As we accumulate more and more data on adult neurogenesis in rodents I keep asking myself what kind of impact these new cells could have. The dearth of literature on primate and human adult neurogenesis seems to make these questions all the more relevant. As a starting point, I created a Pubmed collection of all the studies of adult hippocampal neurogenesis in humans. They’re also listed below in a Google spreadsheet. Note that human studies often do not directly measure neurogenesis but instead measure 1) cell proliferation (which usually correlates with neurogenesis in rodents, but assumes that proliferation results in surviving neurons in humans), 2) stem cell markers (such as nestin, which correlates with neurogenesis only if they indeed divide and produce new neurons), 3) immature neurons (which, technically speaking, is neurogenesis, but whether these neurons mature and become functional remains to be determined), or 4) other factors that correlate with neurogenesis, such as blood flow or stem cell biomarkers. So, while the conclusions of these studies may be exciting (or depressing), they have to be taken with a grain of salt at this point.
Most studies of adult neurogenesis are concerned with neuronal age. Or at least they should be. This is because new neurons develop from a stage where they have no excitatory synapses to one where they have many. If we assume the traditional view that information is stored at excitatory synaptic connections, then young neurons are initially useless and only become physiologically and behaviorally meaningful when they have matured to a point where they can relay and process information. It is therefore critical that the developmental timecourse of new neurons be mapped out, so we know when new neurons become functionally relevant, or whether they might even have different functions at different ages.
Below are what I hope to be comprehensive visual collages of all published timecourse experiments, where a certain property of new neurons is examined at multiple (≥ 3) different ages. They are grouped by studies of: 1) cell survival, 2) marker expression, 3) functionality, and 4) miscellaneous studies that do not quite fit into the first 3 categories. I’ve ordered the data roughly chronologically and have included the first author’s name and publication year so you can read deeper, if needed. Indeed, if you know these studies already, a brief look at the graphs will bring back the take home message. However, since the data is stripped of text, if the studies are unfamiliar, you’ll have to go to the original source to figure out what the heck they mean (use Pubmed to at least obtain abstracts for the original studies if I didn’t provide a direct link).
Personally, I like timecourse studies for the same reason I like to have all my music albums or books visible at the same time: at a single glance they provide a lot of information – each individual stage of maturation can be interpreted within a bigger picture. The result of these many hours of work will either be a) that the purpose of adult neurogenesis will become immediately clear, or b) that we’ll all have some fancy collages to pin on our bulletin boards and look intelligent.
The survival timecourse
New neurons are born and then many die. The survival timecourse answers the questions: How many new neurons are born? Where are they born and where do they end up, anatomically? How many of them survive and can their survival be altered? Survival timecourses are typically performed by injecting animals with a mitotic marker that will label new neurons as they’re being born, e.g. ³H-thymidine (old school), BrdU (tried and true – example), or a GFP-expressing retrovirus (new school). At a later date one can then detect these birthdated new neurons and count them, see where they’re located etc.