Two interesting meetings

Biophysics of Biological Circuits:
From Molecules to Networks
Summer School

Engineering Principles in Biological Systems
Cold Spring Harbor Meeting


A genetically encoded fluorescent amino acid

A genetically encoded fluorescent amino acid — Summerer et al. 103 (26): 9785 — Proceedings of the National Academy of Sciences

Some cool silicon biology to add to the toolbox. Now you can tag proteins by using a nonsense codon that codes for a fluorescent amino acid-tRNA. This technique and similar ones could easily revolutionize cellular tracking of protein trafficking.

Presynaptic somatic membrane potential can influence EPSPs

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.

Curing blindness, with light-activated ion channels?

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


Optical detection via second harmonic generation

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:

much-needed list

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