Use it or lose it: how neurogenesis keeps the brain fit for learning

Abstract

The presence of new neurons in the adult hippocampus indicates that this structure incorporates new neurons into its circuitry and uses them for some function related to learning and/or related thought processes. Their generation depends on a variety of factors ranging from age to aerobic exercise to sexual behavior to alcohol consumption. However, most of the cells will die unless the animal engages in some kind of effortful learning experience when the cells are about one week of age. If learning does occur, the new cells become incorporated into brain circuits used for learning. In turn, some processes of learning and mental activity appear to depend on their presence. In this review, we discuss the now rather extensive literature showing that new neurons are kept alive by effortful learning, a process that involves concentration in the present moment of experience over some extended period of time. As these thought processes occur, endogenous patterns of rhythmic electrophysiological activity engage the new cells with cell networks that already exist in the hippocampus and at efferent locations. Concurrent and synchronous activity provides a mechanism whereby the new neurons become integrated with the other neurons. This integration allows the present experience to become integrated with memories from the recent past in order to learn and predict when events will occur in the near future. In this way, neurogenesis and learning interact to maintain a fit brain.

Figure 1. Successful and effortful learning increases the survival of adult-born hippocampal neurons

A) Animals that successfully learned the conditioned response (Good Learners) retained significantly more cells than those that failed to learn (Poor Learners), or those that were not trained with paired stimuli (Unpaired). Animals that failed to learn displayed no increase in the number of surviving cells. Thus, learning only increases the survival of new neurons when that learning is successful. B) Of those animals that learned, those that took longer to do so emitted fewer conditioned responses (CRs) over the course of training. However, those animals that took longer to learn retained more new cells than those that learned in relatively few trials. Representative BrdU-labeled cells from the granule cell layer of (C) an animal that successfully learned trace eyeblink conditioning and (D) an animal that failed to learn (Curlik & Shors, 2011).

Figure 2. Suppressing neurogenesis with an anti-mitotic agent suppresses associative learning of a trace memory but does not suppress spatial learning in the Morris water maze

A) Animals treated with the anti-mitotic agent MAM generated very few new neurons and B) most of them were unable to learn the trace memory (Shors et al., 2001). C) Animals treated with the anti-mitotic agent generated very few new neurons but D) readily learned to find the hidden platform using spatial cues in the environment (Shors et al., 2002). Therefore, suppression of neurogenesis is associated with deficits in some but not all types of learning processes.

Figure 3. A model of integration of adult-born immature neurons into functional networks within the dentate gyrus (DG)

We propose that when a novel event occurs, oscillatory activity, that is, synchronous firing of existing mature neurons in response to that event engages immature neurons to also fire in synchrony. These cells are thus recruited into the network. Immature neurons might be especially receptive because of their heightened excitability. At the level of the local field potential, joint activity of both mature and immature neurons would be manifested as increased synchrony and response magnitude. The new neurons might thereby enhance the quality of the output by improving both short (milliseconds) and long (days, months, years) term temporal coding. Eventually, the new neurons would survive because of their participation in the network activity. Once rescued from death, they would mature into neurons and participate in new learning related to the initial learning experience.