Neurogenesis and the septotemporal axis at #SFN11

As I’ve alluded, science, and therefore the SFN meeting where much science is unveiled, is a cycle of confusion and clarification. Currently, confusion may be prevailing in the adult hippocampal neurogenesis field since new neurons have been implicated in everything mammals do – spatial and nonspatial memory, anxiety, depression, addiction, social behavior, stress regulation, blinking etc. This should not be entirely surprising since the hippocampus itself, where these young neurons reside, has many different functions. But how can we reconcile these seemingly disparate functions?

Every time I get worked up about all these neurogenesis findings I think about two words that return me to a state of inner peace, calmness, and….mental turmoil that all of my experiments will have to be performed twice: Septal and Temporal. Neurogenesis aside, the septal and temporal ends of the hippocampus are connected to different brain structures that cause the septal hippocampus to be more involved in spatial processing/cognition and the temporal hippocampus to be more involved in regulating stress and emotion. Which has the potential to explain everything.

Two posters today did a great job of analyzing neurogenesis in these different parts of the hippocampus and relating these findings to function. First, Tanti et al. showed that while a chronic stress model of depression reduced neurogenesis along the entire septotemporal axis, the antidepressant fluoxetine (aka Prozac) rescues this deficit specifically in the temporal hippocampus. In contrast, environmental enrichment, which may be viewed as more of a spatial and cognitive stimulus, selectively (and massively!) increased neurogenesis in the septal hippocampus with no effect in the temporal hippocampus. A nice dissociation where different classes of stimuli (drugs that regulate emotion vs. knowledge about objects and environments) regulate plasticity in different parts of the hippocampus.

This was complemented by a thorough study by Lehman et al., who recently showed that new neurons aid in the recovery from psychosocial stress, they asked whether “depressed” mice that suffered social defeat showed regional differences in neurogenesis. The prediction would be that neurogenesis should be specifically reduced in the temporal hippocampus, since this is the region that regulates the stress and emotional responses. They too were curious about the effects of environmental enrichment, since they’ve previously found that enrichment can rescue mice from a depressed state, but only if neurogenesis was present. The story sounds complicated when I tell you that they did all these experiments in normal mice and mice that had their adrenal glands removed, and had low levels if stress hormones (glucocorticoids). But a surprisingly clear picture emerged:

Social defeat (getting beaten up by a big bully mouse and then having to constantly live next to him) increased glucocorticoids and led to anxiety/depressive behaviors. Furthermore, social defeat specifically reduced neurogenesis in the temporal (i.e. “emotional”) hippocampus. The culprit was glucocorticoids – by removing glucocorticoids both the “depression” and neurogenesis impairments could be reversed. In a complementary experiment, they found that environmental enrichment is also a stressor, but a good stressor. Environmental enrichment increased glucocorticoids yet its other effects were beneficial – the mice were less anxious, less depressed, and they had increased neurogenesis. And just as with social defeat, the effects of environmental enrichment were also dependent on glucocorticoids: when glucocorticoids were removed, environmental enrichment did not reduce anxiety/depression and it did not increase neurogenesis.

The take home message is that stress hormones have bad effects on behavior and neurogenesis in the context of social stress, but they have good effects on behavior and neurogenesis in the context of environmental enrichment. And while we don’t yet know if septal neurogenesis is more important for spatial/cognitive behaviors and temporal hippocampus for emotional regulation, both of these posters did a great job of convincing me that this is a direction we need to pursue if we are to understand the many functions of new neurons. They also made it clear that there are complex interactions between stress, neurogenesis and behavior. To the point that I can live (for a little bit) with not knowing exactly how these neurons are working, but knowing that these diverse functions are clearly possible.

6 Comments:

  1. Great post. But don’t think neurogen is doing anything! Jokes aside, I think it is very important to recognize the behavioral double dissociation in hpc realms, esp neurogenesis
    Bravo!

  2. Excellent synopsis, thanks. I saw both posters, and it seems as if the interaction between stress, ventral hippocampal neurogenesis and affective/antidepressant behaviours is really becoming a fascinating research topic.
    One thing I’d note, though, is that “stress hormones have bad effects on behavior and neurogenesis in the context of social stress” might not be the best way to describe some of these results; these ‘bad effects’ could be evolutionarily conserved adaptive responses to stress, in that a little extra anxiety may not be a bad thing if your environment involves “getting beaten up by a big bully mouse and then having to constantly live next to him”. That doesn’t fully explain effects seen (in some studies) with the forced swim test, though, as increased behavioral despair (or ‘giving up more quickly’) doesn’t seem like a very adaptive behavior for the most part. Anyway, great post!

    • Hey Ian – thanks for bringing up that point. I completely agree that what we often call “bad” effects of stress may actually not be so bad but instead serve a very useful function. This paper by Oomen et al. is one example that always reminds me that stress, through “adaptive programming” can prepare the animal to better deal with stressful events in the future.

  3. Hello Professor Snyder,

    I was reading SfN 2011 blogs earlier today (I am unable to go, due to being a student finish his B.S. in Neuroscience), but I was lucky enough to come to this one later in the day.

    I’m trying to understand why you’re discussing stress and learning as you do. I think most neuroscientists and cognitive psychologists already know that stress interferes with learning and recall. But a neurobiological explanation is still in the works.

    Also, as I’ve been reading more about learning and conditioning, it makes sense that novel situations can break habits and cause new learning (enhanced stimuli awareness and intake) to occur in some species, such as humans/primates. I guess, then, it’s not really a stress hormone in that context, because it doesn’t stress the individual?

    Anyone, nice read. This is the kind of read I was hoping to get out of people blogging about SfN. Thanks.

    • Glad I could help you feel like you’re at the conference! I don’t have a clear answer to your questions – stress can certainly interfere with learning but it is also essential at the same time (perhaps depending on the amount of stress). Your novel situations idea is also interesting to me because there have been some great studies showing that in some seemingly unstressful situations (novel environment), animals actually are undergoing significant stress and if you remove that stress, the animals don’t remember what they learned….

  4. Pingback: Saving the best for the end: neurogenesis, plasticity and memory. #SFN11 | Functional Neurogenesis

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