Publications

Helping behavior in rodents provides a powerful model for studying neurobiological underpinnings of prosocial motivation. Previously, rats allowed to release a trapped conspecific demonstrated prosocial motivation selectively toward ingroup members. Here, a refined version of the helping behavior test (HBT) allowed trapped rats to be freed without ensuing social contact, dissociating social from prosocial reward. In this "separated" HBT (SHBT), helping was not biased, as rats equally released ingroup and outgroup members. Whole brain c-Fos mapping revealed a subset of the standard HBT prosocial brain network engaged in the SHBT. Observed absence of activity in the nucleus accumbens (NAc) instigated a chemogenetic investigation of this region. NAc activity was not necessary for helping, but significantly reduced affiliative behavior. The recruitment of Oxtr+ cells in sensory cortices suggests modulated sensory processing. Together, these findings dissociate neural circuits underlying social and prosocial motivation and provide a mechanistic framework for studying mammalian prosocial behavior.

JTD Keywords: Basolateral amygdala, Brain, Cingulate, Cognition, Empathy, Involvement, Maternal-behavior, Nucleus-accumbens core, Orbitofrontal cortex, Oxytocin

Several procedures have been developed to enhance the rehabilitation of stroke patients. However, most techniques struggle to promote sustained recovery in the months following the treatment. Therefore, it is essential to understand the mechanisms that can be harnessed during treatment to potentiate retention of benefits and sustained recovery. While stroke patients often suffer from thalamocortical dysrhythmia (TCD), a perturbation in alpha (8-13 Hz) rhythms caused by decreased excitation in the cortico-thalamic projections, the functional relevance of TCD in stroke patients is not yet clear. We propose that TCD can be counteracted by combining focal stimulation of the motor cortex with virtual-reality (VR) based rehabilitation, which engages distributed networks associated with goal-oriented behavior. Critically, we investigate whether this can be the key to promoting sustained recovery in stroke patients. We compare thalamocortical rhythms and behavioral recovery in patients receiving Sham and bilateral tDCS stimulation of the motor cortex during therapy with the Rehabilitation Gaming System (RGS). Our results reveal that patients in the tDCS group show a sustained recovery in all clinical scales up to three months post-treatment, as opposed to the Sham group. Furthermore, we demonstrate that the slowing down of alpha rhythms can be counteracted by transcranial direct-current stimulation (tDCS), with a particular role for enhancing the excitability of parietal areas. That said, we found no correlation between changes in alpha rhythms and motor recovery. On one hand, our findings suggest that sustained recovery can be potentiated by tDCS-enhanced VR-based rehabilitation. On the other hand, enhancing the excitability of parietal areas while recruiting brain networks associated with goal-oriented behavior can successfully counteract TCD, even though this is likely not the main driver of sustained motor recovery.

JTD Keywords: Activation, Alpha rhythms, Deep brain-stimulation, Direct-current stimulation, Excitatory-inhibitory balance, Guidelines, Human thalamus, Involvement, Motor recovery, Quality-of-life, Rehabilitation, Sensitivity, Stroke, Transcranial direct-current stimulation

Mesenchymal condensation is a prevalent morphogenetic transition that is essential in chondrogenesis. However, the current understanding of condensation mechanisms is limited. In vivo, progenitor cells directionally migrate from the surrounding loose mesenchyme towards regions of increasing matrix adherence (the condensation centers), which is accompanied by the upregulation of fibronectin. Here, we focused on the mechanisms of cell migration during mesenchymal cell condensation and the effects of matrix adherence. Dendrimer-based nanopatterns of the cell-adhesive peptide arginine-glycine-aspartic acid (RGD), which is present in fibronectin, were used to regulate substrate adhesion. We recorded collective and single-cell migration of mesenchymal stem cells, under chondrogenic induction, using live-cell imaging. Our results show that the cell migration mode of single cells depends on substrate adhesiveness, and that cell directionality controls cell condensation and the fusion of condensates. Inhibition experiments revealed that cell???cell interactions mediated by N-cadherin (also known as CDH2) are also pivotal for directional migration of cell condensates by maintaining cell???cell cohesion, thus suggesting a fine interplay between cell???matrix and cell???cell adhesions. Our results shed light on the role of cell interactions with a fibronectin-depositing matrix during chondrogenesis in vitro, with possible applications in regenerative medicine.

JTD Keywords: Alpha-v-beta-3, Arginine-glycine-aspartic acid, Cell migration, Chondrogenesis, Dynamics, Expression, Fibronectin, Gastrulation, Involvement, Mechanisms, Mesenchymal condensation, Model, N-cadherin, Nanopatterned substrates, Rgd

JTD Keywords: Adhesion, Aggregation factor, Cell-binding, Glycan, Involvement, Site, Sponge, Surface guided reassociation