Inserting new synaptic connections into damaged neural circuits: towards synapse therapy?

Recovery from neural damage often requires reorganization of remaining neural tissue, including the formation of new synaptic connections between surviving neurons. Such rewiring may restore disrupted information flow caused by neuronal loss, and help adjust altered neural circuitry to reestablish diminished functionality. On occasion, proper rewiring may occur spontaneously, leading to successful recovery (Joy and Carmichael, 2021). However, in many cases natural rewiring is insufficient, and may even cause maladaptive deterioration due to miswiring (Nava and Röder, 2011). To overcome this, several interventional strategies have been developed to assist in the recovery process, by guiding synaptic rewiring in desirable directions (Su and Xu, 2020). For example, enhanced usage of the affected limbs or the impaired mental capacities can stimulate proper activitydependent rewiring (Ganguly and Poo, 2013). Pharmaceutical targeting of specific molecular pathways (Joy and Carmichael, 2021) can bolster desirable plasticity processes and suppress unwanted ones. Cell-based therapy (Wechsler et al., 2018) can increase neurogenesis, replacing missing neurons and giving rise to new network connections. BrainMachine Interfaces can serve as artificial communication pathways within the nervous system or between neurons and artificial effectors in order to bypass broken l inks in disrupted networks and establish new prosthetic neuronal connections (Wolpaw et al., 2020).

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