Author Archives: I-han Chou

About I-han Chou

Neuroscience editor for Nature

Reviewing gender

Posted on by
4
Original image courtesy of Stuart Miles / FreeDigitalPhotos.net

We’re back! Apologies for the long radio silence – day job, what can I say.

Last week Nature published a leader reflecting upon our performance as editors and journalists in the gender balance of our referees, commissioned authors, and journalistic profiles. The verdict?  Plenty of room for improvement – in 2011, only 14% of Nature’s 5,514 manuscript referees were women.  Those numbers are for all areas, both physical and life sciences. I don’t have the exact number for just neuroscientists but a quick partial analysis suggests it is in the same ballpark. How good/bad is 14%? According to a 2007 survey of North American neuroscience programs, 36% of neuroscience assistant professors, 28% of associate, and 21% of full professors are women. I don’t know what those percentages would be if you included neuroscientists from the rest of the the world (I’m guessing they would be lower), but I am fairly confident in saying we haven’t been grossly overrepresenting women in our referee picks.

So how do we choose our referees?  Continue reading →

Too much of a good thing?

Posted on by
1

From Wilson et al.

We published another double header yesterday, this time on the role of particular cell types in visual responses. Both studies describe the effect of optogenetically manipulating various interneuron classes in mouse visual cortex. The papers are Lee et al. from Yang Dan‘s lab and Wilson et al. from Mriganka Sur‘s labs. And in fact, both were preceded by Atallah et al. from Massimo Scanziani’s lab, which appeared in Neuron earlier this year. Which means a bonanza of data on the effects of activating parvalbumin-expressing interneurons, and also a bonanza of different conclusions about their exact role – everyone comes to slightly different conclusions.

We’ve discussed joint (and triple) publication a number of times already on this blog, including situations where findings diverge. We even just recently discussed a triple publication involving a paper from Yang Dan’s lab. So I’ll leave it to you to extrapolate the editorial discussions that likely took place in this case, but if anyone wants to know more, leave a comment. Instead, I’ll touch on another question that we get asked fairly regularly: what do we do when authors submit papers to us in quick succession? Is there a limit on how many papers from one lab we will publish per year? Since we’re mentioning today a paper by an author who had a paper covered in the previous blog post, you can infer that number is at least two. Just kidding. Of course we have no limit. Scientific progress unfolds at different rates, and sometimes labs have some very good years. As long as a study has potential impact, we are happy to consider. Continue reading →

A tale of three papers

Posted on by
Reply

From Figure 1, Li et al.

I wanted the title of this post to be “A tale of two one two three papers” but I couldn’t figure out how to get strikethroughs in the title field. And I thought “A tale of two, make that one, no make that two again, oops now three” might be a bit cumbersome. As promised, here’s another installment of the discussion of what happens when we receive conceptually related/overlapping papers. It starts with a paper that appeared just yesterday in Neuron by Kenichi Ohki and colleagues describing how mouse visual cortex neurons that developed from the same neural progenitor cell tend to be more similar functionally than those that did not.

Why is this significant? First a little background. Cells in visual cortex are tuned to different aspects of visual stimuli, such as orientation or direction, and anatomically are organized quite specifically. Cells with similar preferences tend to cluster together and to be selectively connected with each other (though to differing degrees in different species), and this specificity may underlie some of the many computations required to turn photons of light hitting our eyes into comprehensible percepts.  It’s been proposed that this clustering could start in early development; neurons born from the same neural progenitor migrate vertically to form columns of sibling neurons, and could be the basis for clusters of adult cells with similar properties. That link hasn’t been demonstrated experimentally until now, and Ohtsuki et al. provides some evidence in support of it.

Now, visual cortex aficionados among you may think this sounds a bit similar to Li et al., a paper by Yang Dan and colleagues that appeared a few months ago, and indeed it is. And you may also recall that THAT paper appeared alongside Yu et al. from Songhai Shi’s lab about the development of synapses between sibling neurons.

So here’s the story from the beginning (or rather, the beginning of our involvement with the manuscripts).

Continue reading →

Autism, synapses and mice – pairs division

Posted on by
2

From Won et al.

Again, we’re behind on blogging – you guys are keeping us busy with great neuroscience – but here is the story of a pair of papers that appeared back to back in last week’s issue and a continuation of the discussion started here by Noah about the process of joint publication. The two papers by Tobias Boeckers and colleagues and by Eunjoon Kim and colleagues were independently submitted and both describe autism-like phenotypes of mice with mutations in the gene Shank2. In human studies, SHANK2 has been associated with rare cases of autism and these two mice add to the ever-growing list of rodents (according to SFARI.org, 17 rodent models debuted in 2011 alone) that are being created to investigate the functional consequences of genetic mutations linked to autism, in the hopes of understanding mechanisms underlying core symptoms. Shank2 is a scaffolding protein that regulates excitatory synapse function by holding together various molecules such as neurotransmitter receptors and signaling proteins. Mutations in another member of the same gene family, SHANK3, are also associated with human autism, and mutant mice display behaviors reminiscent of ASD symptoms, such as social deficits and obsessive behavior. So this protein family, and more generally, glutamatergic transmission, is potentially one promising line of investigation. Continue reading →

Call and response

Posted on by
Reply

From Ramsden et al. addendum

The (highly abbreviated) life story of a paper appearing in Nature often goes something like this: ideas are birthed and experiments envisioned. Pilot experiments are run, yielding beautiful preliminary data. Replication and controls are then gathered over the course of months, if not years of hard labor. The paper is written, submitted, and reviewed. A few (two is typical) rounds of review and revision later, it is published (with highly variable degrees of reviewer and editorial unanimity). But this is by no means the end, rather, just a milestone in the evaluation process by the community.  In journals, post-publication evaluation has traditionally occurred in the form of peer-reviewed follow-up papers or formal commentary. This may change someday as alternative forms of scientific publishing are explored, but for today we’ll talk about a formal addendum we’re publishing on a 2011 paper by Cathy Price and colleagues and invite you to add to the discussion.

Continue reading →

Motor recovery within grasp

Posted on by
Reply

I’m on the road (attending a symposium at MIT: New Insights on Early Life Stress and Mental Health) so this one’s going to be brief. Neural prosthetics are an exciting interface between basic research and technology, an area where the path from fundamental discoveries in the organization and function of the brain to translational advances has been remarkably clear. Cochlear implants have already demonstrated their utility for replacing/enhancing auditory function, and more and more promising advances are coming out all the time in retinal implants. Motor prostheses are another exciting area with the promise to restore motor control to paralyzed individuals and today’s paper  by Lee Miller  and colleagues represents another step towards a potential prosthetic for spinal injury patients. Continue reading →

Parietal decision sequences – and more of mice and monkeys

Posted on by
Reply

From Figure 2 of Harvey et al

Back in the 1990’s, one of the most intense battlegrounds in systems neuroscience was in monkey posterior parietal cortex. Labs competed to claim what a little strip of cortex called lateral intraparietal area (LIP) really does – decision, movement planning, attention, reward, or all of the above – mostly using single cell recording in behaving monkey. The experiments were (and still are) tough: standard operating procedure requires a well-trained monkey who will perform hundreds if not thousands of trials a day and then isolating neurons one at a time to find ones that respond during some interesting part of the trial. And then lots and lots of repetition so that you can average over many neurons. All things considered, it’s remarkable how much the field has been able to learn with this toolbox.

Fast forward to present day, there’s a new kid on the block. As I discussed a few weeks ago, rodent behavior and physiology is booming. People are taking on questions previously studied mainly in primates and are taking full advantage of the recent storm of new techniques. This is typified by today’s paper by Chris Harvey, Philip Coen, and David Tank, which goes back to the question – what does posterior parietal cortex do during a decision task?  They imaged populations of neurons while mice used visual cues to navigate a virtual maze. Just like in primates, individual neurons were selective for different choices that the mouse made. But unlike in primate parietal cortex, where neurons tend to have sustained responses leading up to the time of decision, individual neurons responded transiently in different portions of the trial. So as a population, different choices were represented by distinct sequences of neuronal activity. This kind of sequential firing has been seen in other parts of the rodent brain such as hippocampus, but not in posterior parietal cortex.  Continue reading →

Layer magic and monkey business

Posted on by
1

Layers of human cortex drawn by Ramon y Cajal. Image from Wikimedia Commons

We’ve known for over a century that sensory cortex is arranged in distinct layers, each containing a different make up of neuronal types and projection patterns, but we don’t actually know that much about the actual computations performed in each layer.  Today a paper from Massimo Scanziani’s lab takes a big step towards cracking the function of the bottom layer (layer 6) in mice. Layer 6 neurons project both to upper cortical layers and to the lateral geniculate nucleus in the thalamus, which itself is the primary input to cortex, and so are primed to play a large modulatory role. Using a monumental combination of optogenetics, intracellular recording, and behavioral testing, the paper convincingly makes the case that layer 6 controls the gain of visual responses of upper layer neurons (i.e. changes the size of their responses without altering their selectivity). Gain control is a fundamental computation in cortex, and has been invoked as a mechanism for attention, perception, spatial processing, and more. The cellular mechanism here is worked out in primary visual cortex, but it could potentially operate throughout layered cortex.

Continue reading →

Telepathy? I think not

Posted on by
1

From Supp Fig 10 of Kay et al.

There is just something about neural decoding that captures the imagination. Scientists “reading out brain activity” to infer what someone was seeing or doing sounds like the stuff of science fiction. But in practice, with the right dataset and right computer algorithm, it can be done – providing the question you are trying to query the brain is simple enough. But no matter how simple the question, with every paper comes an orgy of stories in the mainstream press about how scientists can eavesdrop on your thoughts or even engage in electronic telepathy. Thereby infuriating scientists and science journalists in droves, sometimes detracting from some very cool work.

Today I’m going back a few years to a paper that typifies this effect, a study from Jack Gallant‘s lab about a model for decoding natural images from fMRI activity in early visual cortex.

Continue reading →

Awakening dormant genes with cancer drugs

Posted on by
Reply

From Figure 1 of Huang et al.

Here’s one that first appeared online at the end of last year by Benjamin Philpot, Bryan Roth and Mark Zylka about a finding that could lead to a therapy for Angelman Syndrome. Angelman syndrome is a rare neurodevelopmental disorder affecting 1 in 15,000 live births and is characterized by developmental delay, lack of speech, seizures, and motor difficulties. There are no therapies available for core symptoms and individuals generally require care throughout life. Autism is often diagnosed in Angelman Syndrome individuals, and the same genomic region has been fingered as a culprit in both disorders. Angelman Syndrome is most commonly caused by deletion of a region on the maternal copy of chromosome 15 containing the gene UBE3A, conversely, some forms of autism may also be caused by duplication of this region.

Although we all possess two copies of UBE3A, only the one inherited from the mother is active. Normally, the paternal copy is epigenetically silenced. This means that in Angelman Syndrome there is no functioning copy at all, which has consequences for multiple signaling pathways and brain circuits. The authors of this paper set out to find a workaround: something that could activate the intact, but dormant, paternal copy of UBE3A.  They made a reporter assay from neurons of mice expressing fluorescent paternal UBE3A protein, and performed a large-scale drug screen, testing over 2000 compounds for ones that would activate paternal Ube3A. None of the most likely suspects worked, but an unlikely class of drugs, topoisomerase inhibitors, did so reliably. Even better,  one of the best (topotecan) is already an FDA-approved cancer drug.

Continue reading →