Adult neurogenesis and hippocampal memory function: new cells, more plasticity, new memories?

Abstract

The discovery of active adult neurogenesis in mammals, a process of generating functional neurons from neural stem cells, suggests that the adult brain is more dynamic than once imagined. The coincidence of this phenomenon occurring in the hippocampus, a region critical to the learning process, begs the question of whether adult neurogenesis is involved in memory formation. Here, the authors review rapidly accumulating evidence showing a strong correlation between certain types of memory functions and adult neurogenesis in the hippocampus. Establishment of the potential link between memory formation and adult neurogenesis is instrumental, at a basic science level, to understand the function of neural networks and is essential, at a clinical level, to develop effective therapies for various cognitive dysfunctions.

Fig. 1

DG neurogenesis incorporation of new neurons. Neurogenesis in the hippocampus occurs in the SGZ of the DG, wherein neural progenitor cells reside (1). Within the first week after birth, these progenitors undergo a fate choice, in this case, becoming an immature neuron (2) with developing neurites. The axons of these new granule neurons are guided through the hilus of the DG, with long-distance branches targeting the CA3 (3) and the dendrites extending into the molecular layer (3). After 3 to 4 weeks, these cells form a mature phenotype, with their dendrites containing spines that receive input primarily from the entorhinal cortex (EC) by way of the perforant pathway (red axon) and their highly branched axons that output to CA3 pyramidal neurons (4) and hilar mossy cells (MC) by way of the mossy fiber pathway (green axon). Continuing the hippocampal circuitry, the CA3 pyramidal neurons output to the CA1 ipsilateral pyramidal neurons by way of the Schaffer collateral pathway or contralaterally by way of the associational commissural pathway (blue axon). The CA1 pyramidal neurons output (orange axon) to pyramidal neurons of the subiculum (SB), which output (cyan axon) to the EC, and these neurons eventually output to the parahippocampal and perirhinal cortex. Ultimately, the circuitry connects to the association cortices.

Fig. 2

Theory of hippocampal neurogenesis in learning and memory. In normal neurogenesis (B), it appears that new neurons are constantly replacing a small portion of the existing population at a basal rate without a significant overall increase in the number of total granule neurons in the DG over time. Under certain conditions that cause a decrease in neurogenesis (A), it is assumed that this rate of replacement is significantly decreased and that with stimulation, this rate of replacement increases (C). Compared with the mature neuron population, the proportion of new neurons may cause a shift into an elevated plastic state. An increase in neurogenesis, and thus an increase in plasticity, may cause improvement in learning and memory tasks. Therefore, conversely, blocking neurogenesis and decreasing the plasticity index may be the cause of the observable decline in performance with various learning- and memory-related tasks.