Biology does an insane amount of packing and shipping in these spaces already and this is the stick against which we should measure potential modifications. Whi

Biology does an insane amount of packing and shipping in these spaces already and this is the stick against which we should measure potential modifications. While a neuron is active, vesicles will be riding up and down the axon tubules, shepherding RNA and building blocks, releasing and reuptaking neurotransmitters, and dozens of ion-selective transports create the electrical behavior. At the cellular level, the brain has its own immune system, at the tissue level it has the blood-brain barrier. This is all neuron-specific innovation, everything from basic cell biology still applies. The point is: if you are familiar with the biology, you are familiar with a dozen transport systems (and can infer the likely existence of a hundred mechanisms) more sophisticated than waste evacuation and none of them require the neuron to go offline, so the prospect that this is the hangup seems unlikely. Also, the complexity of transport scales with the system. Famously, zebrafish don't need a functioning heart for the first week of their life because at that stage they are small enough that diffusion does a good enough job transporting nutrients and oxygen. Needless to say, this goes for waste evacuation as well: small size trivializes the problem. Nematodes are even smaller that zebrafish, yet they still sleep. "Sleep is about training neuron functionality" explains the universality of sleep much better than "cleaning is hard."