Functional Neurogenesis

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.

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I’ve always enjoyed making lists. As a kid I can remember writing lists of rhyming words, lists of all the Ocean Pacific clothes I owned, lists of all the people I knew. Many years later, I hope I’ve now made a list that is actually useful.

Adult neurogenesis is now undisputed. Pretty much on a weekly basis there is a new paper that examines both levels of adult hippocampal neurogenesis and behavior, attempting to draw a functional connection. The good news is that the argument for a behavioral function for adult neurogenesis continues to get stronger. The bad news is that there’s a massive pileup of data, and it’s becoming hard to filter through the relevant studies – first you have to find them amongst the 1000+ studies of adult neurogenesis. Then you have to read them. What behaviors are examined? Is there an effect of reducing or enhancing neurogenesis? What method is used to manipulate neurogenesis? What do other studies find that performed a similar analysis? Read the rest of this entry »