An interdisciplinary approach to investigate collective cell migration in neural crest

The neural crest serves as a powerful and tractable model paradigm for understanding collective cell migration. The neural crest cell populations are well-known for their long-distance collective migration and contribution to diverse cell lineages during vertebrate development. If neural crest cells fail to reach a target or populate an incorrect location, then improper cell differentiation or uncontrolled cell proliferation can result. A wide range of interdisciplinary studies has been carried out to understand the response of neural crest cells to different stimuli and their ability to migrate to distant targets. In this critical commentary, we illustrate how an interdisciplinary collaboration involving experimental and mathematical modeling has led to a deeper understanding of cranial neural crest cell migration. We identify open questions and propose possible ways to start answering some of the challenges arising.     

Insomnia does not affect heart rate changes when young adults watch humorous films: An exploratory study

Emotional reactivity in insomnia is affected both subjectively and on a physiological level for negative emotional material, but little is known about reactions to positive stimuli. We here investigated whether in younger adult insomnia patients, presentation of short humorous films would lead to heart rate decreases during and after film viewing, as compared to heart rate changes when falling asleep. Investigating 20 participants with DSM‐5‐diagnosed insomnia and 18 participants without insomnia, we found that heart rate decreased when falling asleep, increased when watching humorous films and returned to normal values afterwards for all participants. Film‐related heart rate increases were strongly related to humour ratings of the films. No differences were found between those with and without insomnia on subjective ratings of the films, film‐related heart rate changes or when falling asleep. We conclude that the experience of positive daily life stimuli in younger adults is not affected by insomnia in our study, despite insomnia having a known more profound effect on negative stimuli. Future studies exploring insomnia‐related autonomous nervous system responses combining different neurophysiological modalities should confirm our findings.     

Mutant C9orf72 human iPSC-derived astrocytes cause non-cell autonomous motor neuron pathophysiology

Mutations in C9orf72 are the most common genetic cause of amyotrophic lateral sclerosis (ALS). Accumulating evidence implicates astrocytes as important non-cell autonomous contributors to ALS pathogenesis, although the potential deleterious effects of astrocytes on the function of motor neurons remains to be determined in a completely humanized model of C9orf72-mediated ALS. Here, we use a human iPSC-based model to study the cell autonomous and non-autonomous consequences of mutant C9orf72 expression by astrocytes. We show that mutant astrocytes both recapitulate key aspects of C9orf72-related ALS pathology and, upon co-culture, cause motor neurons to undergo a progressive loss of action potential output due to decreases in the magnitude of voltage-activated Na⁺ and K⁺ currents. Importantly, CRISPR/Cas-9 mediated excision of the C9orf72 repeat expansion reverses these phenotypes, confirming that the C9orf72 mutation is responsible for both cell-autonomous astrocyte pathology and non-cell autonomous motor neuron pathophysiology.     

Paracingulate Sulcus Length Is Shorter in Voice-Hearers Regardless of Need for Care

Hallucinations—while often considered an indication of mental illness—are commonly experienced by those without a need for clinical care. These nonclinical voice-hearers offer an opportunity to investigate hallucinations in the absence of confounds inherent to the clinical state. Recent work demonstrates an association between auditory verbal hallucinations (AVH) and structural variability in paracingulate sulcus (PCS) of medial prefrontal cortex in a clinical population. However, before PCS length may be considered a biomarker for clinical hallucination risk, it is necessary to investigate PCS structure in a nonclinical population of voice-hearers with AVH phenomenology similar to those of their clinical counterparts. In the current study, PCS length was measured from T1-weighted structural MRI scans of four groups of participants: (1) voice-hearers with a psychotic disorder (n = 15); (2) voice-hearers without a psychotic disorder (n = 15); (3) nonvoice-hearers with a psychotic disorder (n = 14); and (4) nonvoice-hearers without a psychotic disorder (n = 15). There was a main effect of AVH status—but not psychosis—on right PCS length, with no interaction of AVH and psychosis. Participants with AVH exhibited reduced right PCS length compared to participants without AVH (mean reduction = 8.8 mm, P < 0.05). While past studies have demonstrated decreased PCS length in clinical voice-hearers, ours is the first demonstration that shorter right PCS extends to nonclinical voice-hearers. Our findings support the hypothesis that differences in PCS length are related to the propensity to hear voices and not to illness, consistent with a continuum model of voice-hearing.