Learning deficits with age are thought to arise from a progressive loss of synapses and synaptic plasticity, but in vivo evidence has been lacking. In this study we combined in vivo 2-photon microscopy with behavioural assessment and a novel, computer-based, method, called EPBscore, to rigorously track the size (i.e., strength) and location of large populations of synaptic boutons over extended periods of time, and found that:
- Axonal arbors and their boutons continue to remodel in the aged brain.
- The aged cortex shows circuit-specific increased rates of axonal bouton addition, elimination and destabilization.
- Size fluctuations of persistent boutons, believed to encode long-term memories, are larger in the aged brain, while bouton size and density are not affected.
- Increased synaptic destabilization suggests that learning deficits in the aged brain arise because of a higher probability of forgetting rather than a failure to learn.
Figure – Unstable connections. 3D reconstruction of large boutons (light blue) making connections (red) with surrounding cells (grey) in the aged brain.