To die or to sleep, perhaps to dream

Establishing social contacts is the raison d’être of neurons throughout their entire life span. To form and retain functional connections, neuronal differentiation and death are ruthlessly regulated in development and kept strictly under control in post-mitotic systems. Derangements in neural networks affect neuronal populations at large. Therefore, failure to retain synaptic connectivity is linked to dysfunction and often followed by neuronal death. Loss of neurons is a predominant feature of neurodegenerative disease. Nevertheless, neuronal cell death is not an obligate requirement for neural dysfunction at the level of distributed circuits or local circuits. Although more or less wide spread neuronal loss can occur after acute insults such as brain ischemia or invasion of the brain by pathogens, neuronal death is a hallmark of end-stage neurodegenerative and psychiatric disease. The relative contributions made by loss of synaptic connectivity versus cell death for these diseases are still debated. Here these processes are discussed in relation to acute and chronic CNS disorders.