REWIRING OF THE ADULT HIPPOCAMPAL PROJECTOME IMPROVES MEMORY

A process by which cognitive training, meditation, or mindfulness can improve aspects of daily life is often referred to in popular parlance as “brain rewiring”. Despite the widespread use and presumed beneficial effects of this process, the biological underpinnings and the basic question of whether brain rewiring in the literal sense, i.e. axonal rewiring, can improve cognitive function remain entirely open. Here we investigated axonal rewiring in healthy adult mice and in the context of memory. To rewire hippocampal pyramidal neurons, we used the transcriptomic regulator Id2 as an inducer of adult neuronal wiring. Unexpectedly, Id2 not only induced axon growth in pyramidal neurons and increased their synaptic output to their target areas, including the subiculum, lateral septum, amygdala, and prefrontal cortex, but also rejuvenated the cells’ action potential firing from the slower adult rate to the faster juvenile rate. As a result, the neurons could broadcast more content at a higher bandwidth. Notably, these synergistic effects improved working memory, long-term memory, and remote memory retrieval in spatial and object-related tasks. Taken together, our results demonstrate that the adult brain has unused capacity to accommodate additional neural connections, and that brain rewiring can improve brain function.