neurodudes

There’s been some work recently on looking at second harmonic generation for optical readout of action potentials… any opinions on this work?

First a brief primer on SHG (from Yuste’s recent Nature Methods paper on fluorescence microscopy):

In SHG, high-infrared light intensity drives the lowest-order nonlinear polarizability of molecules (or groups of molecules) in the specimen so that coherent light of exactly double frequency (or half the wavelength) is emitted. Because the process can occur away from resonance frequencies, there is no absorption of light, thus avoiding complications of photochemistry. This phenomenon is rare and requires, like two-photon excitation, a high concentration of photons at the focal point, something that also gives it optical sectioning. SHG is particularly interesting because it only occurs where chromophores are oriented in noncentrosymmetric arrays, such as chromophores adsorbed to biological membranes or other chemical interfaces. Thus, SHG is perhaps the only optical technique that is truly sensitive to biological membranes, something which makes it ideal for detecting changes in membrane potential. As many important biological processes, such as electrophysiological communication, detection and transduction of external molecules and cell-cell interactions occur at plasma membranes, SHG is likely to become a very useful tool for biologists.

Seed papers:

• Overcoming photodamage in second-harmonic generation microscopy: Real-time optical recording of neuronal action potentials [PNAS Open Access, Feb 2006] , L. Sacconi, D. A. Dombeck, and W. W. Webb
• Imaging membrane potential in dendritic spines [PNAS, Jan 2006] , Mutsuo Nuriya, Jiang Jiang, Boaz Nemet, Kenneth B. Eisenthal, and Rafael Yuste

This article in the latest issue of the Journal of Neuroscience is interesting in the sense that they are do human brain stimulation of the hypothalamus, for the treatment of cluster headaches - but they then do positron emission tomography (PET) to examine the downstream neural circuits responsible for the abolition of the perception of headache.

Hypothalamic Deep Brain Stimulation in Positron Emission Tomography

This moves the field of brain stimulation from simple stimulate-and-see-what-happens, towards more of a study of human neural circuitry and how stimulation drives activity in connected locations. It’s possible this will lead, in the future, to better and more focal stimulation protocols, as people figure out what the “circuit-level” phenomena are that correct particular aspects of neural dysfunction. Perhaps someday we will have a map of the “hot spots” where stimulation of a small chunk of matter can modulate a wide degree of neural circuitry for the better.

(Last year, Helen Mayberg and colleagues’ deep-brain-stimulation-and-depression paper got at this issue as well, in which they stimulate the cingulate and (perhaps surprisingly) sent depressed patients into remission, and furthermore changed the activity of frontal structures from the abnormal state, back to a more normal pattern of activity.)

These studies are perhaps setting a good precedent for brain-stimulating neuroclinicians to follow.

— Ed

Nature Neuroscience’s editorial board posts a call for a change (doi:10.1038/nn0406-457) in the incentive structure of neuroscience in favor of funding initiatives that foster synthesis.

A quote from the article:

“To shift the emphasis toward quality rather than quantity of scientific results, funding agencies could support specific integrative initiatives, such as large-scale meta-analyses in unresolved areas or experiments to tackle particularly contentious conflicts in the existing literature.”

It goes on:

“Simply having more time to think and interact with colleagues could foster consolidation and conceptual breakthroughs. Unfortunately for many academic researchers, such ruminating might carry the stigma of inactivity or, worse, speculation. However, science is largely a creative process, and the minds of scientists are ultimately its greatest resource. Legitimizing time for creative synthetic thought through funding might be an inexpensive way to shift the current incentive structure.”

This could be the beginning of an important change in the culture of the field.

A recent study in the Journal of Cognitive Neuroscience has isolated activation in the brain during a 3-stage model of deductive reasoning.

The study shows that during the ‘premise processing’ stage, there is more activity in occipito-temporal areas. During the ‘integration phase’, anterior prefrontal cortex is more active. During the final ‘valdiation phase’, the find more activity in posterior parietal and prefrontal areas.

AI started working on reasoning early on. Will studies like this lead us to the next advance in building models of reasoning?

Berkeley researchers lay groundwork for cell version of DNA chip

This is a little off the beaten path, but I think that the Neurodudes crowd is generally interested in techniques related to neuron-to-silicon interfacing. Here’s some neat surface chemistry from Livermore Labs that facilitates binding of DNA oligos to the cell surface. Then, just like with a gene chip, you can link cells with the right (complementary) oligos to a pre-coated chip.

My first reaction to this was, Wow, another great application of the homologous base pairing machinery of nucleic acids. I’m amazed by the out-of-the-box thinking in this idea — sticking DNA to the outside of the cell. According to the article, the authors estimate that about 270,000 DNA molecules are put on the surface of each cell by their process. (Though I’m sure they’ve looked at it, one does wonder how this impacts membrane trafficking, receptor internalization processes, etc.)

Let me emphasize… This is totally cool! This allows cell-type-specific micropatterning at the level of whatever your chip printing resolution is. (Traditionally, gene chips are “spotted” using precision multi-head inkjet-like printers.) For you cell culture enthusiasts out there, you might imagine a cell culture where you have many different cell types and have full control (down to a single cell!) of where each type of cell is placed. Talk about a co-culture!

I’ve been thumbing through pubmed, online resources, and lab members’ collective consciences looking for a complete list of pharmacological agents acting on receptors (i.e. metabotropic glutamate receptors), phenomena (i.e. AMPA receptor desensitization), and any other players that can affect neurotransmission at the synapse. No such list seems to exist.

So, if you have some knowledge to contribute, please add to this list of agents and effects on a new wiki page. Warning: the current format is really simple (any improvements would be welcome), but it’s a first pass at a much needed electrophysiology resource.

— davematthews

Rein on pain lays mainly in the brain, researchers find

People looking at their own anterior cingulate are able to control their pain. Neat.

Importantly, here are the controls cited in the press release:

Researchers used multiple control groups to ensure against this: The first remained outside the MRI machine; the second received no imaging feedback; the third was shown different areas of the brain that don’t process pain; and members of the fourth group were shown someone else’s brain activity. None of the control subjects showed an ability to control pain levels.

Full PNAS article here. (free via Open Access)

When Bad People Are Punished, Men Smile (but Women Don’t) - New York Times

I think there has been studies similar to this before… here’s the relevant details:

Furthermore, researchers found that the brain’s pleasure centers lit up in males when just punishment was meted out.

The researchers cautioned that it was not clear if men and women are born with divergent responses to revenge or if their social experiences generate the responses.

A neat example of how really understanding a scientific tool can lead to innovation of a simpler version. In this case, a PCR thermocycler (for amplifying nucleic acids, like DNA) was built with a glass slide and some wire! Normally, I wouldn’t post such a process-specific tool as a PCR machine, but I love the simplicity of the idea.

Junkyard PCR - Nature Methods

Remember when a thermocycler was the most expensive equipment in your lab? This may no longer be the case, but even so, the idea of building your own PCR equipment out of a rubber sheet, a glass slide and a bit of wire may sound like something from an episode of ‘MacGyver’. Nonetheless, a pair of German scientists have done just that, proving that reality can still occasionally get the edge on fiction.

A Resilient, Low-Frequency, Small-World Human Brain Functional Network with Highly Connected Association Cortical Hubs (Achard et al., 2006)

A study on network properties of the whole brain (functional connectivity data from fMRI)… interesting to see this type of work published in J. Neurosci. Building on previous fMRI/whole brain connectivity studies, the authors use a set of wavelet basis functions to estimate the correlations between different anatomical regions.

Also includes some analyses on resiliency of the system (via a metric like “largest connected cluster”) to random and targeted attack (ie. node deletion). It would be neat if they also did some analysis of common stroke damage. I would think that a stroke probably doesn’t qualify as a “targeted attack”, in the traditional sense, but, due to the predefined structure of the major circulatory structures (eg. circle of Willis), there are likely regions that are near the most commonly blocked arteries, etc. Perhaps someone with some medical qualifications could weigh in here?

There is also a nice discussion of why the human brain does not appear to be a scale-free network: That nodes do not seem to follow the “rich-get-richer” rule of preferential attachment. Evolutionarily recent structures like prefrontal seem to be among the hubs of the system and older structures like limbic regions do not dominate. Here’s a picture of the connectivity map from the paper:

Full abstract after the jump.
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