Some reversible brain and behavioral changes from chronic stress

To rattle the rats to the point where their stress response remained demonstrably hyperactive, the researchers exposed the animals to four weeks of varying stressors: moderate electric shocks, being encaged with dominant rats, prolonged dunks in water. Those chronically stressed animals were then compared with nonstressed peers. The stressed rats had no trouble learning a task like pressing a bar to get a food pellet or a squirt of sugar water, but they had difficulty deciding when to stop pressing the bar, as normal rats easily did.

…Happily, the stress-induced changes in behavior and brain appear to be reversible….

But with only four weeks’ vacation in a supportive setting free of bullies and Tasers, the formerly stressed rats looked just like the controls, able to innovate, discriminate and lay off the bar. Atrophied synaptic connections in the decisive regions of the prefrontal cortex resprouted, while the overgrown dendritic vines of the habit-prone sensorimotor striatum retreated.

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8-month-olds understand probabilities

Maybe not news but i thought it was interesting.

Eight-month-old babies were shown a box full of mixed-up Ping-Pong balls: mostly white but with some red ones mixed in. The babies were more surprised, and looked longer and more intently at the experimenter when four red balls and one white ball were taken out of the box — a possible, yet improbable outcome — than when four white balls and a red one were produced.

Frontiers in Neuroscience Journal

The journal, Frontiers in Neuroscience, edited by Idan Segev, has made it Volume 3, issue 1.  Launching last year at the Society for Neuroscience conference, its probably the newest Neuroscience-related journal.

I’m a fan of it because it is an open-access journal featuring a “tiered system” and more.  From their website:

The Frontiers Journal Series is not just another journal. It is a new approach to scientific publishing. As service to scientists, it is driven by researchers for researchers but it also serves the interests of the general public. Frontiers disseminates research in a tiered system that begins with original articles submitted to Specialty Journals. It evaluates research truly democratically and objectively based on the reading activity of the scientific communities and the public. And it drives the most outstanding and relevant research up to the next tier journals, the Field Journals.

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Photoactivatable transcription: Simplicity vs. overengineering

I finally got around to reading the Nature Methods that has been sitting on my coffee table for a few weeks and I was surprised to see an article on photoactivatable transcription using caged doxycycline with standard Tet On/Off genetics. A postdoc in my lab has been suggesting this type of technology for the last few years and speculating about different ways to possibly implement it. What’s so remarkable about this work is the simplicity of the implementation. In our lab (and others), the common assumption has been that the photoactivatable mechanism should be designed such that a recombinase is directly light-activated. (For example, a membrane tethered Cre recombinase where the tether is broken by light and releases the recombinase to the nucleus after illumination.) But that seems a bit overengineered. Is there a simpler way? Yes!

In this work, Cambridge et al. generated a dox analog, cyanodoxycycline, that is better retained inside cells (reduced membrane permeability) and put it inside a stable photoactivatable (UV) cage. Instead of making the system entirely genetic, they use small molecule uncaging (an established technology) to make problem simpler. In this case, standard Tet genetics can be used (thus leveraging existing model organism Tet lines) and the novel caged Dox can be easily added to food, etc. I think this is a great example of finding the simplest solution to a problem that at first seems very complex.

And the uncaging results are quite impressive. Here are two spatial patterns of gene expression in hippocampal slice culture, a smiley face and a single neuron, achieved by clamping down the field stop before illumination:

Picture 3 Picture 4

IARPA and trust detection

Neurodudes reader Jason M. sent me some information about a funding agency, IARPA, or Intelligence Advanced Research Projects Activity, that is funding neuroscience-related research. I had never heard of IARPA before but it has existed since 2006 as something of an intelligence-focused DARPA. There upcoming funding deadline (Aug 21) is for projects on detecting trust signals between humans.

Just last night, I watched the tense but amazing film The Hurt Locker (don’t let the name disuade you, see the phenomenal Metacritic rating), which is about a bomb disposal squad during the recent Iraq War. There is one particularly stirring scene with a suicide bomber who claims that he was forced to wear a vest with explosives and doesn’t want to go through with it. The difficulty in the limited time before the bomb explosion revolves around whether to actually trust the man and the challenge of trusting someone when neither party speaks the other’s language. You can certainly at least understand (putting aside the ethics of war itself) why governments are interested in detecting nonverbal trust cues.

Details about the IARPA call for proposals are after the jump. Continue reading

Inert designer ligand-receptor for genetically targeted activation

Recently, Alexander et al. published Remote Control of Neuronal Activity in Transgenic Mice Expressing Evolved G Protein-Coupled Receptors [Neuron Neurotechniques], in which they use directed evolution techniques to modify a muscarinic GPCR to selectively bind an orally-deliverable small molecule that is otherwise inert. Apparently, this is the first time a channel has been engineered such that is selective for a biologically inert molecule, providing specificity of action. (They compare their technology with the hyperpolarizing allatostatin receptor which can have off-target effects.) Because the channel is specified genetically and the drug circulates systemically, it is easier to activate large populations of neurons (viz. optogenetic methods which are constrained to neurons in the light delivery volume) without implanted devices (eg. cannulas for AlstR, fiber optics for optogenetics, etc.) Another new technique/neurotechnology… onwards marches the innovation of new circuit-cracking tools!