as etoposide leads to persistent and potentially toxic DSBs. We describe the isolation of a yeast top2 mutant (top2- F1025Y,R1128G) whose product generates a stabilized cleavage intermediate in vitro. In yeast cells, overexpression of the top2- F1025Y,R1128G allele is associated with a novel mutation signature that is characterized by de novo duplications of DNA sequence that depend on the nonhomologous end-joining pathway of DSB repair. Top2-associated duplications are promoted by the clean removal of the enzyme from DNA ends and are suppressed when the protein is removed as part of an oligonucleotide. TOP2 cells treated with etoposide exhibit the same mutation signature, as do cells that over-express the wild-type protein. These results have implications for genome evolution and are relevant to the clinical use of chemotherapeutic drugs that target Top2. SIGNIFICANCE STATEMENTDNA-strand separation during transcription and replication creates topological problems that are resolved by topoisomerases. These enzymes nick DNA strands to allow strand passage and then reseal the broken DNA to restore its integrity. Topoisomerase II (Top2) nicks complementary DNA strands to create double-strand break (DSBs) intermediates that can be stabilized by chemotherapeutic drugs and are toxic if not repaired. We identified a mutant form of yeast Top2 that forms stabilized cleavage intermediates in the absence of drugs. Over- expression of the mutant Top2 was associated with a unique mutation signature in which small (1-4 bp), unique segments of DNA were duplicated. These de novo duplications required the nonhomologous end-joining pathway of DSB repair, and their Top2-dependence has clinical and evolutionary implications.

molecular biology↗

Anatomic set of mechanical models for the organ of Corti

We build a flexible platform for the study of the mechanical performance of the organ of Corti (OoC) in the transduction of basilar membrane (BM) vibrations to motion of an inner hair cell bundle (IHB). In this platform, each anatomic component of the OoC is described by an equation of motion that can be followed in time. We propose an initial set of models that attempt to capture the nonlinearities of somatic and bundle motility, but can nevertheless be easily handled. The anatomic components that we consider are the outer hair cells (OHCs), the outer hair cell bundles, Deiters cells, Hensen cells, the IHB and various sections of the reticular lamina. We study endolymph fluid motion in the subtectorial gap and then the mutual interactions among the components of the OoC, including the pressure exerted by endolymph. Minute bending of the apical ends of the OHCs can have a significant impact on the passage of motion from the BM to the IHB, including possible critical oscillator behaviour, even without the assistance of tectorial motion, shearing, or bundle motility. Thus, the components of the OoC could cooperate to enhance frequency selectivity, amplitude compression and signal to noise ratio in the passage from the BM to the IHB. Our models also provide a mechanism that could contribute to appropriate amplification of the wave travelling along the cochlea.

systems biology↗

Natural Music Evokes Correlated EEG Responses Reflecting Temporal Structure and Beat

The brain activity of multiple subjects has been shown to synchronize during salient moments of natural stimuli, suggesting that correlation of neural responses indexes a brain state operationally termed engagement. While past electroencephalography (EEG) studies have considered both auditory and visual stimuli, the extent to which these results generalize to music--a temporally structured stimulus for which the brain has evolved specialized circuitry--is less understood. Here we investigated neural correlation during natural music listening by recording dense-array EEG responses from N = 48 adult listeners as they heard real-world musical works, some of which were temporally disrupted through shuffling of short-term segments (measures), reversal, or randomization of phase spectra. We measured neural correlation across responses (inter-subject correlation) and between responses and stimulus envelope fluctuations (stimulus-response correlation) in the time and frequency domains. Stimuli retaining basic musical features evoked significantly correlated neural responses in all analyses. However, while unedited songs were self-reported as most pleasant, time-domain correlations were highest during measure-shuffled versions. Frequency-domain measures of correlation (coherence) peaked at frequencies related to the musical beat, although the magnitudes of these spectral peaks did not explain the observed temporal correlations. Our findings show that natural music evokes significant inter-subject and stimulus-response correlations, and suggest that the neural correlates of musical engagement may be distinct from those of enjoyment.

neuroscience↗

Neural circuitry of a polycystin-mediated hydrodynamic startle response for predator avoidance

Startle responses triggered by aversive stimuli including predators are widespread across animals. These coordinated whole-body actions require the rapid and simultaneous activation of a large number of muscles. Here we study a startle response in a planktonic larva to understand the whole-body circuit implementation of the behavior. Upon encountering water vibrations, larvae of the annelid Platynereis close their locomotor cilia and simultaneously contract the body and raise the parapodia. The startle response is mediated by collar receptor neurons expressing the polycystins PKD1-1 and PKD2-1. CRISPR-generated PKD1-1 and PKD2-1 mutant larvae do not startle and fall prey to a copepod predator at a higher rate. Reconstruction of the whole-body connectome of the collar-receptor-cell circuitry revealed converging feedforward circuits to the ciliary bands and muscles. The wiring diagram suggests circuit mechanisms for the intersegmental and left-right coordination of the response. Our results reveal how polycystin-mediated mechanosensation can trigger a coordinated whole-body effector response involved in predator avoidance.\n\nShort SummaryThe neuronal circuitry of the Platynereis startle response links polycystin-dependent hydrodynamic sensors to muscle and ciliary effector cells

neuroscience↗