The study was a bit of a fun learning experience for me for several reasons. As many of you know I recently changed labs and will be starting my own lab soon. So things are on the go and I haven’t had the time to dive deep into a study that is going to take several years to complete. But some research projects can be done quickly and still are able to produce very useful results. As I prepare for my own lab I was probably thinking, “What kind of projects could a Master’s student accomplish??”. And indeed we had a strong postbaccalaureate fellow in the lab for about a year who fit this description pretty well (she’s the middle author). Also, we had lots of tissue remaining from a recent study where we compared neurogenesis in mice and rats that could be used to answer other questions, thereby saving time, money and importantly, animals. So we decided to ask whether the maturation and survival of adult-born neurons differ between the aforementioned functionally-distinct hippocampal subregions.

The basic idea of the study.

BrdU was injected to birthdate+label new neurons and at various intervals kainate was given to “activate” all the neurons that had integrated into the circuitry, and formed synapses. This integration (a major step in the new neuron maturation process) can then be measured by immunohistochemically staining for gene products such as Arc that are expressed after synaptic activity. Our tissue was cut in the coronal plane, however, which is not ideal for isolating the septal and temporal ends of the hippocampus (though others have found that there are meaningful differences along this rostrocaudal axis). Since the rostral sections are purely septal (see blue portions, above) this subregion was not a problem. We then decided to basically “cut” the caudal sections in half and by analyzing only the ventral portion we were able to specifically target neurons located in the far temporal dentate gyrus (shown in red). We were also able to investigate whether new neurons are more likely to survive in one subregion than another, by counting the number of cells present before (at 7d old) and after (at 28d old) the period of cell death.

Since this article is completely open access you can see the actual data for yourself here. The short story is that new neurons matured faster in the septal dentate gyrus (all cells could express Arc by 3w of age whereas in the temporal dentate gyrus this didn’t occur until somewhere between 4-10w of age). The other new finding was that there were many more new neurons initially added to the infrapyramidal blade of the dentate gyrus but these neurons were much less likely to survive than neurons born in the suprapyramidal blade.

What is the significance of these findings? To me, they provide a framework for future studies. If you want to investigate new neurons specifically during their immature stage (when they might have unique functions) you certainly have to consider the anatomical location. But what if the main function for new neurons is not realized until they are fully mature? Well, if you plan to ablate or silence new neurons and examine behavioural effects, then you might want to wait longer if you’re planning on investigating emotion/stress-related behaviours that might rely more heavily on the temporal hippocampus. They also suggest that new neurons in the temporal dentate gyrus might have an extended unique role since they remain immature for longer. The peculiar survival difference between the infrapyramidal and suprapyramidal blades doesn’t do much to clarify the functions of these two regions, but it adds to the ever-growing list of differences that suggests they are truly distinct.

Often findings across labs do not match up as well as one would like so I am rather happy that Piatti et al. have found similar maturation differences in another species (mice) and using different methods (electrophysiological recordings from virally-labelled new neurons). So this is probably for real!

Lastly, a reviewer pointed out something very helpful, which is that it can be very difficult to discern the two blades of the dentate gyrus in caudal coronal sections (like this or those slightly more caudal where the dentate gyrus is essentially a blob). I spent a fair bit of time looking perplexed as I played with 3D paper models of the dentate gyrus but felt pretty cool doing so because similar strategies have been used by some of the foremost neuroanatomists of our time – see here. A 3D computer model that incorporated the blades of the dentate gyrus would have been very convenient (talking to you, Allen). In any case, we decided to remove our caudal blade analyses from the paper and instead only focussed on the septal infrapyramidal vs. suprapyramidal differences.

Reference: Snyder JS, Ferrante SF, Cameron HA (2012) Late Maturation of Adult-Born Neurons in the Temporal Dentate Gyrus. PLoS ONE 7(11): e48757. PMID: 23144957

¹in rodents

²in humans

There’s one week remaining before the  Society for Neuroscience annual meeting begins. That means you have about 6 days before you really really have to start tallying a list of presentations. Of course, WITH HUBBIAN*, you actually could put it off that long and still gather a great list of presentations. This is because Hubbian allows you to see related content, popular presentations, and presentations that are generating discussion. The key ingredient, which was missing until now, was the ability to save a list of presentations you’ve discovered on Hubbian.

DID I MENTION THE UNTIL NOW PART??

That’s right. Go nuts. Search and save.

I WANT YOU IN MY LAB!

The lab’s goal is to identify the role of adult neurogenesis in memory and stress-related behaviours. We inhibit neurogenesis with transgenic animals in order to understand how they contribute to these behaviours, viral tools for labelling and modifying neurons, immunohistochemistry to quantify and characterize the neurogenesis process, and in vitro electrophysiology to understand the circuit mechanisms by which these new neurons regulate behaviour. The neurobiology of behaviour extends far beyond adult neurogenesis, however, and so we are also generally interested in how neurons throughout the dentate gyrus, hippocampus, and related structures interact to guide behaviour.

I’m excited about the science but I’m also excited about doing it in the open. Discoveries exist well before they’re printed in a journal but in most cases people don’t appreciate this, since discoveries are rarely shared as they happen. I’d like to do things a little differently and get our science out in the open. Early. To assist others and stimulate discussion. I’d like to see undergrads in my lab have have their data available online in a citable format. You don’t need a peer-reviewed publication or a graduate degree to contribute something valuable to the scientific record (and perhaps your CV).

If this sounds like the bomb:

Potential postdocs can email me (jasonsnyder@psych.ubc.ca) directly to inquire about joining the lab. External funding deadlines are approaching and would go a looong way at this point.

Potential graduate students can contact me and apply through the Psychology or Neuroscience programs. Deadlines for a September 2013 start date are December 15 and January 30, respectively. There is also a June/July deadline for starting Neuroscience graduate studies in January 2014.

Potential undergraduates that are interested can email me directly. Previous lab experience is not a prerequisite to join the lab!

The lab will officially open in January 2013 and, after setting up, will be ready for real business around summertime. Oh, and I will be at the Society for Neuroscience meeting if interested folks would like to chat in person.

THIS IS EXCITING. READERS THAT ARE PREGNANT / HAVE HEART PROBLEMS STOP NOW CLICK HERE.

Over 30,000 people attend the annual Society for Neuroscience meeting and for this reason alone people either love it or hate it. On one hand, you can learn about any type of neuroscience research imaginable. On the other hand, it can be extremely difficult to find the meaningful stuff. The online itinerary planner. It works. Kind of. Did you search the right keywords? What about that new technique you’re interested in* – it’s mentioned in 100s of abstracts – which ones are worth checking out? What are other neuroscientists looking at? And in case you’ve missed something interesting you now find yourself at the meeting, aimlessly scanning titles, just a brainstem….being pulled towards the larger crowds…failing to penetrate the bobbling masses…

BUT THE KILLER APP THAT WILL SAVE YOUR LIFE HAS ARRIVED → Hubbian ←

SEARCH THE ABSTRACTS FOR WHATEVER TERMS YOU LIKE. ABSTRACT CONTENT, AUTHOR NAMES, EVEN PRESENTATION & POSTER BOARD NUMBERS.

SCROLL THROUGH THE SEARCH RESULTS, SELECT AN ABSTRACT AND, IF YOU LIKE IT, VOTE FOR IT! BETTER YET, LEAVE A COMMENT!

So you’ve scanned the abstracts a bit, maybe noticed the ‘related abstracts’ tool and stumbled across some presentations you’d never have found (awesome)…but now what?

HOW ABOUT GIVING YOUR BRAIN A REST. LET THE APP TELL YOU WHAT’S INTERESTING**

Do a search and sort the results by the number of views, votes or comments. Go back and sort by ‘best match’ to find content that is closest to your particular query. Sorting by time will tell you which presentations are coming up next. And you can always click the links at the very top of the page to see the most popular presentations of the entire meeting.

SHARE IT WITH OTHER NEUROSCIENTISTS THAT ARE NOT PREGNANT & DO NOT HAVE HEART PROBLEMS!

*Golgi staining

**or at least which abstracts are getting the most attention

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@Hubbian on Twitter

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Extra details for aficionados

• the development crew, which I was lucky enough to join
• database contains abstract content only
• got feedback? let us know!

• there is a blog!

• will be using Twitter hashtag #sfn12

• when you go to http://hubbian.com you’ll be automatically redirected to the mobile or desktop version. You can also visit the desktop version directly at http://hubbian.com/desktop.html – the mobile version is at http://hubbian.com/mobile.html

• Internet Explorer is not supported

Well, it could…and we did end our paper with the following:

Because the production of new granule neurons is itself strongly regulated by stress and glucocorticoids, this system forms a loop through which stress, by inhibiting adult neurogenesis, could lead to enhanced responsiveness to future stress. This type of programming could be adaptive, predisposing animals to behave in ways best suited to the severity of their particular environments. However, maladaptive progression of such a feed-forward loop could potentially lead to increased stress responsiveness and depressive behaviours that persist even in the absence of stressful events.

We had to end it somehow – I was just happy that after 3 years of work we were DONE²! But our final speculation makes it clear that, while this chapter may be done, the story is not. And this fact was rightly pointed out in a recent commentary by Lucassen et al. in Molecular Psychiatry³, where they continue the discussion and bring up some good points. Here is a loose elaboration on some of the outstanding issues they bring up.

Is a feed-forward cascade plausible? In other words, is it possible that stress reduces neurogenesis, which leads to a hyperactive HPA response, which further reduces neurogenesis, thereby additionally increasing the stress response etc etc, eventually damaging the brain and leading to depression? As Lucassen et al point out, stress typically reduces neurogenesis by only ~30% which is much smaller than the 100% reduction seen in our transgenic mice. Could a 30% reduction be enough to initiate this vicious cycle? What if it was chronic? People have looked in the past and not observed HPA alterations after smaller (but also equally large) reductions in neurogenesis, so the answer might appear to be negative. But there are many important differences between studies, including when stress hormones were measured (e.g. baseline or after stress) as well as factors such as life history, genetic makeup, and stressor controllability, as is suggested in the commentary. Of course, in reality, chronic stress has multiple effects throughout the hippocampus (and brain) and so the development of depression is certainly due to additive effects (this is both their sentiment and mine). And so perhaps in the real world a more modest reduction in neurogenesis does have the potential to tip the scales towards depression, if it is coupled with other (which?) pathologies.

How could so few adult-born neurons regulate the HPA axis? Depending on my mood, my thoughts on this question fluctuate quite a bit. Half of the time I think “This is ridiculous” and the other half of the time I look at the evidence and think “Heck yeah. Maybe⁴.” (see our recent review for more detailed arguments on the heck yeah side of things). In our study we reduced neurogenesis for up to 12 weeks, preventing about 50,000 cells from being added or 10% of the total population. More important than sheer numbers, however, is the ever-increasing evidence that adult-born neurons are different from mature neurons – more plastic, more excitable, uniquely neuromodulated. Some of the most intriguing evidence comes from one of the authors themselves who has shown that even 4 month old neurons (but potentially older?) undergo extensive structural modification following learning whereas perinatal-born cells do not. We have estimated that ~40% of the total granule cell population is added in adulthood in the rat and so my point is that in the real world we have to consider that there are probably cumulative effects of adult neurogenesis over years, and even decades in humans. And so the population of adult-born cells, and its functionality, may not be so small in the end.

Do new neurons sense detect stress through glucocorticoids? One common assumption is that glucocorticoid receptors are necessary for inhibition of the HPA axis…but must that always be the case? By 1-2 weeks of age the majority of adult-born neurons do express MRs and GRs and therefore certainly could directly detect glucocorticoid levels and initiate a shutting down of the HPA axis. But perhaps new neurons process stressful information that is relayed through glutamatergic pathways. In this scenario new neurons might not be required for sensing glucocorticoids and initiating negative feedback. Instead, after being stressed, they could be required for biasing the animal away from the negative experience (akin to perceiving a change in context, similar Opendak & Gould’s proposal for reconciling stress and memory hypotheses of new neuron function) which might reduce CNS drive on the HPA axis. This opens the door to the possibility that the HPA and behavioural roles of adult neurogenesis are somewhat dissociable, in which case a role for new neurons in the development of depression is not (only) through the feedforward cascade hypothesis but through direct effects on behaviour. This might also help explain the inconsistent links between stress hormones, hippocampal volume, and depression that plague the stress-depression literature.

So, we showed that adult-born neurons are required (in mice) for normal stress responses and emotional behaviour. Our final speculation was, well, just that – a leap towards the next big question. Maybe realistic, maybe not. Maybe a component of the real picture. In any case, the route has been mapped.

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References
Lucassen PJ, Fitzsimons CP, Korosi A, Joels M, Belzung C, & Abrous DN (2012). Stressing new neurons into depression? Molecular psychiatry PMID: 22547116

Snyder JS, Soumier A, Brewer M, Pickel J, & Cameron HA (2011). Adult hippocampal neurogenesis buffers stress responses and depressive behaviour. Nature, 476 (7361), 458-61 PMID: 21814201

Footnotes

¹You thought this footnote was going to be some comment on human depression vs. depressive-like behaviour in animal models but instead I just wanted to mention that, now that I’ve moved back to Canada, I feel compelled to use ‘behaviour’ instead of ‘behavior’ and it feels silly because the same people read this stuff no matter which country I’m in when I write it.

²Is there an emoticon for dusting the dirt off your hands, blowing smoke away from the tip of a revolver, or enjoying a refreshing beverage after chopping a bunch of wood or giving birth? Insert it here.

³One of the authors having actually commented on this blog (!), and who is 1st author on what looks to be a very interesting paper that is related to this whole discussion.

⁴I may be a pessimist. Realist? A guy with a healthy amount of skepticism?

⁵The photo? It’s a depression.

Now, on with the pictures! As always, I recommend high-res viewing (click on the image to view it, bigger, on Flickr).

Using a retrovirus, which infects dividing cells, I made the amazing discovery of four adult-born cells which all had the exact same shape and were located right next to each other!

More dentate granule cells, infected with Herpes Simplex Virus and expressing GFP.

In the process of learning the surgeries required to stereotactically inject the virus, you inevitably target the wrong regions. Which is fun because then you get a glimpse of something new. Here are GFP+ CA1 pyramidal neurons. You can see their axons projecting down and to the left, towards the subiculum.

More CA1 pyramidal neurons from the same animal but an adjacent section. I love the fanning of the dendrites. Click on the image and you can see spines in a higher resolution version.

Every day I see a retrovirally-labelled, non-neuronal (?) cell that looks more beautiful than the last one I imaged. Makes me want to cry.

Here are dentate granule cell axons, the mossy fibers, flowing through CA3 pyramidal neuron cell bodies, like a river gushing over rocks. In the woods. The balls on a string appearance is caused by the infamously large presynaptic boutons, which are distributed along the axon (like balls on a string, thin rope, or even dental floss).

]]> http://www.functionalneurogenesis.com/blog/2012/05/virus-a-new-tool-for-generating-pretty-pictures/feed/ 11 http://www.functionalneurogenesis.com/blog/2012/05/virus-a-new-tool-for-generating-pretty-pictures/?utm_source=rss&utm_medium=rss&utm_campaign=virus-a-new-tool-for-generating-pretty-pictures http://feedproxy.google.com/~r/FunctionalNeurogenesis/~3/lZcpzIXSnqw/ http://www.functionalneurogenesis.com/blog/2012/03/forming-and-recalling-memories-artificially/#comments Fri, 23 Mar 2012 13:29:54 +0000 Jason Snyder http://www.functionalneurogenesis.com/blog/?p=1444

Memory manipulation has become one of the most hotly pursued topics in neuroscience. After all, much or of who are is based on what we’ve learned, including memories that we can consciously recall as well as acquired desires and habits that can lead to problems like addiction. In rodents, we’ve known for decades that damage to the hippocampus can erase recently-formed memories. Studies of reconsolidation have shown us that when a memory is retrieved it becomes labile and allows for new information to be added, thereby creating an updated version. More recently we (humans) have been able to identify the neurons involved in memory formation and show that killing them, and only them, results in memory erasure. Bringing us even closer to the stuff of movies, studies by Garner et al. in Science and Liu et al. in Nature have now artificially controlled memory formation and recall. We’re essentially talking about reactivating memory by pushing a button. Yes – you can say “dude, whoah” now.

Artificially activating neurons

The two studies use contextual fear conditioning as their test of learning and memory. In this test mice freeze in a place where they previously received a footshock. In order to remember the context where they received a footshock certain genes are expressed in the neurons that encode the memory. Both groups hijacked one of these genes, c-fos, using it to drive expression of either a DREADD or channelrhodopsin, for pharmacological or optogenetic control of neural activity, respectively. The DREADD is a receptor for a molecule that doesn’t exist naturally in rodents, but when the molecule is injected into the mouse by a mad scientist it binds to the DREADD and causes neurons to fire action potentials kind of like would happen when a neuron is involved in forming or retrieving a memory. Channelrhodopsin also allows a neuron to be selectively activated but it is activated by light. In both studies, these tools served somewhat similar roles – when mice formed a memory the neurons that were involved in encoding that memory (neurons that express c-fos) became labelled in such a way that they could be selectively activated, artificially, by the mad scientist.

Creating a “synthetic” memory

In the Garner et al. study, when a mouse explored a new context (A) the DREADD was expressed presumably only in those neurons that were involved in forming a memory of context A. The next day they put the mice into a different context, B, and delivered footshocks while also activating those neurons previously involved in forming a memory for context A. This is where things get synthetic. Until now, scientists have played with relationships between memories by getting mice to naturally learn or recall two memories at once. But here Garner et al. are teaching the mice one thing naturally (that context B is scary) while simultaneously, artificially, reactivating a neural circuit that represents a previous memory (of context A).

They note that several outcomes could be predicted: 1) By activating context A neurons when the animals form a fearful memory, the mice could form an association such that they freeze whenever those context A neurons are activated in the future. However, this didn’t happen – they did several experiments to show that simply activating context A neurons, or even context B neurons, was not sufficient to evoke fear behavior. 2) Maybe the mice would learn to fear context B normally, since the sensory environment would be the same during both memory formation and retrieval. Again, no – mice were severely impaired at forming fear memories for context B, indicating that activity in context A neurons either interfered with memory formation or… 3) The artificial activation of context A neurons become a requisite component of the fearful memory for context B. Indeed, only when the mice were put back in context B (where they were shocked) AND those same context A neurons were activated (just as they were during training) the mice showed high levels of freezing.

Memory recall, push of a button style

The other study, by Liu et al., is a bit more straightforward to understand and the findings are a bit different. Instead of creating a hybrid memory by co-activating a previous memory (artificially) and a new memory (via experience) as in the Garner study, they used light-activation of channelrhodopsin-expressing neurons to reactivate a context fear memory. By doing this they could reliably cause the mice to freeze in a novel context, suggesting that they could artificially induce memory retrieval.

Differences in artificial memory recall

The Garner study is interesting proof that neuronal populations that are active during learning, even artificially, become essential for memory recall. The fact that only exposure to the shock context or only artificial activation of the context A neurons was insufficient to induce freezing suggests, to me, that these two components of the memory were somewhat distinct. The dogma that “neurons that fire together wire together” would lead one to expect that activation of only a subset of the memory trace would lead to more complete reactivation of the full memory. But perhaps the artificially activated neurons did not fire at the right frequencies or intensities to enable them to become completely integrated.

In contrast, with the optogenetic techniques employed by Liu et al., they were able to sufficiently activate neurons to induce memory recall. This was remarkable because, unlike the DREADD approach used by Garner where presumably all the relevant neurons in the brain could be targeted for reactivation, Liu et al. were probably only able to activate tens or hundreds of neurons due to limited expression of channelrhodopsin in the dentate gyrus of the hippocampus and limited ability of light to penetrate brain tissue and activate those neurons. It could be that CA3, which is downstream of the dentate gyrus, did its job and was able to reactivate the full memory trace from only partial inputs.

Clues about the dentate gyrus

There are a few other things about the Liu et al. study that are particularly noteworthy to me. The first is that they were able to induce recall of a specific experience by activating dentate gyrus neurons. In their control experiments they showed that freezing could only be induced when activating dentate gyrus neurons that were involved in encoding the fear memory but not neurons involved in encoding an unrelated memory. But some of the leading work in the field has shown that the dentate gyrus uses the same cells to encode many different types of experiences (via differences in firing rate). So, if it’s always the same population of active neurons in the dentate gyrus, how could they show this specificity? Wouldn’t activation of neurons for the unrelated memory be the same as activating neurons encoding the fear memory? Well, their c-fos-driven channelrhodopsin/YFP turned out to be a useful tool because it’s expressed in neurons for a long time after memory formation, unlike the endogenous c-fos whose expression decays to baseline levels after a couple of hours. They were then able to exploit these differential timecourses to show that two distinct experiences were in fact encoded by two distinct populations of neurons. This was not at all the take home message of the paper but, as an aside, provides some strong evidence that our knowledge about how information is processed by the dentate gyrus incomplete.

Optogenetic controls. Thank you.

The other aspect of the Liu et al. paper I really liked was the controls. Optogenetics is new, powerful and has already produced many major discoveries. But many are outside of my area of expertise and most have not yet been replicated and so I can’t help but be a little cautious of the validity of these findings. This was how I felt upon seeing similar findings presented at SfN way back in 2009 – cool, but really? The specificity of the induced recall (discussed above), the requisite lack of effect of light in the absence of channelrhodopsin, the fact that activating more neurons with bilateral light delivery enhanced recall, and the fact that activating fewer neurons (but neurons more closely linked to the fear memory) also enhanced artificial recall all bolster the claims and the validity of the method, for me. Cool stuff.

What’s next?

Can we implant a memory that doesn’t exist? Could a population of hippocampal neurons be identified, a priori, that represent a context to be learned in the future? And if you pair activity in those neurons with activity in the amygdala could you elicit fearful behaviour of a context even when nothing dangerous has ever happened there? The answer is probably yes. But it will still be pretty cool (for our grandchildren) to see it demonstrated.

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Postscript – be sure to check out coverage of the Liu study over at Nature’s Action Potential blog. Interesting because of the science but also because it gives a glimpse of the publication process – what did the reviewers think of the paper? How is it that the Garner and Liu studies were published in Science and Nature on the same day? Do Science and Nature….talk to each other?? They have the answer.

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Aleena R. Garner, David C. Rowland, Sang Youl Hwang, Karsten Baumgaertel, Bryan L. Roth, Cliff Kentros, & Mark Mayford (2012). Generation of a Synthetic Memory Trace Science, 1513-1516 : 10.1126/science.1214985

Xu Liu, Steve Ramirez, Petti T. Pang, Corey B. Puryear, Arvind Govindarajan, Karl Deisseroth, & Susumu Tonegawa (2012). Optogenetic stimulation of a hippocampal engram activates fear memory recall Nature : 10.1038/nature11028

The main concern by the authors is that citations for a given article are higher in Google Scholar than Scopus or Web of Science (well, one mainly focusses on the fact that they’re different). Higher because they include theses, patents, websites etc. Maybe also false positives.

I started thinking about this issue when I began applying for jobs. I didn’t have any fancy papers and so, for people outside of my field, noting the number of citations in my CV seemed like a decent way to make the point that some of these articles have had an impact. As I sent my applications I’d go back to Web of Science and check for the latest numbers and, this past year, I noticed that citations of some of my articles suddenly increased by up to 20%. Yay! But then I’d check the next day and they were low again (perhaps relating to changes in how citations were detected). So there was some glitch and I certainly didn’t want to appear to be inflating the numbers so I turned to Google Scholar. The numbers were higher, but consistent. For the most part the citations seemed completely legitimate as well.

So why were Google Scholar’s citation counts higher? Looking at my most cited paper, which has been cited 367 times (Google Scholar) or 267 times (Web of Science) or 287 times (Scopus) I found that Google Scholar included 11 Chinese articles, 10 book chapters, 15 theses, 4 patents, 1 blog (yours truly), 1 grant application, and 6 mysteries. Eliminating these 48 still leaves 319. Quite a bit higher than Web of Science and Scopus, probably because Google counts citations from articles that are still in press (my Neurobiology of Aging paper was published online but “in press” for 23 months, during which citations could be tracked in Scholar but not Web of Science). This is probably also why Google Scholar counts 17 citations (16 “normal”) of my most recent paper whereas Web of Science only counts 9 – many of these citing articles were recently published.

So should Chinese articles be excluded? Are book chapters irrelevant? Theses, well, no one reads theses so maybe there’s a bit of inflation there. I do think it’s a sign of impact when a blog, grant, or patent refers to your paper and believe that these things should be included in the citation counts (Google still isn’t great in this regard – I know of several blog posts on my papers that haven’t been detected by Google).

These are the reasons I specifically decided to use Google Scholar when adding citation counts to my CV. And so it’s funny to read about the “limitations of Google Scholar’s personalized citation reports” and how “I would not recommend using the reports for decisions that could affect careers”.

(for what it’s worth I did get a job, though clearly it’s all downhill from here)

There are lots of problems with the way scientific findings are communicated but this is perhaps the saddest one. The public pays for scientific research and then is charged again to read the results. People who do not have access to massive library holdings simply cannot access scholarly publications. Many scientists themselves cannot even access the papers they need because their institution cannot afford the subscriptions.

Fortunately, things are changing. For example, the National Institutes of Health requires that all federally-funded research be deposited into Pubmed Central where it is freely available to the public within 12 months of publication (this allows publishers to still make money off the article for a while, which is very kind of the US government). Another example is the new publishing model put forth by PLoS One and other journals, where the authors pay a fee that covers the costs of publication, archiving etc. Then the articles are made freely available to all because subscriptions are not needed to cover costs.

The way things are going, it is only a matter of time before scholarly publications and scientific information becomes freely communicated to those that paid for it. How long this transformation will take is the big question and there are two big movements in the US government that will play a big role. Two big movements that need your input.

First, there’s the The Research Works Act, a bill that, if turned into law, would prevent the open dissemination of scholarly articles. It would be a major step backwards. The Research Works Act would end Pubmed Central. It would dramatically slow down the pace and effectiveness of science. It’s put forth by members of congress who receive donations from publishers (e.g. Elsevier) that make massive profits off of taxpayer-funded scientific publications. Essentially, it wants to protect an outdated business model at the expense of education, scientific progress, human health, the environment, the economy, or anything else that benefits from the results of scientific research. See below for more information on the Research Works Act and, if you think it needs to be stopped, contact your representatives asap. If you’re not American you can still contact Representatives Issa and Maloney, who are sponsoring it. Many are also pushing scientists to contact their professional societies and university presses which are often in favor of preventing open access, for example through their membership with the American Association of Publishers (see here and here).

The second big thing, which must be related, is that the White House has put out a Request for Information, seeking input on how to promote open access to scholarly publications. Do you think it’s important for scientific information to be easily and freely available to all? If so, you now have a chance to offer feedback that could directly impact legislation on the topic. But you have to respond by Jan. 12. Apparently this Request for Information was extended an additional 10 days because the only input received was from for-profit publishers with no input coming from scientists themselves.

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Below is a list of links to the official US government sites for the Research Works Act and the open access RFI, people’s answers to the request for information, and sample letters to the representatives sponsoring the Research Works Act. Check them out:

The Research Works Act proposed by Representatives Issa and Maloney.

The White House Request for Information on public access to scientific publications (and update on the deadline extension plus link to related RFI on the management of digital data)

Kevin Zelnio’s passionate post urging scientists to get off their butts and do something about this. This is the first I read on the topic and what got me motivated to actually do something.

Michael Eisen’s post on Elsevier’s financial contributions to Rep. Maloney, who is putting forth the Research Works Act. His follow-up comment comparing publishers to obstetricians is great.

Heather Piwowar’s analysis of whether the Research Works Act protects jobs or is just fear mongering.

Cameron Neylon’s open letter to Representatives Issa and Maloney on the misguided idea that journals add value to articles which then needs to be protected as intellectual property, his note that the public pays for science not 2 but 3 or 4 no wait 5 times over, and his response to the RFI on public access to scientific publications.

Bjorn Brembs’ response to the RFI on public access to scientific publications.

John Dupuis’ very thorough list of links on the Research Works Act.

A thorough list of links and thoughts in Peter Suber’s Google+ post.

The third ventricle. Serious stuff.

An ultrasaturated look at the hippocampal fissure. Usually I’m not a fan of oversaturated neuro pix because strong signal is blown out and detail is lost. The converse, however, is that the faint signal become more visible and detail is gained. Need to work on some high dynamic range solution which would give the best of both worlds.

If GFAP was a catcher’s mitt then, uhh, cell nuclei would be…

Dorsal third ventricle. Seriousness continues. This thing could eat you.

Check out the highest resolution version of this and imagine falling in. You’re dead.

Not quite as impressive but illustrates something I’ve observed periodically in mice but never in rats: newborn neurons (in red) in the molecular layer.

An argument against the conventional red, green and blue color scheme of histological imagery.

An argument for the conventional red, green and blue color scheme of histological imagery. (Check out all the radial cell processes extending through the lower blade of the dentate gyrus. Red = thymidine kinase)

The blood vessel from the above image, bigger.

A transverse cut through two blood vessels (in contrast to the parallel cut, above). Where’s Waldo fans: find the catcher’s mitt cell in this picture.

More images on Flickr.