Engineering an in vitro retinothalamic nerve model.

Understanding the retinogeniculate pathway in vitro can offer insights into its development and potential for future therapeutic applications. This study presents a Polydimethylsiloxane-based two-chamber system with axon guidance channels, designed to replicate unidirectional retinogeniculate signal transmission in vitro. Using embryonic rat retinas, we developed a model where retinal spheroids innervate thalamic targets through up to 6 mm long microfluidic channels. Using a combination of electrical stimulation and functional calcium imaging we assessed how channel length and electrical stimulation frequency affects thalamic target response. In the presented model we integrated up to 20 identical functional retinothalamic neural networks aligned on a single transparent microelectrode array, enhancing the robustness and quality of recorded functional data. We found that network integrity depends on channel length, with 0.5-2 mm channels maintaining over 90% morphological and 50% functional integrity. A reduced network integrity was recorded in longer channels. The results indicate a notable reduction in forward spike propagation in channels longer than 4 mm. Additionally, spike conduction fidelity decreased with increasing channel length. Yet, stimulation-induced thalamic target activity remained unaffected by channel length. Finally, the study found that a sustained thalamic calcium response could be elicited with stimulation frequencies up to 31 Hz, with higher frequencies leading to transient responses. In conclusion, this study presents a high-throughput platform that demonstrates how channel length affects retina to brain network formation and signal transmission in vitro.

Effects of a soft robotic exosuit on the quality and speed of overground walking depends on walking ability after stroke.

BACKGROUND: Soft robotic exosuits can provide partial dorsiflexor and plantarflexor support in parallel with paretic muscles to improve poststroke walking capacity. Previous results indicate that baseline walking ability may impact a user's ability to leverage the exosuit assistance, while the effects on continuous walking, walking stability, and muscle slacking have not been evaluated. Here we evaluated the effects of a portable ankle exosuit during continuous comfortable overground walking in 19 individuals with chronic hemiparesis. We also compared two speed-based subgroups (threshold: 0.93 m/s) to address poststroke heterogeneity. METHODS: We refined a previously developed portable lightweight soft exosuit to support continuous overground walking. We compared five minutes of continuous walking in a laboratory with the exosuit to walking without the exosuit in terms of ground clearance, foot landing and propulsion, as well as the energy cost of transport, walking stability and plantarflexor muscle slacking. RESULTS: Exosuit assistance was associated with improvements in the targeted gait impairments: 22% increase in ground clearance during swing, 5° increase in foot-to-floor angle at initial contact, and 22% increase in the center-of-mass propulsion during push-off. The improvements in propulsion and foot landing contributed to a 6.7% (0.04 m/s) increase in walking speed (R2 = 0.82). This enhancement in gait function was achieved without deterioration in muscle effort, stability or cost of transport. Subgroup analyses revealed that all individuals profited from ground clearance support, but slower individuals leveraged plantarflexor assistance to improve propulsion by 35% to walk 13% faster, while faster individuals did not change either. CONCLUSIONS: The immediate restorative benefits of the exosuit presented here underline its promise for rehabilitative gait training in poststroke individuals.

Topologically controlled circuits of human iPSC-derived neurons for electrophysiology recordings.

Bottom-up neuroscience, which consists of building and studying controlled networks of neurons in vitro, is a promising method to investigate information processing at the neuronal level. However, in vitro studies tend to use cells of animal origin rather than human neurons, leading to conclusions that might not be generalizable to humans and limiting the possibilities for relevant studies on neurological disorders. Here we present a method to build arrays of topologically controlled circuits of human induced pluripotent stem cell (iPSC)-derived neurons. The circuits consist of 4 to 50 neurons with well-defined connections, confined by microfabricated polydimethylsiloxane (PDMS) membranes. Such circuits were characterized using optical imaging and microelectrode arrays (MEAs), suggesting the formation of functional connections between the neurons of a circuit. Electrophysiology recordings were performed on circuits of human iPSC-derived neurons for at least 4.5 months. We believe that the capacity to build small and controlled circuits of human iPSC-derived neurons holds great promise to better understand the fundamental principles of information processing and storing in the brain.