Adult neurogenesis. From circuits to models.

Our understanding of the hippocampus as a memory-encoding device is greatly helped by our knowledge of neuronal circuits and their plasticity. The trisynaptic hippocampal circuit carrying afferent input from the entorhinal cortex, controlled by a network of inhibitory interneurons and supplemented by modulatory subcortical inputs forms a platform for multiple forms of synaptic plastic mechanisms. Long-term potentiation of synaptic transmission in its various forms is an outstanding example of hippocampal ability to adapt to past neuronal activity. Adult neurogenesis is a profound plastic mechanism incorporating structural and functional changes that were previously thought to be present only in developing neural systems. These powerful forms of plasticity can mask experimental results by compensating for experimentally induced changes in the neurons or circuits. Circuit lesions have been one of the most common techniques in scientific investigations of the hippocampus. Although the effects of such lesions can be quite revealing and ground-breaking, in many cases the results are masked by compensatory mechanisms producing misleading results. This review will highlight such mechanisms and argue that the experimental results, in spite of their shortcomings, can be better understood when viewed in light of our knowledge of the neuronal circuitry, and with guidance by conceptual and computational models. Studies demonstrating a role of neurogenesis in pattern separation and memory interference are a good example of fruitful interaction between modeling and experimental approaches.