SFN2010 Itinerary Pt. 1

I have 62 items in my itinerary and I expect to add to it in the following weeks. There are always great presentations I find out about last minute and undoubtedly others that never see the light of (my) day. So fill me in if you have any tips. It’s not always the data that’s the most interesting part but often the presenter themselves, their ideas, methods, or the fact that you’ve known them since undergrad and you want to see baby pictures. My plan here is to share some of the potentially (you never know til you’re there) interesting presentations in my itinerary, bit by bit, over the next couple weeks.

1) 99.8/JJJ44 – The hippocampus is required for social recognition but not object recognition in Octodon degus
1Doshisha Univ., Kyotanabe City, Japan; 2RIKEN BSI, Lab. for Biolinguistics, Wako City, Japan

Huh? Octogon what? They’re rodents unlike any other rodent. They perform communal digging, nurse each other’s young, are born with their eyes open, and are intolerant of sugar and get diabetes. Even more interesting is the fact that they can switch their circadian rhythms between nocturnal or diurnal patterns and they’re apparently able to use tools (at least according to Wikipedia). So, basically I want to chat about Degus with these guys.

2) 100.19/KKK35 – Hippocampal granular neuron recruitment during the evocation of a recent or remote object recognition memory
1Neurobiologia Conductual y Cognitiva, Inst. de Neurobiologia, Univ. Nacional Autonoma de Mexico, Queretaro, Mexico; 2Neurobiologia Conductual y Cognitiva, Inst. de Neurobiologia UNAM, Queretaro, Mexico

Victor Ramirez-Amaya has done some interesting work on learning-related structural plasticity in the hippocampus and he’s also shown that the plasticity-related protein Arc is expressed in a delayed fashion after experience, probably as a part of the process of memory consolidation. Since there’s an emerging role for the dentate gyrus and neurogenesis in long-term memory I’m interested in this poster, which looks at activity-dependent Arc expression in the dentate gyrus and in young neurons after recent and remote(ish) memory retrieval.

3) 101.6/KKK46 – Spatial representation along the proximo- distal axis of CA1
1Kavli Inst. Sys Neurosci, Ctr. Biol of Memory, NTNU, Trondheim, Norway; 2Univ. Arizona, NSMA, Tuscon, AZ

The hippocampus is a convenient structure to study because its anatomical boundaries are distinct – the dentate gyrus doesn’t abut any other principal cell layers. CA3 and CA1 are easily distinguished from each other based on cell packing density. Probably for this reason there has emerged the assumption that these subregions are homogeneous in function. However, at least for the dentate gyrus it has become clear that it’s two blades are very different. And now, this abstract reports that the CA1 neurons that border region CA3 carry more spatial information than those at the other end, near the subiculum. I’m not entirely sure why I’m interested in this, but it may be because it suggests a certain level of care must be taken in future experiments (e.g. being consistent in where measurements are made) and it argues for better reporting in methods sections as to how measurements were made (because we now know that not all areas of CA1 are equivalent).

SFN2010 Neuroblogging List

So today the list of “official” SFN neurobloggers was released at the SFN website. And it immediately created a bit of an uproar. My initial beef was that I couldn’t ever seem to find the SFN blogging info without using Google. And also, I would like to know which other bloggers will be writing about SFN but I can’t seem to find this info.

For my part, Functional Neurogenesis is slated to post on the Theme A topic, development. But I will also post on more general topics in the neurobiology of behavior (mainly in animals – e.g. place cells, plasticity, structural or functional correlates of behavior). Posts are to be at least daily, following SFN’s guidelines. Which (if you know my frequency) means I will be taking full advantage of the big brown vats of lukewarm Starbuck’s coffee. No, seriously, I will probably take the streetcar to a cafe in old town to avoid the lines. And still make it to the poster session faster. Oh, also, there will be tweets.

This year’s SFN meeting marks the 1-year anniversary of the decision to startup Functional Neurogenesis. And it feels like things are only getting started – from within the scientific community FN has gotten some great feedback for which I’m thankful. The blogosphere is a whole different story. .

And now, because I haven’t made a list in weeks, and because there will be much coverage by non-official bloggers…

These bloggers will all be at the meeting. No guarantee that they’ll actually be blogging the meeting though. Let me know in the comments or email jasonscottsnyder (gmail) if you should be on here (or not).

Functional Neurogenesis / @jsnsndr
Genetic Expressions / @geneticexpns
Blogging on the Brain (@hillaryjoy
Fresh Eyes
House of Mind / @houseofmind
Pascal’s Pensees / @Pascallisch
Neuromusings / @neurodilettante
David Deriso / @davederiso
Dormivigilia / @Beastlyvaulter
Blogging Behavior / @aechase
Stanford Neuroblog / @stanfordneuro
SFN2010 / @thekhawaja

Fumbling Towards Tenure Track / @doc_becca
Some Lies / @Tideliar
Drugmonkey / @drugmonkeyblog
Neurocritic / @sarcastic_f
Bjorn Brembs / @brembs
Neurokuz / @kuzyx
Juniorprof / @juniorprofblog
Oscillatory Thoughts / @bradleyvoytek
Ferris Jabr / @ferrisjabr
Neuron Culture / David Dobbs
Danio Reri

Twitter lists of SFN attendees:
@stanfordneuro’s list
@mocost’s list
@noahWG’s list

Pattern separation: 370,000,000 papers 2050?

pubmed 2If you’ve been paying attention to the adult hippocampal neurogenesis literature at all, you noticed that “pattern separation” is gaining popularity as a research topic. A few quick searches on Pubmed confirm that a trend is indeed afoot.  For the years prior to 1999, only 15 Pubmed-indexed papers answer to the keyphrase “pattern separation.”  This number holds roughly steady through about 2003, and then it begins to take off.  As of this moment (September 24, 2010 @ 3:27pm CST), we are up to 81 papers. According to my back-of-the-envelope calculations, we are in a period of exponential growth.  Should this trend hold –and I see no signs of it abating– we can expect upwards of 370 million pattern separation papers by 2050. Can you imagine what a comprehensive exam will be like?  Your child (grandchild?) will face a stack of journal articles almost 500 miles high!  Al Gore, from atop his famous scissor lift, will inveigh against the massive deforestation wreaked by our prolific little research community.  What’s that you say? We’ll all be using iPads? Fair enough.
Continue reading Pattern separation: 370,000,000 papers 2050?

Someone finally dissects the role new neurons play in fear conditioning

Based on a true story – how progress is made in the field of adult neurogenesis*

  1. A group of scientists reduce neurogenesis and report a memory deficit.
  2. A second group repeats the experiment, with only a few minor differences in protocol, and fails to find a memory deficit.
  3. A third group, using the same species as the first group but a protocol more similar to the second group, replicates the original finding but only when the experiment is performed on Wednesdays.
  4. Faith is restored.
  5. Five groups report no such neurogenesis-dependent memory deficit.
  6. It is reported that developmental exposure to strontium reduces adult neurogenesis by 40% AND produces the much sought after memory deficit. In a technical tour de force follow-up experiment, artisanal cheeses restore neurogenesis and reverse the memory deficits. Causation is established.
  7. BDNF.
  8. Everyone proclaims the role of neurogenesis in memory and is totally confused at the same time.
  9. Someone systematically examines all of the variables in the memory test to determine whether or not the whole thing is a hoax and they should just change careers**.
  10. We have never gotten this far.

Even at level 8, the neurogenesis-fear conditioning story was one of the more convincing arguments of new neuron functionality. With this study by Drew et al. we may soon be jumping for joy as we appear to be graduating to level 9.

The contribution of adult neurogenesis to contextual fear conditioning was greatest when mice were only given a brief training experience – mice lacking adult neurogenesis showed reduced fear of a context where they previously received a single footshock during a brief (3 min) exploration session. With longer exposures to the context, or additional footshocks, neurogenesis-deficient mice showed normal memory. This finding could be explained by the fact that young neurons have a lower threshold for synaptic plasticity, allowing them to encode fleeting experiences that would be forgotten if left to mature neurons.

So, brief training protocols may now likely be my first choice, at least when using mice. In fact, the only times I have observed contextual fear memory deficits in mice has been after brief training protocols almost identical to those used by Drew et al. So we just might have taken a big step forward. If not, check back in 5 years for my revised “How progress is made” list.

*or any other field for that matter
**this is not entirely a joke because, in this case, it both 1) appears to not be a hoax, and 2) marks the launch of the next phase of Michael Drew’s career (congrats)

Drew MR, Denny CA, & Hen R (2010). Arrest of adult hippocampal neurogenesis in mice impairs single- but not multiple-trial contextual fear conditioning. Behavioral neuroscience, 124 (4), 446-54 PMID: 20695644

Do new neurons go through a critical period and then retire, never to be used again?

ResearchBlogging.org And here we have the latest, craziest hypothesis of granule cell function. Crazy not because the authors have lost their minds but because the story of the dentate gyrus, where adult neurogenesis occurs, is becoming more peculiar every day. The underlying premise of this paper by Alme et al. (which we will examine later) is that granule neurons go through a critical period during their development when they are more likely to contribute to memory encoding. Here it’s hypothesized that, once the critical period is over, they shut down. Forever. Hundreds of thousands of neurons never to be used again. It’s not every day you get to read such bold and novel ideas. Their hypothesis has similarities with that proposed by Aimone 2006, that adult neurogenesis causes different cohorts of neurons to be immature at different phases of an animal’s life, thereby separating memories according to time. The question here is whether these neurons can be reactivated once their critical period is over. Continue reading Do new neurons go through a critical period and then retire, never to be used again?

Olfactory bulb neurogenesis big bigger biggest

And now for a journey outside (rostral, to be precise) of my comfort zone. These three pictures show new neurons in the mouse olfactory bulb at successively greater magnifications. Probably inspired by the science magazine I read as a kid that would show high mag photos of everyday objects (with corresponding low mag photos as the answers).

With a 10x objective I could capture nearly the entire bulb (saggital section) in a single field. You can see newborn BrdU+ cells (green) scattered throughout, most co-labeled with doublecortin (red). In the bottom left area you can see about a dozen glomeruli – groups of neurons that represent different odors, located just one synapse upstream of the nasal epithelium. Whereas the majority of adult-born olfactory neurons are inhibitory interneurons, a smaller number of new neurons surrounding the glomeruli (periglomerular neurons) are dopaminergic. (click on the images for full sized versions – 2048 x 2048 pixels)

low magnification doublecortin and BrdU

Continue reading Olfactory bulb neurogenesis big bigger biggest

Old news gets the shaft

I was recently reading a number of old papers on memory and synaptic tagging and found myself wondering whether they were bloggable. My instincts said yes but the more I thought about it the more I realized they’re several years old and that is ancient by the standards of Twitter and the blogosphere*. I enjoyed reading them but would my readers enjoy them? Is it useful to report on “old” science? If it is then why is it so rare? Continue reading Old news gets the shaft

Low mag visualization of calbindin & zinc transporter expression in mouse brain

confocal image calbindin and zinc transporter expression in mouse brain

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.

What IS the dentate gyrus doing to CA3?

Calbindin expression in the dentate gyrus/hippocampus is variable, and particularly weak in young neurons

A fundamental property of the hippocampus is its ability to rapidly encode memories while simultaneously keeping them distinct. Recording from hippocampal neurons one can clearly see that different populations of neurons are active as a rat explores two environments. This is thought to be one mechanism by which information is kept distinct in the brain.

For the last 15-20 years it has been thought that the dentate gyrus (DG), a major subfield of the hippocampus, serves to take small changes in incoming sensory information and orthogonalize them (i.e. make them more different). This idea was built in part on the fact that there are many more DG neurons than upstream cortical neurons. Thus, the DG could use completely different populations of neurons to represent different sets of incoming information and then pass on these representations to CA3, which may bind them into coherent events/memories (the interconnectedness of CA3 neurons, via “recurrent collatorals”, is thought to be a mechanism by which the different components of a memory are bound together).

However, a “problem” arose when Leutgeb et al. found that it is always the same population of dentate granule neurons (~1% of the total population) that are active as an animal explores different environments, even very different ones. This was a bit of a surprise. Still consistent with the proposed role of the DG in orthogonalizing information, however, was the fact that the DG neurons fired (i.e. generated action potentials, which transmit information from neuron to neuron) at different rates/frequencies in the different environments. Thus, changes in sensory information were represented by changes in patterns of activity within the same population of cells, not by recruiting different populations of cells. This is but one study – the question of how the DG encodes and extracts information is far from settled (e.g. what are the other 99% of granule neurons doing? Surely there is a situation in which they are active, no?). But the findings were robust and raise many questions, namely: How does the same population of DG neurons activate different populations of downstream CA3 neurons, during different experiences? Continue reading What IS the dentate gyrus doing to CA3?

Spatial learning sculpts the dendritic arbor of adult-born hippocampal neurons

young neuron dendritesDendrites 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.
Continue reading Spatial learning sculpts the dendritic arbor of adult-born hippocampal neurons

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