Royal Academy of Art

Although there is a growing interest in the more-than-human, human-centred approaches are still dominant in HCI and design research. Emerging more-than-human approaches aim at decentring the human perspective in the design process while connecting human and non-human actors. This workshop explores strategies to bridge more-than-human with human-centred design and emphasises that decentring is not equal to disconnecting the human designer from being a human. Instead, we intend to elaborate on how our being in the world –co-shaped by non-human entities– can be experienced through decentring our individual human perspectives and re-connecting us to other perspectives, be they human or non-human. We start tackling the following questions: How do designers position themselves in more-than-human approaches? How does decentring the human perspective lead to growing empathy and care? What is a designer’s responsibility within more-than-human approaches?

The role of facial feedback in facial emotion recognition remains controversial, partly due to limitations of the existing methods to manipulate the activation of facial muscles, such as voluntary posing of facial expressions or holding a pen in the mouth. These procedures are indeed limited in their control over which muscles are (de)activated when and to what degree. To overcome these limitations and investigate in a more controlled way if facial emotion recognition is modulated by one’s facial muscle activity, we used computer-controlled facial neuromuscular electrical stimulation (fNMES). In a pre-registered EEG experiment, ambiguous facial expressions were categorised as happy or sad by 47 participants. In half of the trials, weak smiling was induced through fNMES delivered to the bilateral Zygomaticus Major muscle for 500 ms. The likelihood of categorising ambiguous facial expressions as happy was significantly increased with fNMES, as shown with frequentist and Bayesian linear mixed models. Further, fNMES resulted in a reduction of P1, N170 and LPP amplitudes. These findings suggest that fNMES-induced facial feedback can bias facial emotion recognition and modulate the neural correlates of face processing. We conclude that fNMES has potential as a tool for studying the effects of facial feedback.

Gene therapy is a powerful approach to promote spinal cord regeneration. For a clinical application it is important to restrict therapeutic gene expression to the appropriate time window to limit unwanted side effects. The doxycycline (dox)-inducible system is a widely used regulatable gene expression platform, however, this system depends on a bacterial-derived immunogenic transactivator. The foreign origin of this transactivator prevents reliable regulation of therapeutic gene expression and currently limits clinical translation. The glycine-alanine repeat (GAR) of Epstein-Barr virus nuclear antigen-1 protein inhibits its presentation to cytotoxic T cells, allowing virus-infected cells to evade the host immune system. We developed a chimeric transactivator (GARrtTA) and show that GARrtTA has an immune-evading advantage over “classical” rtTA in vivo. Direct comparison of lentiviral vectors expressing rtTA and GARrtTA in the rat spinal cord shows that the GARrtTA system is inducible for 6 doxycycline-cycles over a 47 week period, whereas with the rtTA-based system luciferase reporter expression declines during the 3rd cycle and is no longer re-inducible, indicating that GARrtTA provides an immune-advantage over rtTA. Immunohistochemistry revealed that GARrtTA expressing cells in the spinal cord appear healthier and survive better than rtTA expressing cells. Characterization of the immune response shows that expression of GARrtTA, in contrast to rtTA, does not recruit cytotoxic T-cells to the transduced spinal cord. This study demonstrates that fusion of the GAR domain to rtTA results in a functional doxycycline-inducible transactivator with a clear immune-advantage over the classical rtTA in vivo.

Abstract Parvalbumin-expressing (PV+) basket cells are fast-spiking interneurons that exert critical control over local neuronal circuit activity and oscillations. PV+interneuron axons are partially myelinated but the electrical and metabolic roles of myelin in axonal functions remain poorly understood. Here, we developed Cre-dependent AAV vectors for cell type-specific investigation of mitochondria with genetically encoded fluorescent probes. Single-cell reconstructions and mining of ultrastructural data revealed that mitochondria selectively cluster to myelinated segments of PV+basket cell axons. Cuprizone-induced demyelination abolished mitochondrial clustering in PV+axons but increased axonal mitochondrial densities in excitatory axons. The internodal clustering of mitochondria was preserved with genetic deletion of myelin basic protein, suggesting that noncompacted myelin is sufficient. Finally, two-photon imaging of action potential-evoked mitochondrial calcium (mt-Ca2+) responses showed that internodal mitochondria did not contribute in buffering activity-dependent Ca2+influx. These findings suggest that oligodendrocyte-PV+axon signaling assembles mitochondria to branch selectively fine-tune metabolic demands.

Semaphorins, originally discovered as guidance cues for developing axons, are involved in many processes that shape the nervous system during development, from neuronal proliferation and migration to neuritogenesis and synapse formation. Interestingly, the expression of many Semaphorins persists after development. For instance, Semaphorin 3A is a component of perineuronal nets, the extracellular matrix structures enwrapping certain types of neurons in the adult CNS, which contribute to the closure of the critical period for plasticity. Semaphorin 3G and 4C play a crucial role in the control of adult hippocampal connectivity and memory processes, and Semaphorin 5A and 7A regulate adult neurogenesis. This evidence points to a role of Semaphorins in the regulation of adult neuronal plasticity. In this review, we address the distribution of Semaphorins in the adult nervous system and we discuss their function in physiological and pathological processes.

SummaryThe cerebellum is involved in the control of voluntary and autonomic rhythmic behaviors, yet it is unclear to what extent it coordinates these in concert. We studied Purkinje cell activity during unperturbed and perturbed respiration in lobules simplex, crus 1, and crus 2. During unperturbed (eupneic) respiration, complex spike and simple spike activity encode the phase of ongoing sensorimotor processing. In contrast, when the respiratory cycle is perturbed by whisker stimulation, mice concomitantly protract their whiskers and advance their inspiration in a phase-dependent manner, preceded by increased simple spike activity. This phase advancement of respiration in response to whisker stimulation can be mimicked by optogenetic stimulation of Purkinje cells and prevented by cell-specific genetic modification of their AMPA receptors, hampering increased simple spike firing. Thus, the impact of Purkinje cell activity on respiratory control is context and phase dependent, highlighting a coordinating role for the cerebellar hemispheres in aligning autonomic and sensorimotor behaviors.

Ventral root avulsion leads to severe motoneuron degeneration and prolonged distal nerve denervation. After a critical period, a state of chronic denervation develops as repair Schwann cells lose their pro-regenerative properties and inhibitory factors such as CSPGs accumulate in the denervated nerve. In rats with ventral root avulsion injuries, we combined timed GDNF gene therapy delivered to the proximal nerve roots with the digestion of inhibitory CSPGs in the distal denervated nerve using sustained lentiviral-mediated chondroitinase ABC (ChABC) enzyme expression. Following reimplantation of lumbar ventral roots, timed GDNF-gene therapy enhanced motoneuron survival up to 45weeks and improved axonal outgrowth, electrophysiological recovery, and muscle reinnervation. Despite a timed GDNF expression period, a subset of animals displayed axonal coils. Lentiviral delivery of ChABC enabled digestion of inhibitory CSPGs for up to 45weeks in the chronically denervated nerve. ChABC gene therapy alone did not enhance motoneuron survival, but led to improved muscle reinnervation and modest electrophysiological recovery during later stages of the regeneration process. Combining GDNF treatment with digestion of inhibitory CSPGs did not have a significant synergistic effect. This study suggests a delicate balance exists between treatment duration and concentration in order to achieve therapeutic effects.