The divergence–convergence model of acquired neuroprotection

It is commonly known that mental activity helps to maintain a healthy brain. Recent research has unraveled the underlying molecular mechanisms that explain why an active brain lives longer. These mechanisms involve the activation of a comprehensive transcriptional program that is triggered by enhanced synaptic activity and renders neurons resistant to harmful conditions. Functionally, this state of acquired neuroprotection may be achieved mainly via one mechanism, which is the stabilization of mitochondria. In this review we propose a model that describes the signaling network that links synaptic activity to neuroprotection. We suggest that the divergent-convergent architecture of this signaling network ensures both robust and reliable as well as persistent activation of the neuroprotective machinery.

► Enhanced synaptic activity renders neurons resistant to harmful conditions. ► This ‘acquired neuroprotection’ involves the activation of a large gene network. ► Activity-regulated pro-survival genes act to preserve mitochondrial integrity. ► A divergent–convergent signaling network links neural activity to neuroprotection. ► Our model might help explain central features of acquired neuroprotection.