neurodudes

A FRET-Based Calcium Biosensor with Fast Signal Kinetics and High Fluorescence Change — Mank et al. 90 (5): 1790 — Biophysical Journal

Relevant details (from the discussion):

Above we reported the generation of a FRET-based calcium biosensor employing TnC as calcium-binding moiety that is fast, is stable in imaging experiments, and shows a significantly enhanced fluorescence change. Its off-rate is significantly faster than those of previous double chromophore sensors and even outmatches the fastest single fluorophore sensors to date.

Although it is faster than what was previously available, it would be nice if the off-rate was even faster:

Its off-rate was extremely fast, optimally fitted with a double exponential with a dominating {tau} of 142 ms (A1 = 0.63) and a minor {tau} of 867 ms (A2 = 0.06) (Fig. 2 D). Mutation of the N-cap residue 131 of helix G within TnC from isoleucine to threonine (35Go) yielded an indicator of higher calcium affinity with a Kd of 1.7 µM (Fig. 2 B) and shifted the Hill slope to 1.1, although at reduced maximal fluorescence change of 270%. TN-XL expressed well in primary hippocampal neurons at 37°C. Fluorescence was evenly distributed, filling all neuronal processes, with no signs of aggregation. The nucleus was devoid of fluorescence. Repeated stimulations with high potassium followed by repeated washouts demonstrated stable baselines over long recording sessions and reproducible signals after stimulation. Moreover the signals induced by high potassium were more than doubled compared to TN-L15.

From the Apr 20 issue of Neuron: Integrative Properties of Radial Oblique Dendrites in Hippocampal CA1 Pyramidal Neurons (or, for those who want just the N&V’s summary: Dendritic Enlightenment: Using Patterned Two-Photon Uncaging to Reveal the Secrets of the Brain’s Smallest Dendrites)

The technology is essentially high-speed two photon uncaging of glutamate, but the authors have used it here to create “realistic” patterns of dendritic input in an attempt to see just how dendritic arithmetic works. Although I haven’t read the paper closely, they claim to work out the spatiotemporal parameters underlying dendritic spike generation for pyramidal neurons.

A related methodology paper from a recent J. Neurophys. also uses fast acousto-optic deflectors and two-photon but for imaging purposes. It’s more descriptive about the setup and techniques for those interested in doing this type of work.

In an impressive integrative effort, a new article in this month’s issue of Neuron describes a robust object and face classification model that is consistent with both behavioral and fMRI experiments.

From a preview of the article:

“A central theme that has emerged in research on face perception therefore is whether or not faces are “special” such that the cognitive and neural mechanisms that underlie their processing are different from those underlying the processing of other visual objects. [...] In this issue of Neuron, Jiang et al. (2006) provide a compelling array of evidence supporting the idea that the processing of faces and objects do not rely on qualitatively different mechanisms. In a series of experiments, Jiang et al. present and integrate findings from neural modeling, behavior, and fMRI, showing that face classification, similarly to object classification, can be achieved by a simple-to-complex architecture, based on hierarchical shape detectors. Furthermore, variations of this model can account for both configural and feature-based processing without qualitative modification of the model’s structure.”

The Riesenhuber lab, from which this work comes, has been working on object recognition in an integrative way. The lab is particularly “at the intersection of neuroscience and AI”.

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

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?

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 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.
(more…)

In this nice open-access (ie. free!) essay in October’s PLoS Biology, David Kleinfeld and Oliver Griesbeck describe the revolution in neural recording that is taking electrophysiology from the realm of dark-arts (lots of training) to simpler genetically-encoded, imaging-based techniques. A lot of ground is covered in the article, including the creation of many new colors of fluorescent proteins (XFPs) that can be genetically targeted and the tagging of the XFPs with Ca, voltage, and pH sensors. A nice summary table is included comparing the techniques too:

As you have likely noticed, Bayle and I post heavily about these new recording techniques because of our strong belief that a lot of neuroscience will be enabled by improving our ability to stimulate and record from entire networks of neurons with high resolution. Yesterday, I was listening to one of the many recent neuroscience talks here at MIT in which philosopher Pat Churchland suggested, as many others also have, that the problem of consciousness might be more of an artifact of primitive science than an actual scientific problem. She made a very nice analogy with a problem from centuries ago when scientists were unsure about the existence of life forces and what precisely made an animal alive. Of course, with modern cell biology, we now have a cellular theory of life, disease, and death. (To be fair, Churchland went on to say that people like Christof, Crick et al. are misguided in attempting to study neural correlates of consciousness. I completely disagree with that; at the very least, those scientists are helping to extend our understanding of the visual system and the difference between perception that we are aware of [conscious] and perception that has a neural correlate but that we are not aware of [unconscious]. Honestly, who cares if they say they’re studying consciousness or not — make a judgement based on the science.)

This Is Your Brain Under Hypnosis - New York Times

Very interesting stuff. Subjects were hypnotized and told that days later they would see “gibberish” symbols printed in particular colors. They needed to report back the color that the word appeared in. (For those unfamiliar, the Stroop test presents color words, like “red”, in a different color, such as the word “red” written with green ink. People have difficulty reporting the color of the word because we have a strong need to “read” the written word.)

The highly hypnotizable subjects (grouped according to a predetermined measure) essentially showed no Stroop effect (ie. no reaction time difference with conflicting word and color). And, with fMRI, they saw that normally activated visual-reading areas were not activated in these subjects.