Action Potential

The next installment of the Nature Network Neuroscience group journal club is now live. The paper discusses a potential therapeutic strategy involving the upregulation of the dopamine receptor D2R that may be beneficial in the treatment of cocaine abuse and addiction.

The contributor discussing this paper for the neuroscience group is Áine Duffy, a postdoctoral fellow at Weill-Cornell Medical College in New York. I want to thank Áine for her participation.

Posted by Noah Gray at 02:28 PMon April 30, 2008 | Permalink | Comments (2) | TrackBacks (0)
Categories: Noah Gray, Interesting Neuroscience, Journal Clubs

Our May editorial takes a brief look back at some of the history of Nature Neuroscience. We also present some of the most-cited papers over the past decade. This is an interesting exercise, as it provides an opportunity to reflect on the interests of both the authors and readers over the past decade.

As promised in the editorial, here is a list of most highly cited paper from each year of the journals publication, up until 2005 (going beyond that, things get a little unreliable since the citation half-life is usually quoted as being somewhere between 2-3 years):

1998: Nature Neuroscience 1, 69 - 73 (1998) ; doi:10.1038/271
Cortisol levels during human aging predict hippocampal atrophy and memory deficits
Sonia J. Lupien, Mony de Leon, Susan de Santi, Antonio Convit, Chaim Tarshish, N. P. V. Nair, Mira Thakur, Bruce S. McEwen, Richard L. Hauger & Michael J. Meaney
447 citations

1999: Nature Neuroscience 2, 266 - 270 (1999) ; doi:10.1038/6368
Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus
Henriette van Praag, Gerd Kempermann & Fred H. Gage
839 citations

2000: Nature Neuroscience 3, 1301 - 1306 (2000) ; doi:10.1038/81834
Chronic systemic pesticide exposure reproduces features of Parkinson's disease
Ranjita Betarbet, Todd B. Sherer, Gillian MacKenzie, Monica Garcia-Osuna, Alexander V. Panov & J. Timothy Greenamyre
876 citations

2001: Nature Neuroscience 4, 95 - 102 (2001) ; doi:10.1038/82959
Abstract reward and punishment representations in the human orbitofrontal cortex
J. O'Doherty, M. L. Kringelbach, E. T. Rolls, J. Hornak & C. Andrews
454 citations

2002: Nature Neuroscience 5, 452 - 457 (2002) ; doi:10.1038/nn842
Immunization reverses memory deficits without reducing brain A burden in Alzheimer's disease model
Jean-Cosme Dodart, Kelly R. Bales, Kimberley S. Gannon, Stephen J. Greene, Ronald B. DeMattos, Chantal Mathis, Cynthia A. DeLong, Su Wu, Xin Wu, David M. Holtzman & Steven M. Paul
317 citations

2003: Nature Neuroscience 6, 43 - 50 (2002) ; doi:10.1038/nn980
Neuron-to-astrocyte signaling is central to the dynamic control of brain microcirculation
Micaela Zonta, María Cecilia Angulo, Sara Gobbo, Bernhard Rosengarten, Konstantin-A. Hossmann, Tullio Pozzan & Giorgio Carmignoto
292 citations

2004: Nature Neuroscience 7, 847 - 854 (2004) ; doi:10.1038/nn1276
Epigenetic programming by maternal behavior
Ian C G Weaver, Nadia Cervoni, Frances A Champagne, Ana C D'Alessio, Shakti Sharma, Jonathan R Seckl, Sergiy Dymov, Moshe Szyf & Michael J Meaney
413 citations

2005: Nature Neuroscience 8, 828 - 834 (2005) ; doi:10.1038/nn1463
5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression
Lukas Pezawas, Andreas Meyer-Lindenberg, Emily M Drabant, Beth A Verchinski, Karen E Munoz, Bhaskar S Kolachana, Michael F Egan, Venkata S Mattay, Ahmad R Hariri & Daniel R Weinberger
236 citations

And, the Top 10 overall:

1. 876 citations
Nature Neuroscience 3, 1301 - 1306 (2000) ; doi:10.1038/81834
Chronic systemic pesticide exposure reproduces features of Parkinson's disease
Ranjita Betarbet, Todd B. Sherer, Gillian MacKenzie, Monica Garcia-Osuna, Alexander V. Panov & J. Timothy Greenamyre

2. 839 citations
Nature Neuroscience 2, 266 - 270 (1999) ; doi:10.1038/6368
Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus
Henriette van Praag, Gerd Kempermann & Fred H. Gage

3. 746 citations
Nature Neuroscience 2, 260 - 265 (1999) ; doi:10.1038/6365
Learning enhances adult neurogenesis in the hippocampal formation
Elizabeth Gould, Anna Beylin, Patima Tanapat, Alison Reeves & Tracey J. Shors

4. 595 citations
Nature Neuroscience 2, 861 - 863 (1999) ; doi:10.1038/13158
Brain development during childhood and adolescence: a longitudinal MRI study
Jay N. Giedd, Jonathan Blumenthal, Neal O. Jeffries, F. X. Castellanos, Hong Liu, Alex Zijdenbos, Tomá Paus, Alan C. Evans & Judith L. Rapoport

5. 509 citations
Nature Neuroscience 3, 661 - 669 (2000) ; doi:10.1038/76615
Proteomic analysis of NMDA receptor−adhesion protein signaling complexes
Holger Husi, Malcolm A. Ward, Jyoti S. Choudhary, Walter P. Blackstock & Seth G. N. Grant

6. 476 citations
Nature Neuroscience 3, 292 - 297 (2000) ; doi:10.1038/73009
Voluntary orienting is dissociated from target detection in human posterior parietal cortex
Maurizio Corbetta, J. Michelle Kincade, John M. Ollinger, Marc P. McAvoy & Gordon L. Shulman

7. 454 citations
Nature Neuroscience 4, 95 - 102 (2001) ; doi:10.1038/82959
Abstract reward and punishment representations in the human orbitofrontal cortex
J. O'Doherty, M. L. Kringelbach, 2, E. T. Rolls, J. Hornak & C. Andrews

8. 447 citations
Nature Neuroscience 1, 69 - 73 (1998) ; doi:10.1038/271
Cortisol levels during human aging predict hippocampal atrophy and memory deficits
Sonia J. Lupien, Mony de Leon, Susan de Santi, Antonio Convit, Chaim Tarshish, N. P. V. Nair, Mira Thakur, Bruce S. McEwen, Richard L. Hauger & Michael J. Meaney

9. 435 citations
Nature Neuroscience 3, 284 - 291 (2000) ; doi:10.1038/72999
The neural mechanisms of top-down attentional control
J. B. Hopfinger, M. H. Buonocore & G. R. Mangun

10. 413 citations
Nature Neuroscience 7, 847 - 854 (2004) ; doi:10.1038/nn1276
Epigenetic programming by maternal behavior
Ian C G Weaver, Nadia Cervoni, Frances A Champagne, Ana C D'Alessio, Shakti Sharma, Jonathan R Seckl, Sergiy Dymov, Moshe Szyf & Michael J Meaney

An interesting list that spans quite a few sub-disciplines, hopefully reflecting our attempt at balance when covering all fields for our broad readership. What interesting trends do you see? Any interesting developments that you find surprising or completely expected? I look forward to reading your analysis.

Posted by Noah Gray at 01:20 PMon April 25, 2008 | Permalink | Comments (5) | TrackBacks (0)
Categories: Noah Gray, What's New in NN?

The next installment of the Nature Network Neuroscience group journal club is now live. The paper provides evidence that in unanesthetized animals, sounds are sparsely represented in the auditory cortex.

The contributor discussing this paper for the neuroscience group is Lizzie Buchen, a science writer for Discover Magazine in New York. I want to thank Lizzie for her participation.

Posted by Noah Gray at 10:36 AMon April 17, 2008 | Permalink | Comments (0) | TrackBacks (0)
Categories: Noah Gray, Interesting Neuroscience, Journal Clubs

I recently attended the Alzheimer's Disease Keystone meeting in Keystone, CO and became more acutely aware of something than ever before: academia and drug companies really like one another. Sure, the latter always loved the former, since collaborating with university-based scientists often made the publications arising from the private sector look a little more legit. On the contrary, the reciprocity in this relationship has not always been there. There is without a doubt some sub-disciplinary differences in this complex relationship, but in the basic science departments that I lurked around, if you were associated with a company (or worse, left academia for a position there, succumbing to the power of the Dark Side), there was always talk of whether or not you could be trusted. Because companies need publications to prove the legitimacy of their product, right? And the legitimacy determines how much money everyone makes, right? So with such conflicts of interest, could the scientist, or the data being produced by these people, be trusted?

That about sums up the position I feel a lot of academics have taken in the past. But before some commenter blows a gasket defending the ethics of research in the private sector, please understand that I am not trying to question the moral fabric of anyone holding a pipetteman in one hand and stock options in the other. I am simply reporting what my impression was from my peers in university department(s) and from other "non-profit" scientists with whom I associated. Obviously, the stereotype I am describing is flawed, but it is (was?) still one of those non-PC opinions (sometimes not so) secretly held by many an academic. But after what I observed at this AD meeting, I think that I can officially say that the hatchet has been buried and apparently, if you don't have a slide in your talk disclosing your potential private sector conflicts, then your lab is either financially-challenged, or you are a taxonomist. Why the big change? That's easy --- money. With the ever-widening gap between the number of NIH proposal submissions and the funding line, academic labs, now more than ever, need to find additional sources of money. It's funny how being broke will make a person change his/her mind about something...

Philanthropic entities, like the Simons Foundation, McKnight Foundation, and the Pew Charitable Trusts, have in the past, and are currently supporting, academic neuroscience research in a variety of ways. However, this source of funding is still not large enough to significantly shrink the gap. Enter Big Pharma, and little biotech, for that matter. The relationship between company and academic lab can take a variety of forms; from collaborative reagent testing/sharing, to complete underwriting of whole parts of the academic lab's program. At the meeting, I talked to PIs, post-docs and students regarding this relationship and everyone seemed to be extremely comfortable and happy with the arrangement. The companies, to their credit, see an obvious need, and are enthusiastically filling it. How enthusiastically? In one instance, a company that was collaborating with an academic lab flew a representative to this AD meeting, if only to hang up a poster for the researcher and remove it after the session was over. These previously-uneasy bedfellows are really not so much anymore. Certainly, there are fields that do not have strong ties to industry, but based on my conversations and observations, those unfortunate researchers tragically working in such areas are not avoiding contact out of elitist machismo, or fear of some "unholy" moral corruption, but rather, because they just haven't found a good "hook" to convince a company their lab's work could reap products or information that could eventually improve the company's bottom line.

I don't really see too many people raising an eyebrow anymore when they are told about a certain academic leaving for industry. The stigma is just not there, like it was when I was a graduate student (when I sat as the student representative on my graduate school admissions board, there was often talk of accepting only students who we could predict were more likely to do something "productive" with their future, and not throw away their education by going into the private sector). In addition, companies, more than ever, are encouraging their scientist employees to work on projects that are not necessarily related to specific product development goals, but rather have basic inquiry as the motivating factor (like at Genentech). In my opinion, by loosening the scope of the research they choose to fund, companies place themselves in a better position to attract elite scientists. These strong thinkers bring obvious intellectual capital to the table, assisting with the company's product development, and are simultaneously kept happy because of the intellectual freedom to pursue other projects. This can only enrich and grow the entire creative research process within the company. So, for the moment, the strong marriage between academia and industry seems to be good for science as a whole. But how long will the honeymoon last?

Posted by Noah Gray at 05:22 PMon April 14, 2008 | Permalink | Comments (2) | TrackBacks (0)
Categories: Noah Gray, Science Policy, Random Thoughts

The next installment of the Nature Network Neuroscience group journal club is now live. The paper discusses the role for brief adaptation in the improvement of population-based encoding accuracy during sensory information processing.

The contributor discussing this paper for the neuroscience group is Adam Packer, a graduate student at Columbia University in the lab of Rafa Yuste. I want to thank Adam for his participation.

Posted by Noah Gray at 02:41 PMon April 08, 2008 | Permalink | Comments (0) | TrackBacks (0)
Categories: Noah Gray, Interesting Neuroscience, Journal Clubs

I would say no. Grant proposals are a precious commodity, especially in this day and age of reduced funding and evaporating money. However, in a recent Nature correspondence, Dr. Noam Harel describes his vision for a centralized grant repository, ideally open to the public, where researchers could place their best ideas, allowing various funding agencies to discover the plans most-suited to their respective agendas. Dr. Harel likens this potential web manifestation to something like eBay, Facebook or Google, but for scientists and funding agencies. A more apt analogy might be Monster.com, with both sides searching for their ideal match, and a long-term relationship (perhaps I am now making it sound more like eHarmony.com...).

When it comes to the integration of scientific communication and technology, I am extremely optimistic, and although I don't reject Dr. Harel's idea entirely, I just don't see it taking off in its presently-proposed form.

Grant writing is one of the most time-consuming and challenging parts of an academic scientist's life. S/he knows what needs to be done and how to produce a cool result, but translating these actions into words that the evil, intimidating and blood-thirsty study section will find appealing takes patience and care, taking much precious time away from bench work. This leads to my #1 reason why this sort of repository would not work: there is simply too much competition out there to risk losing essential intellectual capital.

Sure, I bemoaned the lack of unpublished data being presented at meetings in this blog before, but I draw a distinction here. Presenting unpublished data ready for public consumption is still a vastly safer endeavor than publicly revealing one's approaches for tackling an interesting problem or creating new research tools. In addition, there are countless stories in science describing how one particular experimental strategy looked odd or downright foolish, at least until it produced a fantastic result. It is always exciting to reveal one's seemingly foolish strategy once it has been successful, but until then, most people would rather pursue their hair-brained ideas by themselves. Come on, how many of you out there didn't have a "secret project" that you never told your PI about, at least not until after it worked? Sometimes, we don't want public criticism when we are in brainstorming mode, begrudgingly granting an exception to our study section colleagues.

Guarding potentially wacky experimental escapades is similar to the secretive nature that soon-to-be parents adopt regarding their selected baby names. They are not going to tell you the names until after the birth of the child because, frankly, they don't want your feedback. After the birth certificate has already been filed, you, being the politically-correct individual that you are, will oblige them by complementing on their selection, since it is obviously too late to change anything. I feel the same concept applies to research that yields positive results. I am not suggesting that scientists shouldn't or don't discuss their potential experiments with others, but bouncing ideas off of trusted lab mates and posting them in a public repository are very different beasts. I simply feel that scientists are far from reaching the comfort level required to lay bare their most intimate experimental designs to the general public without first fully testing them to see if they work.

Hindsight is always 20/20. Most of the time, reviewer comments, whether on a publication or an RO1 proposal, are fairly constructive and can improve a paper or grant. After receiving feedback from a small group of peers (the study-section included), the grant writer will likely adopt certain suggestions, and modify other portions of the grant. This makes the proposal a better document and more likely to be funded by the agency represented by the original reviewers, or perhaps by another funding organization, if the author decides to try his/her luck elsewhere. Since any astute reviewer would likely detect the same major flaws, it would serve the author well NOT to leave the grant in a repository, but to instead modify and revise it for the next assessment. What advantage is it to the researcher, or to another funding agency, to have a sub-par grant evaluated again, using up precious time and reviewing resources? Of course, the public repository could be made so that new versions of the grant could be uploaded, appending the older version, but in the interim as the author is revising the grant (which can take months), the weaker version would be sitting there possibly turning off potential agencies (who may not bother to even look at a revision if they found the original version unsuitable) or causing confusion if the authors decide to move in a different scientific direction, with the revised proposal scarcely resembling its parent.

Currently, this grant repository does not exist, but could pre-print servers, like Nature Precedings, act in its place? After all, although they are currently not posting user-submitted research proposals, Precedings has listed some open science proposals. There may even be some interest in this submission category, as indicated by a recent blog post. Do I think that this is a good use of Nature Precedings? The answer is no. A preprint server and grant repository are separate entities and should remain as such. Mixing proposals and non-peer-reviewed research would not benefit the community and could potentially cause confusion regarding the mission of the preprint server. I think that the editors of Precedings are following the right course by limiting the submissions to data and completed experiments. Which means that the preliminary data in grants would be perfectly appropriate to submit, but let's leave out the "Aims" sections.

I mentioned at the beginning of this post that I didn't entirely reject Dr. Harel's idea. The mixing and matching of proposals and agencies, akin to my Monster.com reference, is not a bad one and could work. It is often hard for scientists to keep up with all of the new private foundations and charitable entities willing to provide millions of dollars to push progress in their favorite research area. But perhaps I could limit the scope of Dr. Harel's proposal and suggest that any centralized repository would provide a simple one-page form allowing a laboratory to briefly detail their interests and loosely describe their plans, providing just enough information for the funding agency to "invite" the full proposal, if appropriate, while protecting the ideas of the scientist from general public exposure. These characteristics could potentially promote increased participation by those writing the proposals. With application requests and applications in the same place, it would only be a matter of time before the two found one another. This "limited scope" model of the repository would also still provide a means to preserve Dr. Harel's other good ideas of encouraging joint-funding (if two agencies are both interested in the same project), or inspiring collaborative projects between labs seeking to examine the same questions.

I guess I'll get to work pitching my twist on this idea to the people controlling the money dedicated to special projects here at NPG and see if we can get "Nature Grant Matchmaker" off the ground...

Posted by Noah Gray at 05:34 PMon April 01, 2008 | Permalink | Comments (1) | TrackBacks (0)
Categories: Noah Gray, Science Policy, Random Thoughts