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

Increased neurogenesis is not (necessarily) the opposite of reduced neurogenesis


Two recent papers have attracted a lot of media attention because they draw direct links between adult neurogenesis and behavioral disorders: Noonan et al. showed that rats lacking adult neurogenesis (stopped with irradiation) are more susceptible to cocaine addiction. Jin et al. showed that mice lacking adult neurogenesis (using a transgenic model) suffer greater infarct size and have more severe motor deficits after stroke.

While the papers themselves have important implications, what caught my attention was the angle taken by press releases: both articles studied the effects of reducing neurogenesis but the media focused on potential benefits of increasing neurogenesis. See speculation that antidepressants, by increasing neurogenesis, might be stroke-protective here. And, from Science Daily:

While the research specifically focused on what happens when neurogenesis is blocked, the scientists said the results suggest that increasing adult neurogenesis might be a potential way to combat drug addiction and relapse.

It may very well be the case that increasing neurogenesis is good in the same way decreasing neurogenesis is bad but it shouldn’t be assumed – maybe we have all the neurogenesis we need and, while completely arresting neurogenesis could be harmful, increasing neurogenesis beyond normal levels is just redundant. Continue reading Increased neurogenesis is not (necessarily) the opposite of reduced neurogenesis

The first example of functional neurogenesis?

ResearchBlogging.org I recently became re-acquainted with the neurogenesis literature while writing the last post, re-finding data in papers whose gist, but not details, I had remembered. I reached out a little bit, asking others if I had forgot any studies and indeed I had, including this study by Okano, Pfaff and Gibbs from 1993.

I’ve been interested in new neuron function since 1999 and so I’m actually quite surprised I missed this study until so recently. In 1999 the neurogenesis literature was so scant that it was easy to know ALL of the studies, even the early Altman, Kaplan and Nottebohm studies from the 1960s through 1980s. Even studies that were not interesting were interesting, because there was nothing else to read! So, had I known about it back then, I would have been pretty interested in this study by Okano et al. if only for its focus on cell cycle markers. But I really would have been interested in it because it has a small functional experiment that was way ahead of it’s time:

Continue reading The first example of functional neurogenesis?

Everything you always wanted to know about neurogenesis timecourses (but were afraid to ask)

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

addition of new neurons

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.

Continue reading Everything you always wanted to know about neurogenesis timecourses (but were afraid to ask)

Adult neurogenesis in humans: Murine Features of Neurogenesis in the Human Hippocampus

Studies of adult neurogenesis often begin with the following sentence: “Adult neurogenesis occurs in all mammals examined, including humans.” More detail-oriented papers might say, “Adult neurogenesis occurs in all mammals examined, including humans…but not bats.” Here, the similarities between bats and humans become more evident than one might expect: it could be an equally long time before we understand adult neurogenesis in either of these species. Bats are (relatively) easy enough to study experimentally, but how many studies will be required to understand why neurogenesis does not occur in the adult bat brain? With humans, we have the opposite problem: the one study in humans that used the unambiguous cell-birth marker, BrdU, found adult neurogenesis. The second study may never exist. Continue reading Adult neurogenesis in humans: Murine Features of Neurogenesis in the Human Hippocampus

Decade in review #1: the neurogenesis-depression hypothesis

psa-ncam banner

At 0.6% of the way into the decade, we’re well beyond the timeframe when most “things of the decade” articles appear. Now that “decade hype” has settled down I thought it would be fun to write a series of posts that discuss some of the major themes in adult neurogenesis over the last decade. A lot has happened in this time; depending on how you birthdate the field (i.e. not counting the work of Joseph Altman), the last decade represents over half the lifetime of the field. BDHXV8966V35

One very influential theme that emerged, only to gain momentum, is the neurogenesis-depression hypothesis. Generally, the idea is that adult hippocampal neurogenesis is protective against depression. This idea was initially quite novel because, 10 years ago, most people were fixated on the hippocampus as a structure involved in learning and memory. Indeed, it’s not implausible that the ability to form rich, detailed memories (which the hippocampus is known for) could enable one to make associations and see perspectives that allow them to escape a depressive funk. But more direct evidence linking the hippocampus to mood has come from studies showing that manipulations to the hippocampus alter stress and anxiety-related behaviors. Continue reading Decade in review #1: the neurogenesis-depression hypothesis

A list of experiments that relate adult hippocampal neurogenesis to behavior

The list as a Google spreadsheet (also excel | HTML | RSS feed of updates)
List last updated 3/9/2011.

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? Continue reading A list of experiments that relate adult hippocampal neurogenesis to behavior

Cell Nov. 13, 2009: Adult Neurogenesis Modulates the Hippocampus-Dependent Period of Associative Fear Memory

Adult Neurogenesis Modulates the Hippocampus-Dependent Period of Associative Fear Memory

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. Continue reading Cell Nov. 13, 2009: Adult Neurogenesis Modulates the Hippocampus-Dependent Period of Associative Fear Memory

New neurons in the adult brain. How they work and what they're good for.