Sustained synchronized neuronal network activity in a human astrocyte co-culture system

Impaired neuronal network function is a hallmark of neurodevelopmental and neurodegenerative disorders such as autism, schizophrenia, and Alzheimer's disease and is typically studied using genetically modified cellular and animal models. Weak predictive capacity and poor translational value of these models urge for better human derived in vitro models. The implementation of human induced pluripotent stem cells (hiPSCs) allows studying pathologies in differentiated disease-relevant and patient-derived neuronal cells. However, the differentiation process and growth conditions of hiPSC-derived neurons are non-trivial. In order to study neuronal network formation and (mal) function in a fully humanized system, we have established an in vitro co-culture model of hiPSC-derived cortical neurons and human primary astrocytes that recapitulates neuronal network synchronization and connectivity within three to four weeks after final plating. Live cell calcium imaging, electrophysiology and high content image analyses revealed an increased maturation of network functionality and synchronicity over time for co-cultures compared to neuronal monocultures. The cells express GABAergic and glutamatergic markers and respond to inhibitors of both neurotransmitter pathways in a functional assay. The combination of this co-culture model with quantitative imaging of network morphofunction is amenable to high throughput screening for lead discovery and drug optimization for neurological diseases

Glycine and Glycine Receptor Signalling in Non-Neuronal Cells

Glycine is an inhibitory neurotransmitter acting mainly in the caudal part of the central nervous system. Besides this neurotransmitter function, glycine has cytoprotective and modulatory effects in different non-neuronal cell types. Modulatory effects were mainly described in immune cells, endothelial cells and macroglial cells, where glycine modulates proliferation, differentiation, migration and cytokine production. Activation of glycine receptors (GlyRs) causes membrane potential changes that in turn modulate calcium flux and downstream effects in these cells. Cytoprotective effects were mainly described in renal cells, hepatocytes and endothelial cells, where glycine protects cells from ischemic cell death. In these cell types, glycine has been suggested to stabilize porous defects that develop in the plasma membranes of ischemic cells, leading to leakage of macromolecules and subsequent cell death. Although there is some evidence linking these effects to the activation of GlyRs, they seem to operate in an entirely different mode from classical neuronal subtypes

Multimodal stance-taking in interaction—A systematic literature review

Stance-taking, the public act of positioning oneself toward objects, people or states of affairs, has been studied in many fields of research. Recently, its multimodal realization in interaction has received increasing attention. The current contribution aims to take stock of research on multimodal stance-taking so far, and to present possible avenues for future research. We systematically gathered and appraised 76 articles that investigate the involvement of bodily-visual resources in stance-taking in interaction. The critical appraisal focused on two dimensions of the stance act: form-function relations constituting it, and its dynamic organization in interaction. Regarding form-function relations, we found systematic involvement of specific bodily-visual resources in different stance acts, as well as patterns of multimodal intensification and mitigation of stances. As for its dynamic organization, the review discusses how stance-taking is organized temporally throughout an interaction, with all participants involved carefully negotiating and adapting their stances to one another. Finally, attention is paid to the broader context of stance-taking, including its role in different social and societal contexts. Based on this review, we were able to identify several gaps in the literature, and avenues for future research. We argue that much potential for broadening the scope of research lies in increasing the methodological diversity in approaching multimodal stance-taking, as well as in cross-linguistic studies and varying settings and participant constellations. In conclusion, research into multimodal stance-taking is vibrant, with ample opportunities for future work. This review can be considered as a call to action to move beyond the premise that stance-taking is multimodal, and further investigate this intriguing and fundamental human capacity

Alpha2-Containing Glycine Receptors Promote Neonatal Spontaneous Activity of Striatal Medium Spiny Neurons and Support Maturation of Glutamatergic Inputs

Glycine receptors (GlyRs) containing the α2 subunit are highly expressed in the developing brain, where they regulate neuronal migration and maturation, promote spontaneous network activity and subsequent development of synaptic connections. Mutations in GLRA2 are associated with autism spectrum disorder, but the underlying pathophysiology is not described yet. Here, using Glra2-knockout mice, we found a GlyR-dependent effect on neonatal spontaneous activity of dorsal striatum medium spiny neurons (MSNs) and maturation of the incoming glutamatergic innervation. Our data demonstrate that functional GlyRs are highly expressed in MSNs of one-week-old mice, but they do not generate endogenous chloride-mediated tonic or phasic current. Despite of that, knocking out the Glra2 severely affects the shape of action potentials and impairs spontaneous activity and the frequency of miniature AMPA receptor-mediated currents in MSNs. This reduction in spontaneous activity and glutamatergic signaling can attribute to the observed changes in neonatal behavioral phenotypes as seen in ultrasonic vocalizations and righting reflex. In adult Glra2-knockout animals, the glutamatergic synapses in MSNs remain functionally underdeveloped. The number of glutamatergic synapses and release probability at presynaptic site remain unaffected, but the amount of postsynaptic AMPA receptors is decreased. This deficit is a consequence of impaired development of the neuronal circuitry since acute inhibition of GlyRs by strychnine in adult MSNs does not affect the properties of glutamatergic synapses. Altogether, these results demonstrate that GlyR-mediated signaling supports neonatal spontaneous MSN activity and, in consequence, promotes the functional maturation of glutamatergic synapses on MSNs. The described mechanism might shed light on the pathophysiological mechanisms in GLRA2-linked autism spectrum disorder cases

Context shapes interactive alignment: the role of cumulative priming

A growing body of evidence shows that dialogue involves a process of synchronisation across speakers at different semiotic levels. In this paper, we study which factors predict this synchronisation process at the lexical and gestural level. A multifactorial analysis based on a video corpus of dyadic interactions reveals that cumulative priming is the key factor at both levels. More than temporal or social factors, the number of preceding lexical or gestural references predicts which word or gesture participants will use. However, there is a crucial difference between the two modalities. At the lexical level cumulative priming by the interlocutor is crucial, whereas for gesture participants appear to draw on their own previous representations. A comparison with related studies shows that high-level, referential synchronisation and low-level, behavioural synchronisation seem to be governed by different rules. Models of human interaction that focus on synchronisation, should take both strands of research into account.status: publishe

InSight Interaction: a multimodal and multifocal dialogue corpus

© 2014, Springer Science+Business Media Dordrecht. Research on the multimodal aspects of interactional language use requires high-quality multimodal resources. In contrast to the vast amount of available written language corpora and collections of transcribed spoken language, truly multimodal corpora including visual as well as auditory data are scarce. In this paper, we first discuss a few notable exceptions that do provide high-quality and multiple-angle video recordings of face-to-face conversations. We then present a new multimodal corpus design that adds two dimensions to the existing resources. First, the recording set-up was designed in such a way as to have a full view of the dialogue partners’ gestural behaviour, including hand gestures, facial expressions and body posture. Second, by recording the participant perspective and behaviour during conversation, using head-mounted scene cameras and eye-trackers, we obtained a 3D landscape of the conversation, with detailed production information (scene camera and sound) and indices of cognitive processing (eye movements for gaze analysis) for both participants. In its current form, the resulting InSight Interaction Corpus consists of 15 recorded face-to-face interactions of 20 min each, of which five have been transcribed and annotated for a range of linguistic and gestural features, using the ELAN multimodal annotation tool.status: publishe

What you see is what you do: on the relationship between gaze and gesture in multimodal alignment

Interactive language use inherently involves a process of coordination, which often leads to matching behaviour between interlocutors at different semiotic channels. We study this process of interactive alignment from a multimodal perspective: using data from head-mounted eye-trackers in a corpus of face-to-face conversations, we measure which effect gaze fixations by speakers (on their own gestures, condition 1) and fixations by interlocutors (on the gestures by those speakers, condition 2) have on subsequent gesture production by those interlocutors. The results show there is a significant effect of interlocutor gaze (condition 2), but not of speaker gaze (condition 1) on the amount of gestural alignment, with an interaction between the conditions.license: Copyright © UK Cognitive Linguistics Association 2015 status: publishe

Explaining interactive alignment: A multimodal and multifactorial account

© 2016 A growing body of evidence shows that dialogue involves a process of synchronization across speakers at different semiotic levels. In this paper, we study which factors predict this synchronization process at the lexical and gestural level. A multifactorial analysis based on a video corpus of dyadic interactions reveals that cumulative priming can account for alignment at both levels. However, there is a crucial difference between the two modalities: at the lexical level cumulative priming is the only factor with explanatory power, whereas at the gestural level, alignment is best explained by how talkative speakers are, by whether or not two gestures overlap, and whether the gestures occur towards the end of the conversations. A comparison with related studies shows that high-level, referential synchronization and low-level, behavioural synchronization seem to be governed by different rules. Models of human interaction that focus on synchronization, should take both strands of research into account.publisher: Elsevier articletitle: Explaining interactive alignment: A multimodal and multifactorial account journaltitle: Journal of Pragmatics articlelink: http://dx.doi.org/10.1016/j.pragma.2016.07.002 content_type: article copyright: © 2016 Published by Elsevier B.V.status: publishe

Bidirectionality in multimodal interaction

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