Transcript of My Father’s Heroics

This story is an excerpt from a longer interview that was collected as part of the Launching through the Surf: The Dory Fleet of Pacific City project. In this story, Sid Fisher recounts how his father, Walt Fisher, saved him from rolling his dory

Taking turns : bridging the gap between human and animal communication

Funding: a Sofja Kovalevskaja-Award of the Alexander von Humboldt-Foundation awarded to S.P. generously supported the project, as did a Max Planck Institute for Psycholinguistics Levelt Innovation Award awarded to K.H.K. and S.C.V., and a Max Planck Research Group awarded to S.C.V.Language, humans' most distinctive trait, still remains a 'mystery' for evolutionary theory. It is underpinned by a universal infrastructure-cooperative turn-taking-which has been suggested as an ancient mechanism bridging the existing gap between the articulate human species and their inarticulate primate cousins. However, we know remarkably little about turn-taking systems of non-human animals, and methodological confounds have often prevented meaningful cross-species comparisons. Thus, the extent to which cooperative turn-taking is uniquely human or represents a homologous and/or analogous trait is currently unknown. The present paper draws attention to this promising research avenue by providing an overview of the state of the art of turn-taking in four animal taxa-birds, mammals, insects and anurans. It concludes with a new comparative framework to spur more research into this research domain and to test which elements of the human turn-taking system are shared across species and taxa.Publisher PDFPeer reviewe

A novel approach identifies the first transcriptome networks in bats: a new genetic model for vocal communication

Background: Bats are able to employ an astonishingly complex vocal repertoire for navigating their environment and conveying social information. A handful of species also show evidence for vocal learning, an extremely rare ability shared only with humans and few other animals. However, despite their potential for the study of vocal communication, bats remain severely understudied at a molecular level. To address this fundamental gap we performed the first transcriptome profiling and genetic interrogation of molecular networks in the brain of a highly vocal bat species, Phyllostomus discolor. Results: Gene network analysis typically needs large sample sizes for correct clustering, this can be prohibitive where samples are limited, such as in this study. To overcome this, we developed a novel bioinformatics methodology for identifying robust co-expression gene networks using few samples (N=6). Using this approach, we identified tissue-specific functional gene networks from the bat PAG, a brain region fundamental for mammalian vocalisation. The most highly connected network identified represented a cluster of genes involved in glutamatergic synaptic transmission. Glutamatergic receptors play a significant role in vocalisation from the PAG, suggesting that this gene network may be mechanistically important for vocal-motor control in mammals. Conclusion: We have developed an innovative approach to cluster co-expressing gene networks and show that it is highly effective in detecting robust functional gene networks with limited sample sizes. Moreover, this work represents the first gene network analysis performed in a bat brain and establishes bats as a novel, tractable model system for understanding the genetics of vocal mammalian communication

Foxp2 loss of function increases striatal direct pathway inhibition via increased GABA release

JRvR is supported by an RUMC Junior Round grant from the Donders institute Ph.D. program, awarded to NNK and SCV. SCV is supported by a Marie Curie Career Integration Grant (PCIG12-GA-2012-333978) and by a Max Planck Research Group Award. SEF is supported by the Max Planck Society.Heterozygous mutations of the Forkhead-box protein 2 (FOXP2) gene in humans cause childhood apraxia of speech. Loss of Foxp2 in mice is known to affect striatal development and impair motor skills. However, it is unknown if striatal excitatory/inhibitory balance is affected during development and if the imbalance persists into adulthood. We investigated the effect of reduced Foxp2 expression, via a loss-of-function mutation, on striatal medium spiny neurons (MSNs). Our data show that heterozygous loss of Foxp2 decreases excitatory (AMPA receptor-mediated) and increases inhibitory (GABA receptor-mediated) currents in D1 dopamine receptor positive MSNs of juvenile and adult mice. Furthermore, reduced Foxp2 expression increases GAD67 expression, leading to both increased presynaptic content and release of GABA. Finally, pharmacological blockade of inhibitory activity in vivo partially rescues motor skill learning deficits in heterozygous Foxp2 mice. Our results suggest a novel role for Foxp2 in the regulation of striatal direct pathway activity through managing inhibitory drive.Publisher PDFPeer reviewe

The vocal development of the pale spear-nosed bat is dependent on auditory feedback

Funding: The research was funded by the Human Frontiers Science Program (grant no. RGP0058/2016), awarded to L.W. and S.C.V. S.C.V. was supported by a Max Planck Research Group (MPRG) and a UKRI Future Leaders Fellowship (MR/T021985/1). M.S. was funded by a grant from Deutsche Forschungsgemeinschaft (no. wi1518/17).Human vocal development and speech learning require acoustic feedback, and humans who are born deaf do not acquire a normal adult speech capacity. Most other mammals display a largely innate vocal repertoire. Like humans, bats are thought to be one of the few taxa capable of vocal learning as they can acquire new vocalizations by modifying vocalizations according to auditory experiences. We investigated the effect of acoustic deafening on the vocal development of the pale spear-nosed bat. Three juvenile pale spear-nosed bats were deafened, and their vocal development was studied in comparison with an age-matched, hearing control group. The results show that during development the deafened bats increased their vocal activity, and their vocalizations were substantially altered, being much shorter, higher in pitch, and more aperiodic than the vocalizations of the control animals. The pale spear-nosed bat relies on auditory feedback for vocal development and, in the absence of auditory input, species-atypical vocalizations are acquired. This work serves as a basis for further research using the pale spear-nosed bat as a mammalian model for vocal learning, and contributes to comparative studies on hearing impairment across species.Publisher PDFPeer reviewe

The Vocal Repertoire of Pale Spear-Nosed Bats in a Social Roosting Context

Commonly known for their ability to echolocate, bats also use a wide variety of social vocalizations to communicate with one another. However, the full vocal repertoires of relatively few bat species have been studied thus far. The present study examined the vocal repertoire of the pale spear-nosed bat, Phyllostomus discolor, in a social roosting context. Based on visual examination of spectrograms and subsequent quantitative analysis of syllables, eight distinct syllable classes were defined, and their prevalence in different behavioral contexts was examined. Four more syllable classes were observed in low numbers and are described here as well. These results show that P. discolor possesses a rich vocal repertoire, which includes vocalizations comparable to previously reported repertoires of other bat species as well as vocalizations previously undescribed. Our data provide detailed information about the temporal and spectral characteristics of syllables emitted by P. discolor, allowing for a better understanding of the communicative system and related behaviors of this species. Furthermore, this vocal repertoire will serve as a basis for future research using P. discolor as a model organism for vocal communication and vocal learning and it will allow for comparative studies between bat species

Characterisation of CASPR2 deficiency disorder - a syndrome involving autism, epilepsy and language impairment

Background: Heterozygous mutations in CNTNAP2 have been identified in patients with a range of complex phenotypes including intellectual disability, autism and schizophrenia. However heterozygous CNTNAP2 mutations are also found in the normal population. Conversely, homozygous mutations are rare in patient populations and have not been found in any unaffected individuals. Case presentation: We describe a consanguineous family carrying a deletion in CNTNAP2 predicted to abolish function of its protein product, CASPR2. Homozygous family members display epilepsy, facial dysmorphisms, severe intellectual disability and impaired language. We compared these patients with previously reported individuals carrying homozygous mutations in CNTNAP2 and identified a highly recognisable phenotype. Conclusions: We propose that CASPR2 loss produces a syndrome involving early-onset refractory epilepsy, intellectual disability, language impairment and autistic features that can be recognized as CASPR2 deficiency disorder. Further screening for homozygous patients meeting these criteria, together with detailed phenotypic and molecular investigations will be crucial for understanding the contribution of CNTNAP2 to normal and disrupted development

Hyperkinetic stereotyped movements in a boy with biallelic CNTNAP2 variants

SCV was supported by a Max Planck Research Group awarded by the Max Planck Gesellschaft, a Human Frontiers Science Program Grant (RGP0058/2016), and a UKRI Future Leaders Fellowship (MR/T021985/1). MA was supported by an International Max Planck Research School (IMPRS) PhD Fellowship from the Max Planck Institute for Psycholinguistics.Background:  Heterozygous variants in CNTNAP2 have been implicated in a wide range of neurological phenotypes, including intellectual disability (ID), epilepsy, autistic spectrum disorder (ASD), and impaired language. However, heterozygous variants can also be found in unaffected individuals. Biallelic CNTNAP2 variants are rarer and cause a well-defined genetic syndrome known as CASPR2 deficiency disorder, a condition characterised by ID, early-onset refractory epilepsy, language impairment, and autistic features. Case-report : A 7-year-old boy presented with hyperkinetic stereotyped movements that started during early infancy and persisted over childhood. Abnormal movements consisted of rhythmic and repetitive shaking of the four limbs, with evident stereotypic features. Additional clinical features included ID, attention deficit-hyperactivity disorder (ADHD), ASD, and speech impairment, consistent with CASPR2 deficiency disorder. Whole-genome array comparative genomic hybridization detected a maternally inherited 0.402 Mb duplication, which involved intron 1, exon 2, and intron 2 of CNTNAP2 (c.97 +?_209-?dup). The affected region in intron 1 contains a binding site for the transcription factor FOXP2, potentially leading to abnormal CNTNAP2 expression regulation. Sanger sequencing of the coding region of CNTNAP2 also identified a paternally-inherited missense variant c.2752C > T, p.(Leu918Phe). Conclusion : This case expands the molecular and phenotypic spectrum of CASPR2 deficiency disorder, suggesting that Hyperkinetic stereotyped movements may be a rare, yet significant, clinical feature of this complex neurological disorder. Furthermore, the identification of an in-frame, largely non-coding duplication in CNTNAP2 points to a sophisticated underlying molecular mechanism, likely involving impaired FOXP2 binding.Publisher PDFPeer reviewe

Neuroanatomy of the grey seal brain : bringing pinnipeds into the neurobiological study of vocal learning

N.H. is supported by funding from an International Max Planck Research School (IMPRS) for language sciences fellowship grant, and the work of N.H. and S.C.V. was supported by a Max Planck Research Group (MPRG) awarded to S.C.V. The work of L.V. and A.R. was supported by a Max Planck Research Group (MPRG) awarded to A.R. S.C.V. was also supported by a Human Frontiers Science Program (HFSP) Research grant (grant no. RGP0058/2016) and a UKRI Future Leaders Fellowship (grant no. MR/T021985/1).Comparative animal studies of complex behavioural traits, and their neurobiological underpinnings, can increase our understanding of their evolution, including in humans. Vocal learning, a potential precursor to human speech, is one such trait. Mammalian vocal learning is under-studied: most research has either focused on vocal learning in songbirds or its absence in non-human primates. Here, we focus on a highly promising model species for the neurobiology of vocal learning: grey seals (Halichoerus grypus). We provide a neuroanatomical atlas (based on dissected brain slices and magnetic resonance images), a labelled MRI template, a three-dimensional model with volumetric measurements of brain regions, and histological cortical stainings. Four main features of the grey seal brain stand out: (i) it is relatively big and highly convoluted; (ii) it hosts a relatively large temporal lobe and cerebellum; (iii) the cortex is similar to that of humans in thickness and shows the expected six-layered mammalian structure; (iv) there is expression of FoxP2 present in deeper layers of the cortex; FoxP2 is a gene involved in motor learning, vocal learning, and spoken language. Our results could facilitate future studies targeting the neural and genetic underpinnings of mammalian vocal learning, thus bridging the research gap from songbirds to humans and non-human primates. Our findings are relevant not only to vocal learning research but also to the study of mammalian neurobiology and cognition more in general.PostprintPeer reviewe

Contradictory phylogenetic signals in the laurasiatheria anomaly zone

G.M.H. was funded by a UCD Ad Astra Fellowship. C.L. was funded by a UCD Ad Astra studentship. L.R. was funded by an SFI Centre for Research Training in Genomics Data Science grant (18/CRT/6214). L.M.D. was supported in part by NSF awards 1838273 and 2032063. E.C.T. and T.L. were funded by an SFI Frontiers for the Future Programme grant (19/FFP/6790).Relationships among laurasiatherian clades represent one of the most highly disputed topics in mammalian phylogeny. In this study, we attempt to disentangle laurasiatherian interordinal relationships using two independent genome-level approaches: (1) quantifying retrotransposon presence/absence patterns, and (2) comparisons of exon datasets at the levels of nucleotides and amino acids. The two approaches revealed contradictory phylogenetic signals, possibly due to a high level of ancestral incomplete lineage sorting. The positions of Eulipotyphla and Chiroptera as the first and second earliest divergences were consistent across the approaches. However, the phylogenetic relationships of Perissodactyla, Cetartiodactyla, and Ferae, were contradictory. While retrotransposon insertion analyses suggest a clade with Cetartiodactyla and Ferae, the exon dataset favoured Cetartiodactyla and Perissodactyla. Future analyses of hitherto unsampled laurasiatherian lineages and synergistic analyses of retrotransposon insertions, exon and conserved intron/intergenic sequences might unravel the conflicting patterns of relationships in this major mammalian clade.Publisher PDFPeer reviewe