So what does this all have to do with stem cells?:

The Hippocampus, Memory and Stem Cells.


You just thought I'd forgotten the topic of this website. No luck, though! The above model describes one type of neural plasticity, one in which all of the neurons are already born, and what changes are the numbers and types of connections. This model probably accounts for the majority of learning. However, there is also a kind of plasticity that appears to relate to adult neurogenesis.


The brain is not uniformly plastic; that is, not all parts of it are equally changeable. The greatest degree of plasticity is found in the hippocampus, a part of the brain that, while it may not store memories per se, appears to control a great deal of the process by which experiences get coded into memories. Damage to the hippocampus does all kinds of screwy things to your memory. In a review of studies on adult neurogenesis, Kempermann (2002) describes the hippocampus this way:

"The hippocampus is classically characterized as the "gateway to memory" but it is clear that the hippocampus is not the 'hard drive' of the brain. Although it has some capacity for memory storage, this storage is transient, and the function of the hippocampus therefore appears to be to prepare contents for long-term storage in the cortical areas. The term "gateway" implies just this: a structure, through which all information must pass, before it can be memorized."

The diagram to the left shows a view of the brain as if you were looking down at the top of someone's head. Their nose would be pointing out from the top of the picture. As you can see, the hippocampus is a relatively small area, which has a fairly complex folded structure. The picture below, to the right, shows another view of the hippocampus' location, this one a side view of the brain.


In addition to having the greatest degree of plasticity in the brain, the hippocampus also appears to be one of the primary sites of adult neurogenesis (i.e., this part of the brain is the one with the most active stem cells). At this point, it doesn't appear that the new neurons have anything to do with storing actual memories--to return to the computer analogy, they don't increase the size of the hard drive. Instead, they appear to increase the ability of the hippocampus to process new information, and to process it in new and more complex ways. It also appears to be related to the need for increased processing ability. Birds and mammals living in enriched environments generate many more new neurons than those in relatively simple ones. For example, Kempermann et al. (1997) kept groups of adult mice in environments with differing complexities of stimuli. At the end of the experiment, the mice in the most enriched environments had greater numbers of neurons in the hippocampus. In addition, they performed significantly better in tasks requiring hippocampal learning.


Similarly, animals that have to navigate complex areas to find food tend to have higher levels of adult neurogenesis than those not requiring that much ability. Patel et al. (1997) studied two groups of adult marsh tits (a type of songbird, shown to the left). Rather than change their environments, the researchers set up the feeding conditions such that one group had relatively frequent, easy access to small amounts of food, and no places available to store excess food. The other group was given much larger amounts of food, every three days, and was allowed to store the food to eat days between eating. Finding places to store food and remembering the locations is generally more difficult than just finding food in obvious locations. The second group, which had to navigate more complex tasks, had a higher rate of neurogenesis in the hippocampus, and an overall greater hippocampal volume.


It appears that there are stem cells present in the brains of most animals (including humans) throughout their life cycles, but that, in animals without constant neurogenesis, they are generally prevented from making new neurons. One question that remains is the role of NMDA. NMDA is a neurotransmitter, one of the chemicals that travels between the axon terminals and dendrites of neurons. It is an excitatory neurotransmitter, which means that it produces a new action potential in the receiving neuron (usually called the post-synaptic neuron). (Inhibitory neurotransmitters stop the postsynaptic neuron from sending signals on). It is also one of the key neurotransmitters associated with Long-Term Potentiation. Thus, without it, normal neuronal plasticity and learning could not occur, and it is present in greater amounts in areas where active learning is taking place. This seems somewhat paradoxical, since that would mean that it increases hippocampal learning ability with pre-existing neurons, but stops new ones from being formed. Since hippocampal learning is also definitely associated with the growth of new neurons, in some species, there must be another factor as yet unexplained. It could be that NMDA plays different roles in different species, or that its downregulating effects are controlled by another circuit we do not understand yet.

There are several other factors that appear to affect neurogenesis and the hippocampus. In birds, the season and hormonal influences seem to be particularly strong influences. For more information on these, see the next two sections:

a. Seasonal influences on neurogenesis

b. Hormonal influences on neurogenesis


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