Functional Neurogenesis

A fundamental property of the hippocampus is its ability to rapidly encode memories while simultaneously keeping them distinct. Recording from hippocampal neurons one can clearly see that different populations of neurons are active as a rat explores two environments. This is thought to be one mechanism by which information is kept distinct in the brain.

For the last 15-20 years it has been thought that the dentate gyrus (DG), a major subfield of the hippocampus, serves to take small changes in incoming sensory information and orthogonalize them (i.e. make them more different). This idea was built in part on the fact that there are many more DG neurons than upstream cortical neurons. Thus, the DG could use completely different populations of neurons to represent different sets of incoming information and then pass on these representations to CA3, which may bind them into coherent events/memories (the interconnectedness of CA3 neurons, via “recurrent collatorals”, is thought to be a mechanism by which the different components of a memory are bound together).

However, a “problem” arose when Leutgeb et al. found that it is always the same population of dentate granule neurons (~1% of the total population) that are active as an animal explores different environments, even very different ones. This was a bit of a surprise. Still consistent with the proposed role of the DG in orthogonalizing information, however, was the fact that the DG neurons fired (i.e. generated action potentials, which transmit information from neuron to neuron) at different rates/frequencies in the different environments. Thus, changes in sensory information were represented by changes in patterns of activity within the same population of cells, not by recruiting different populations of cells. This is but one study – the question of how the DG encodes and extracts information is far from settled (e.g. what are the other 99% of granule neurons doing? Surely there is a situation in which they are active, no?). But the findings were robust and raise many questions, namely: How does the same population of DG neurons activate different populations of downstream CA3 neurons, during different experiences? Read the rest of this entry »

Yesterday I was taking pictures of 1-day-old neurons, which was irritating me for several reasons. First, at this age they’re small, irregular and uglier than the mature neurons I’m used to examining. Second, very immature neurons are located amongst a mess of proliferating cells and fellow young neurons so it becomes hard to discern one cell from the next.

One positive thing that came out of looking at these very immature neurons was that I got the chance to see several examples of pyknotic (dying) cells. Older, adult-born neurons also die, particularly after an experience (see here and here), but it’s infrequent and hard to visualize. However, a relatively large proportion of new neurons die within a few days of their birth making them easier to find – the cluster of cells shown below is an example that caught my attention.

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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 »

Kitamura et al. (2009) Adult Neurogenesis Modulates the Hippocampus-Dependent Period of Associative Fear Memory. Cell. 139:814-827.

It’s great to see this paper finally in print. At SFN 2008 the authors had a poster that generated a lot of excitement, at least in our circles.  And the poster was quite a sight: there was such a profusion of data that the poster poured off the easel, nearly reaching the floor. With 27 (!) supplemental figures in the final article, one has to wonder if this is the final straw that led to this article.

The authors use an ingenious approach to address an idea that has been floating around for a while: that adult neurogenesis regulates memory turnover in the hippocampus. Read the rest of this entry »