(very) Young neurons – dying before they ever had a chance?

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.

1-day-old neurons undergoing cell deathYou can clearly see two BrdU-labeled cells (in green; marked with arrowheads) that also express doublecortin (DCX; red). The blue stain, Hoechst, stains DNA allowing for the visualization of all cell nuclei. Collectively, these 3 stains tell us that the cells are 1-day-old (because BrdU was injected 1 day before brains were collected), that they’re neurons (because they express the immature marker DCX) and that they’re dying (because BrdU and Hoechst both label DNA and show that the DNA is condensed in a ball, as is typically seen when cells undergo pyknosis). The arrow points to a lucky, neighboring neuron that is not dying.

Why were these two cells born if they’re only going to die 24 hours later?

I can understand the speculation that neural activity influences the survival of more mature neurons in a “use it or lose it” manner – essentially, if a memory is stored in a young neuron there must be a mechanism to ensure that the neuron, and therefore the memory, survives. But is it possible that a similar mechanism also influences the survival of very immature neurons? It’s hard to imagine, since very young neurons do not have synapses and cannot participate in memory processing/storage. Consistent with this idea, Tashiro has shown that NMDA receptors (a synaptic ingredient essential for many forms of memory) regulate the survival of 2-3 week-old neurons, which are just beginning to form synapses, but not younger neurons that have not yet formed synapses. However, the possibility remains that learning could do something to these 1-day-old neurons – e.g. epigenetically imprint them – so that they have some sort of cellular memory that causes them to subsequently participate in certain behaviors but not others. Since information is typically thought to be stored at synapses, I can’t imagine that these memories could be terribly specific but they could bias a young neuron to be more involved in a general class of behavior (e.g. spatial memory vs. stress) that is associated with certain broad differences in activity (e.g. firing patterns, neuromodulators, hormones). It would be really cool if someone shows this.