Synaptogenic gene therapy with FGF22 improves circuit plasticity and functional recovery following spinal cord injury.

Functional recovery following incomplete spinal cord injury (SCI) depends on the rewiring of motor circuits during which supraspinal connections form new contacts onto spinal relay neurons. We have recently identified a critical role of the presynaptic organizer FGF22 for the formation of new synapses in the remodeling spinal cord. Here, we now explore whether and how targeted overexpression of FGF22 can be used to mitigate the severe functional consequences of SCI.

Coordinated neurostimulation promotes circuit rewiring and unlocks recovery after spinal cord injury.

Functional recovery after incomplete spinal cord injury depends on the effective rewiring of neuronal circuits. Here, we show that selective chemogenetic activation of either corticospinal projection neurons or intraspinal relay neurons alone led to anatomically restricted plasticity and little functional recovery. In contrast, coordinated stimulation of both supraspinal centers and spinal relay stations resulted in marked and circuit-specific enhancement of neuronal rewiring, shortened EMG latencies, and improved locomotor recovery.

Nano-positioning and tubulin conformation contribute to axonal transport regulation of mitochondria along microtubules.

Correct spatiotemporal distribution of organelles and vesicles is crucial for healthy cell functioning and is regulated by intracellular transport mechanisms. Controlled transport of bulky mitochondria is especially important in polarized cells such as neurons that rely on these organelles to locally produce energy and buffer calcium. Mitochondrial transport requires and depends on microtubules that fill much of the available axonal space.

Selective plasticity of callosal neurons in the adult contralesional cortex following murine traumatic brain injury.

Traumatic brain injury (TBI) results in deficits that are often followed by recovery. The contralesional cortex can contribute to this process but how distinct contralesional neurons and circuits respond to injury remains to be determined. To unravel adaptations in the contralesional cortex, we used chronic in vivo two-photon imaging.

Label-Free Imaging of Membrane Potentials by Intramembrane Field Modulation, Assessed by Second Harmonic Generation Microscopy.

Optical interrogation of cellular electrical activity has proven itself essential for understanding cellular function and communication in complex networks. Voltage-sensitive dyes are important tools for assessing excitability but these highly lipophilic sensors may affect cellular function. Label-free techniques offer a major advantage as they eliminate the need for these external probes.

A deep learning-based toolbox for Automated Limb Motion Analysis (ALMA) in murine models of neurological disorders.

In neuroscience research, the refined analysis of rodent locomotion is complex and cumbersome, and access to the technique is limited because of the necessity for expensive equipment. In this study, we implemented a new deep learning-based open-source toolbox for Automated Limb Motion Analysis (ALMA) that requires only basic behavioral equipment and an inexpensive camera. The ALMA toolbox enables the consistent and comprehensive analyses of locomotor kinematics and paw placement and can be applied to neurological conditions affecting the brain and spinal cord.

Chemogenetic approaches to unravel circuit wiring and related behavior after spinal cord injury.

A critical shortcoming of the central nervous system is its limited ability to repair injured nerve connections. Trying to overcome this limitation is not only relevant to understand basic neurobiological principles but also holds great promise to advance therapeutic strategies related, in particular, to spinal cord injury (SCI). With barely any SCI patients re-gaining complete neurological function, there is a high need to understand how we could target and improve spinal plasticity to re-establish neuronal connections into a functional network.