neurodudes

Modulation of intracortical synaptic potentials by presynaptic somatic membrane potential : Nature

Very interesting work. Modulation of the somatic potential seems to influence the EPSP, as measured by paired patch recordings of two layer 5 cells in cortical slice. Somatic depolarization from resting potential to near threshold results in an increase in evoked EPSPs.

In synaptic physiology, we often make a point of distinguishing intrinsic changes (eg. membrane potential) from synaptic conductance changes. Now it looks like the line between those might be a bit blurry!

Here’s a N&V by Eve Marder too.

Online methods share insider tricks : Nature

This is such a good idea. It is always about the voodoo:

Perhaps more importantly, it is the subtle variations — the deftness of touch, the type of mixing tube, and a dash of hocus-pocus — that distinguish a successful experiment from a flop. But such details often exist only as scrawled footnotes or collective laboratory wisdom. “The art of the science really is not present in many of these protocols,” says geneticist Garry Nolan of Stanford University, California, who has put his protocols online. “They don’t tell people what the voodoo is.”

The websites could help share the voodoo. They are loosely based on the online encyclopaedia Wikipedia, which lets users edit each other’s entries. Unlike the protocols already available online, the idea is to create a repository of experiments and the tricks needed to do them, and allow users to add their own.

ScienceDaily: Semiconductor Brain: Nerve Tissue Interfaced With A Computer Chip

From the article:

16384 transistors on an area of one square millimeter record the neural activity in the brain.

Hmmm, that sounds like a lot of transistors… what kind of voltage sensing resolution can a device like that provide? Well, that works out to 1.6 transistors per 10 square microns, which is arguably the relevant area for a neuron. Although these are extracellular signals, this high-resolution tool is going to have quite a large impact.

From the abstract:

We report on the recording of electrical activity in cultured hippocampal slices by a multi-transistor array (MTA) with 16384 elements. Time-resolved imaging is achieved with a resolution of 7.8 µm on an area of 1 mm2 at 2 kHz. A read-out of fewer elements allows an enhanced time resolution. Individual transistor signals are caused by local evoked field potentials. They agree with micropipette measurements in amplitude and shape. The spatial continuity of the records provides time-resolved images of evoked field potentials and allows the detection of functional correlations over large distances. As examples, fast propagating waves of presynaptic action potentials are recorded as well as patterns of excitatory postsynaptic potentials across and along cornu ammonis.

M. Hutzler, A. Lambacher, B. Eversmann, M. Jenkner, R. Thewes, and P. Fromherz: High- resolution multi-transistor array recording of electrical field potentials in cultured brain slices. Journal of Neuropyhsiology. Preprint online (May 10, 2006).

The original article (whichs seems to online in a preprint form) has excellent photos of the array (showing how it can cover a lot of a hippocampal slice), the tight correspondence between the transistor signal and a microelectrode field signal, and some cool readouts of the “whole hippocampus” with various blockers. I doubt anyone has ever been able to simultaneously do such fine scale electrophysiology on such a large portion of the mammalian brain ever before.

Synaptic tuning : Nature Reviews Neuroscience

For those interested in neuromodulators:

Treatment of striatal neurons with a D1 receptor agonist led to an increase in the dendritic staining intensity of NMDA receptor NR2B subunits. There was also an increase in the association of NR2B subunits with PSD-95 — a scaffold protein required for the assembly of NMDA receptors — and in the surface localization of NR2B-containing receptors.

Original article in J. Neurosci. from Dunah and colleagues. An excerpt from the original aricle of a neat application of FRET continues after the jump.
(more…)

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.

Weak pairwise correlations imply strongly correlated network states in a neural population : Nature

Very few MEA studies make it into Nature, so this definitely got my attention.

Often in neuroscience we are confronted with a small sample measurement of a few neurons from a large population. Although many have assumed, few have actually asked: What are we missing here? What does recording a few neurons really tell you about the entire network?

Using an elegant prep (retina on a MEA viewing defined scenes/stimuli), Segev, Bialek, and students show that statistical physics models that assume pairwise correlations (but disregard any higher order phenomena) perform very well in modeling the data. This indicates a certain redundancy exists in the neural code. The results are also replicated with cultured cortical neurons on a MEA.

Some key ideas from the paper are presented after the jump. (more…)

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”.

How would you cure blindness, if your phototransducing rods and cones had degenerated - as happens in syndromes that affect millions of people worldwide? A lot of investigators have tried to create very complicated electrical stimulators that drive patterned activity in the retina. You need a power source, a camera of sorts, a computational element, and an array of electrodes that can crank out precise, well-timed current pulses, for a long time. It’s a heroic piece of optical and electrical engineering.

But what if you just made other cells in the retina light-sensitive? Channelrhodopsin and other light-activated ion channels have opened up this new kind of endeavor.

Investigators at Wayne State University, the Pennsylvania College of Optometry, and Beijing University have now done this. They expressed Channelrhodopsin in retinal ganglion cells (RGCs) of mice with photoreceptor degeneration. Remarkably, for months afterwards, the RGCs were able to transmit visual information all the way to visual cortex. In mice without channelrhodopsin, these visual evoked responses were never seen. A very impressive piece of systems bioengineering.

Ectopic Expression of a Microbial-Type Rhodopsin Restores Visual Responses in Mice with Photoreceptor Degeneration
Anding Bi, Jinjuan Cui, Yu-Ping Ma, Elena Olshevskaya, Mingliang Pu, Alexander M. Dizhoor, and Zhuo-Hua Pan

— Ed

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