Functional Neurogenesis

It’s fun to zoom out and get the big picture sometimes. This is one such picture I took long ago when I wanted to see if staining for zinc transporter 3 effectively labels the mossy fiber axons of the dentate gyrus. You can see by the perfect overlap with calbindin that it does the job, though the staining wasn’t quite as bright and obvious as calbindin. The abundance of zinc in mossy fiber axons is one of the peculiarities of the DG and it underlies numerous synaptic properties of DG neurons.

I think the goal was to build on previous work by Lipp, Ramirez-Amaya, and Routtenberg showing that spatial learning causes “sprouting” of mossy fibers, though when I found out that this phenomenon does not occur in mice the project was aborted.

But what else can you see in this picture?

• clear differential expression of calbindin: DG (lots) > CA1 > CA3 (none), and a scattering of strongly-positive interneurons (e.g. 5 cells where CA3 and CA1 meet)
  • in CA1 you can see calbindin is expressed only in the lower band of cells (see hi res photo if needed; there is a ref for this, somewhere)
• a thin band of calbindin-positive fibers crossing the corpus callosum (CC)
• A small group of cells that are not contacted by the calbindin-positive mossy fiber axons (i.e. beyond CA3) yet do not express somatic calbindin (as seen in CA1). I’m guessing this may be mysterious and ambiguous field CA2.

Dendrites are the extensions of neurons that receive incoming information. Neurons have primary dendrites that further split off into secondary and tertiary dendritic branches. On each of these branches are thousands of synaptic connections with axons of neurons carrying incoming information. The result is a dendritic tree that is capable of receiving and integrating a wide array of information within a single neuron. This is one of the neurobiological mechanisms by which different components of a memory are thought to be joined.

Neurons are not born with dendrites and spines – they are acquired during a developmental process that takes many weeks (see here & here). During early development, the pattern of formation of dendrites and spines are sculpted by experience, as might be expected if dendrites and spines are anatomical structures involved in processing and storing sensory information. While a body of work has emerged suggesting adult-born neurons are involved in memory and behavior, no one has yet investigated whether experience is capable of altering the dendritic development of these new neurons. This paper by Tronel et al. is therefore very important because it is the first to look at this phenomenon. They show a dramatic acceleration of dendritic development in response to learning, suggesting a potentially powerful role for new neurons in storing and processing information.
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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 »