Autism, synapses and mice – pairs division

Posted on 19 Jun 2012 by I-han Chou

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 →

Positive feedback drives network (and manuscript) maturation.

Posted on 30 May 2012 by Noah Gray

Whole-brain anatomical mapping of D1-Cre expression in inhibitory neurons (from Supp Fig.2)

It really is an embarrassment of riches here at Nature these days, what with so many excellent neuroscience-related studies emerging. Just in the last couple of weeks, we’ve had the following studies:

So really, a lot to write about from a science perspective. However, this blog is dedicated to bringing you the editorial back-story, so I wanted to touch on yet another interesting study, published in print today. This new paper offers an opportunity to discuss an important editorial issue: the manuscript appeal process. For more details, you can always read the appropriate section in our guide to authors. But it’s often helpful to follow a particular [successful] example in order to illustrate the process. Continue reading →

“There is no spoon…”: Paralyzed fish navigates virtual environment while we watch its brain

Posted on 10 May 2012 by Noah Gray

Overlaid on the micrograph of the fish is a slice of its brain measured with a laser scanning microscope, in which single neurons are visible.{credit}(courtesy of Ahrens et al.){/credit}

Sometimes an experiment will just reach off the page and slap you in the face, demanding attention. This happens to me every so often and I must admit, our latest paper from the lab of Florien Engert induced such an experience. There have been several cool, technical tours-de-force (is that proper grammar??) over the last few years involving different creatures navigating in a virtual environment while neuronal activity was monitored. These include a mouse running on a spherical treadmill, as well as a fly marching along a similar treadmill-style ball. But in these examples, having the subject head-fixed (for the stability of recordings in the brain, either with electrodes or through imaging) was moderately non-intrusive since walking motions were independent of the head. The same can’t be said for the subject in this latest example of a virtual reality navigator: a wriggling, swimming fish. Therefore, a more creative solution had to be sought and in a paper published online yesterday, Ahrens, Engert and colleagues decided that paralysis was the way to go in order to follow the neural activity of this navigating fish. Continue reading →

Fear of the Light

Posted on 22 Mar 2012 by Noah Gray

**PLEASE SEE UPDATES BELOW**

It is commonly believed that distinct mini-networks of neurons, firing together, may be the means by which memories and other conceptual encoding requirements are handled in the brain. However, it is only recently that we have had the tools available to directly test the sufficiency of such a mechanism. Today, a new study in Nature from the lab of Susumu Tonegawa documents the ability to use light as a means to activate distinct subsets of neurons responsible for the encoding of fear memories.

Continue reading →

The Fine Architecture of Learning and Joint Publication

Posted on 09 Mar 2012 by Noah Gray

(image courtesy of Svoboda lab, https://openwiki.janelia.org/wiki/display/SvobodaLab/Research)

You warily walk into a dark compartment, wondering if there is food inside. Suddenly there is a loud tone and you feel an uncomfortable surge of electricity through your feet. This goes without saying, but it won’t take long before you will learn to be afraid of that tone. However, over time, you hear the tone without the shock, and slowly (foolishly??) accept that the previous connection may no longer hold.

Or perhaps you are extremely motivated to work for food, given that in your home area, nutrition has been sparse and hard to come by. You see millet seeds seemingly just within the reach of your fore-limb. Though not a typical movement for you, you reach for it. In another instance, you find a different type of food that is difficult to handle. However, it is nourishment nonetheless, so you will learn the required motor skills.

SPOILER ALERT: In each of the above cases, you were a mouse the whole time (I know!) But this is a neuroscience blog, not M.Night Shyamalan’s IMDB page, so perhaps we should focus on what was taking place in the brain as each scenario played out. In both of the cases above, learning was occurring, with new information stored away within the appropriate neural connections of particular brain areas. These situations are on display in a pair of new(ish) papers out in Nature, exploring the structural substrates of such learning and identifying patterns underlying the observed structural changes as learning occurred. Continue reading →

Patients help bring the study of Alzheimer’s to the dish

Posted on 25 Jan 2012 by Noah Gray

Israel et al. Supp Fig1: Experimental design.

Alzheimer’s disease (AD) is a devastating neurodegenerative disease that could become an even more massive public health problem than it already is, if current projections hold. Some predict that by 2050, 1 in 85 individuals will be affected by the disease. Currently, there is no cure, but there are neurotransmitter-enhancement-based strategies to slow down the cognitive deficits [the loss of cholinergic neurons is implicated in some of the memory problems associated with AD so therefore, pharmacological enhancement of brain acetylcholine concentration can partially alleviate some memory-based symptoms.] However, as with many neurodegenerative diseases, these stop-gap treatments only work for so long, until the cells responding to neurotransmitter supplementation treatments die off completely. Therefore, diverse strategies designed to cure or at least slow down AD are imperative.

While a number of AD transgenic mouse models have been created, based on the various mutations identified in patients, the trouble is that these models still utilize the cross-species approach of studying “diseased” mouse neurons expressing mutated human genes. And perhaps an even bigger problem with many mouse models, genetically-inherited forms of AD represent only ~0.1% of cases, with the remainder being “sporadic” (although there are genetic risk factors influencing the emergence of sporadic AD.)