ReviewUse it or lose it: How neurogenesis keeps the brain fit for learning
Highlights
► Neurogenesis and learning interact to maintain a fit brain. ► Learning increases the survival of new neurons if it is difficult to achieve and successful. ► Learning increases the survival of new neurons only during a critical period in cell maturation. ► Immature neurons are seemingly used for some types of complex learning. ► Immature neurons might be recruited into existing neural networks via oscillatory activity.
Introduction
Thousands of new neurons are added into the adult hippocampus each day. However, most of the new cells do not survive. In fact, over half of them, if not more, die within just a few weeks of their birth. One of the most effective ways to keep these cells from dying is by learning. Animals that learn a new and difficult task retain more of these new cells than animals that do not learn or learn a very easy task [1], [2], [3], [4]. Thus, effortful and successful learning keeps new neurons alive. Moreover, once rescued, the new neurons survive for months at least [5]. These new cells establish anatomical connections with other neurons, which not only affect neuronal activity within the hippocampus but also presumably affect synaptic and neuronal activity at efferent locations throughout the brain.
The evidence that new neurons might be influenced by learning and perhaps even involved in learning was not initially well accepted [1], [6], [7]. Of course, we do not fully understand how learning occurs much less which neuroanatomical and neurophysiological processes are necessary. However, prior to the discovery of neurogenesis, it seemed prudent to assume that learning and the consequent establishment of memory would use already existing neurons and then change the synaptic connections between those neurons as a result of learning—at the so-called Hebbian synapse [8]. This was and still is the prevailing notion behind most neurobiological theories of learning [9]. It is probably in large part correct. However, we must now incorporate the idea of new neurons into the system. Are they involved or just casual by-standers? Are they necessary or simply modulators? Why does the brain produce these new neurons and how does it optimize the number of new ones so that they are useful but not disruptive? In this review, we will address these questions and propose a positive feedback system between neurogenesis and learning. Within this system, learning increases the survival of the new neurons in order that they may then be used to learn more efficiently in the future.
Section snippets
How many is enough?
The number of new cells produced in the hippocampus is estimated to be about 10,000 per day in young adult male rats [10] and around 3500 in older adult male rats [11]. Similar numbers or more are expected in humans [12], [13]. This seems like a rather large number in isolation. However, one rat dentate gyrus (DG) possesses about one million mature granule cells [14]. In this context, several thousand each day is not so many. As they continually accrue, the adult-born new neurons still only
Use them or lose them
The good news is that new neurons are produced throughout adulthood. The bad news is that most of them do not survive. More than half of the new cells die within just a few weeks of being born. The death of so many new cells seems like a tremendous waste of energy and leaves one wondering about the functional significance of new neurons. Why would they be produced if only to die weeks later? What happens to the ones that do not die and how can more be encouraged to survive? It turns out that
Learning with ease
While some forms of learning can increase neuronal survival, others seem to have no such effect. For example, training with delay eyeblink conditioning does not increase the number of neurons that survive [1]. Why is it that the acquisition of trace, but not delay, eyeblink conditioning increases neuronal survival? Until quite recently, we hypothesized that tasks that require an intact hippocampus would rescue new neurons from death whereas tasks that do not depend on the hippocampus would not.
Using them
From the moment of their discovery, new neurons were implicated in learning. This was in part because the hippocampus is involved in many processes related to learning and even necessary for a subset of those processes. The hippocampus is most often associated with spatial learning because removal of the hippocampus results in deficits in learning about spatial cues in the environment. The most often used task to assess spatial learning is the Morris water maze task [41]. During training, the
Learning to learn
In isolation, the new cells may not seem that distinct from those generated during early gestation and postnatal development [70], [71]. However, there are several key differences. Perhaps most importantly, they mature within a population of mature cells with established connections. As a consequence, they can receive synaptic input almost as soon as they are generated and can therefore do so as they are developing [39], [72], [73]. This input affects their survival and fate. As discussed,
Critical periods of time
Adult-born neurons tend to follow the same stages of development, as do cells in the young, immature brain. However, the emergence of synapses requires a bit more time [78]. Adult-born cells in the DG extend their axons into the CA3 by the end of the second week of their life and produce dendritic spines and functional synapses with other cells in about 3 weeks [78]. Presumably, these connections are guided by pre-existing synapses within the surrounding local neuronal network in the DG [23].
Out with the old, in with the new—the role of new neurons in learning
Early on, we proposed that new neurons are used to encode the timing of events or the timing of responses [7]. This idea arose in part because the new cells are so responsive to learning the temporal relationship between very closely occurring stimuli: Exposure to a training regime that requires the animal to learn to time its responses within just a few tens of milliseconds in the framework of stimuli that last up to seconds increases the number of new adult-born cells that survive [27].
Communication is key
When new neurons were first discovered, it was necessary to evaluate them exclusively. This approach provided us with an abundance of information about the cells and their development. However, now that we know as much as we do, it is time to consider them in their context. To process external input, the brain works as a whole, based on spatially distributed but functionally related networks of cell assemblies. One fairly convincing view of how cell assemblies scattered throughout the brain
Use and misuse
It is of course encouraging to know that our brains continue to produce new neurons throughout our lives. It is even more encouraging to know that we can make more of them by engaging in healthy behaviors and we can keep more of them by engaging in serious mental activity. However, the pendulum can swing the other way—with bad behaviors and minimal mental activity, fewer cells will be produced and even fewer will survive. One or two days or even one or two months may not be enough to affect the
From muscles to memories
The phrase “use it or lose it” is used most often to refer to the relationship between exercise and muscle mass. In this case, the cells themselves become larger after exposure to physical stimulation and strenuous activity. Once enlarged, they integrate more readily with other muscles to form functional muscle circuits. As a consequence, motor activities and skills that were once difficult if not impossible to do can now be accomplished with ease. In this way, the analogy to neurogenesis is
Acknowledgements
This work was supported by the National Institutes of Health (grant nos. MH-59970 and ARRA-3R01MH059970-10S1) and the National Science Foundation (grant nos. IOB-0444364 and IOS-0914386) to T.J.S. This work was also supported by grants from the Academy of Finland, Emil Aaltonen Foundation, and Jenny and Antti Wihuri Foundation to M. S. N.
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- 1
Permanent address: Department of Psychology, University of Jyvaskyla, Jyvaskyla, Finland.
- 2
Address: Department of Neuroscience, Rutgers University, Piscataway, NJ, 08854, United States.