Proper wiring of newborn neurons to control bladder function after complete spinal cord injury

Activation of endogenous neurogenesis by bioactive materials enables restoration of sensory/mor function after complete spinal cord injury (SCI) via formation of new relay neural circuits. The underlying wiring logic of newborn neurons in adult central nervous system (CNS) is unknown. Here, we report neurotrophin3-loaded chitosan biomaterial substantially recovered bladder function after SCI. Multiple neuro-circuitry tracing technologies using pseudorabies virus (PRV), rabies virus (RV), and anterograde adeno-associated virus (AAV), demonstrated that newborn neurons were integrated into the micturition neural circuits and reconnected higher brain centers and lower spinal cord centers to control voiding, and participated in the restoration of the lower urinary tract function, even in the absence of longdistance axonal regeneration. Opto- and chemo-genetic studies further supported the notion that the supraspinal control of the lower urinary tract function was partially recovered. Our data demonstrated that regenerated relay neurons could be properly integrated into disrupted long-range neural circuits to restore function of adult CNS.

Automated summary

Activation of endogenous neurogenesis using bioactive materials can restore sensory/motor function in complete spinal cord injury patients through the formation of new neural circuits. The wiring logic of newborn neurons in the adult central nervous system remains unknown. This study demonstrated that neurotrophin3-loaded chitosan biomaterial effectively restored bladder function after spinal cord injury. The use of neuro-circuitry tracing technologies revealed that newborn neurons were integrated into micturition neural circuits and reconnected brain and spinal cord centers for voiding control, facilitating the restoration of lower urinary tract function.