Differential robustness of neural networks in a regenerative brain

While we often consider the complexity of information processing in a nervous system, the robustness and resilience of the signaling network is critically important following brain injury and subsequent plastic remodeling. These concerns are especially relevant in the flatworm Schmidtea Mediterranea, a planarian which regularly regrows an entire brain and central nervous system during fissioning asexual reproduction. Here, we develop a platform to continuously measure planarian behavior throughout neural regeneration. We demonstrate that planaria are capable of information processing including signal integration, short term memory, and latent arousal states. Surprisingly, sensitization (a form of short-term memory), is retained even after brain amputation, whereas other memory like habituation do not return until late neural development . To understand the asynchronous return of function, we performed a genetic knockdown screen and found that sensitization and arousal require relatively long-range diffusive neuropeptide signals, while suppression of activity depends on locally-acting synaptic monoamines. Our results show that longer range peptidergic transmission creates a signaling network more robust to structural perturbations than the traditional synaptic connectome.