Keystone Symposium on Adult Neurogenesis (2011)

It’s surprising that it’s 2011 and there’s no regular meeting on adult neurogenesis. There have been neurogenesis sessions at other meetings and perhaps the occasional, sometimes closed, neurogenesis meeting here and there, but nothing regular for all to attend. This Keystone meeting on adult neurogenesis will hopefully mark the end of this. About 180 people attended this meeting organized by Jenny Hsieh, Fred Gage, Alejandro Schinder and Pierre-Marie Lledo. The attendees included a large proportion of old and new adult neurogenesis researchers from around the world. And from the scientific program you can see that the interests were diverse, spanning molecular and cellular regulation, anatomy and physiology of new neurons, behavioral functions, clinical relevance and cross-species comparative studies. Data aside, it was also a chance to meet people whose names you’ve seen for years in print but never encountered in the haystack that is SFN. For me, some of these people were long time giants in the field while others were newcomers. A number of people told me they read this blog. And even find it useful!

I didn’t take notes but a number of presentations and themes left an impression. I’ll summarize them in a way that is both brief and poor, so as to minimize any prepublication conflicts:

• Jonas Frisen had some new data using his carbon dating method for measuring adult neurogenesis in humans. From the 10 sec that the slide was up on the screen it looked like he had new data suggesting adult neurogenesis occurs in appreciable amounts in the human hippocampus.
• Grigori Enikolopov presented a novel, interesting (and therefore controversial) story where the radial glial stem cells of the hippocampus each divide rapidly several times and then differentiate into astrocytes, in contrast to the prevailing hypothesis that they are largely quiescent and divide infrequently (his confocal images were absolutely stunning too)
• Gerd Kempermann, using an ablation model, suggested that new neurons are important for reversal learning in the water maze
• Hans-Peter Lipp had a provocative talk on the significance of adult neurogenesis, based on his work in natural populations. He and Irmgard Amrein and collaborators are scouring the globe for the weirdest of mammals, to determine what types of geographical, territorial, social etc factors regulate neurogenesis. Plaguing the natural population field is the same problem found in the human literature (not surprising since humans are a natural population) – analyses only involve endogenous markers of neurogenesis (must it really be this way?) and therefore cannot examine long-term cell addition or fate (such as can be done with BrdU or retrovirus). Regardless, fascinating.
• Amar Sahay / Rene Hen has developed a novel mouse where neurogenesis can be upregulated genetically, apparently avoiding the nonspecific effects seen with usual models of increased neurogenesis (e.g. running, enriched environment).
• Alejandro Schinder‘s work on the physiology of new neurons was impressive because it tackled key questions for understanding what new neurons are capable of doing during behavior. He is looking at the ability of new neurons to associate/integrate inputs (and therefore information) from the lateral and medial perforant paths. He also showed that new neurons in the ventral hippocampus mature more slowly than those in the dorsal hippocampus, which is relevant given the spatial/mnemonic vs. emotional dissociation between these two regions.
• Erno Vreugdenhil provided new evidence that glucocorticoids remain on of the strongest regulators of adult-generated neurons, with glucocorticoid receptor-deficient new neurons displaying profoundly accelerated maturation and abnormal migration
• Martin Wojtowicz presented data from two different hippocampal tasks showing that rats lacking new neurons are more prone to memory interference
• Nora Abrous‘ work reminded us that, while it’s simpler to say that learning enhances neurogenesis, it’s not nearly the whole story (learning also reduces neurogenesis and death of some cells may be required for the survival of others).
• Paul Frankland received too much attention from this blog during SFN so he can take a break here but you’ll notice his website is looking somewhat…blogish. Maybe he can be encouraged to develop it?
• Michael Bonaguidi / Hongjun Song developed an interesting mouse model where they could fluorescently label as few as 2 stem cells in the entire hippocampus, thereby creating an immunohistochemical nightmare. But also enabling a clean look at the asymmetric and symmetric division of these cells and their progeny that is difficult to see in other models where hundreds of cells are dividing in close proximity to one another.
• Adi Mizrahi‘s lab has been monitoring the turnover of new olfactory bulb neurons and their activity in vivo, using 2-photon microscopy and optogenetic approaches. They’ve suggested that even when many months old and fully mature, adult-generated neurons are functionally relevant.
• Tsuyoshi Miyakawa presented some interesting data showing that a number of different mouse models of psychiatric disease share a common feature: an immature dentate gyrus (builds on this paper, which showed that antidepressants, in addition to increasing neurogenesis, “de-mature” mature granule neurons).

Are we spending too much effort studying adult neurogenesis? This was a question I couldn’t help but ask myself during the meeting. Probably a natural feeling when every single talk is on the same topic. But I think it’s valid in spite of this. There was a lot of technically-amazing work presented and it made me wonder if the neurogenesis work is being matched by efforts to understand similar processes in mature dentate gyrus neurons or mature neurons in other neuronal populations. Can we understand the significance of adult neurogenesis if we don’t understand the networks in which they reside? (It’s worth mentioning that some work, e.g. by Schinder’s group, often measures electrophysiological properties of adult-born and perinatal-born neurons, and compares the two. In this way we do learn about both new neuron and general dentate gyrus function)

Is neurogenesis really low in humans? Some presentations of human data and non-human (but long-lived) animals suggested that neurogenesis must be trivial in adult humans. I’m all for being skeptical but I’m not sure this is necessarily the case. The numbers in the Eriksson and Kempermann studies suggest to me that neurogenesis in humans might actually be much more robust than is commonly thought (a topic I’ll write more about soon). Furthermore, differences in neurogenesis across rodent strains and species are great enough that it seems premature to dismiss it in humans based on low numbers in non-human primates.

Where should the field go? The meeting had a great sense of community I thought. Perhaps the only thing missing was some general discussion or consultation about where to go next. Are there certain questions we need to address more than others? For example, one suggestion I heard was that maybe we should spend more time studying neurogenesis in primates, since our comparative knowledge of neurogenesis is weak, our knowledge of primate adult neurogenesis is laughable, and our knowledge of human neurogenesis needs all the help it can get.

Do we need a new diagram illustrating the stages of neurogenesis? Every speaker had their own variant of this image, which usually differed in the shade of grey used to fill the soma of mature granule neurons, or the number of quaternary processes present on radial glia. I therefore spent a few hours on Microsoft Paint and came up with this, which you’re all welcome to use if you ever want to spice things up.

Word has it that if this meeting was deemed successful, there may be another one in 2013. If so, and, barring any major catastrophes in my personal life — see you there.