Disassembly and rewiring of a mature converging excitatory circuit following injury

Specificity and timing of synapse disassembly in the CNS are essential to learning how individual circuits react to neurodegeneration of the postsynaptic neuron. In sensory systems such as the mammalian retina, synaptic connections of second-order neurons are known to remodel and reconnect in the face of sensory cell loss. Here we analyzed whether degenerating third-order neurons can remodel their local presynaptic connectivity. We injured adult retinal ganglion cells by transiently elevating intraocular pressure. We show that loss of presynaptic structures occurs before postsynaptic density proteins and accounts for impaired transmission from presynaptic neurons, despite no evidence of presynaptic cell loss, axon terminal shrinkage, or reduced functional input. Loss of synapses is biased among converging presynaptic neuron types, with preferential loss of the major excitatory cone-driven partner and increased connectivity with rod-driven presynaptic partners, demonstrating that this adult neural circuit is capable of structural plasticity while undergoing neurodegeneration.

Automated summary

The specificity and timing of synapse disassembly in the CNS are crucial for understanding how individual circuits respond to neurodegeneration of the postsynaptic neuron. Synaptic connections can remodel and reconnect in sensory systems like the mammalian retina after sensory cell loss. In this study, it was found that adult neural circuits are capable of structural plasticity while undergoing neurodegeneration, with loss of synapses biased towards certain presynaptic neuron types.