This week’s Nature has quite a few additional halorhodopsin articles for photochannel fans.
Halorhodopsin article from Deisseroth’s lab:
Multimodal fast optical interrogation of neural circuitry [News & Views]
Also, there is an intriguing article on both the general excitement in the neuroscience community with this new technology and a possible intellectual property dispute over it.
Saw this book on the Daily Show a few nights ago and it looked interesting: Survival of the Sickest by Sharon Moalem
The author mentioned a theory of schizophrenia as due to toxoplasma infected cats, who are themselves infected by rats carrying the disease. Apparently, when the rat is infected, the toxoplasma alters the behavior of the rat such that it doesn’t run away from a cat. So, the parasite ensures its survival.
Although I’m not a big fan of just-so evolutionary explanations in general, this book sounds like it might be a fun read.
Ed strikes again!
Two-Color, Bi-Directional Optical Voltage Control of Genetically-Targeted Neurons
Having found a powerful method for activating neurons with blue light in the protein Channelrhodopsin-2 (ChR2) [1], we sought to augment the toolbox by finding a single-component system capable of mediating light-elicited neuronal inhibition. We identified a powerful tool, the mammalian codon-optimized version of the light-driven chloride pump halorhodopsin, from the archaebacterium Natronobacterium pharaonis (here abbreviated Halo) [2].
Im a molecular/cellular neurobiologist. I do however, have a deep interst in neural prosthetics, bionics research. Is there a place for me in this field?
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.
Fascinating evidence pointing toward a treatment for parkinson’s. Basically, Lindquist’s group finds that overexpression of a trafficking protein Rab1 that moves folded proteins from the ER to the Golgi can prevent alpha-synuclein accumulation-triggered death of rat neurons.
Of course, in vitro is not in vivo. And, for all we know, Parkinson’s could be a complex, multi-mechanism disease. But this looks promising!
Abstract:
Alpha-synuclein misfolding is associated with several devastating neurodegenerative disorders including Parkinson’s Disease (PD). In yeast cells and in neurons {alpha}Syn accumulation is cytotoxic, but little is known about its normal function or pathobiology. The earliest defect following {alpha}Syn expression in yeast was a block in endoplasmic reticulum (ER) to Golgi vesicular trafficking. In a genome-wide screen, the largest class of toxicity modifiers were proteins functioning at this same step, including the Rab GTPase Ypt1p, which associated with cytoplasmic {alpha}Syn inclusions. Elevated expression of Rab1, the mammalian YPT1 homolog, protected against {alpha}Syn-induced dopaminergic neuron loss in animal models of PD. Thus synucleinopathies may result from disruptions in basic cellular functions that interface with the unique biology of particular neurons to make them especially vulnerable.
An Anti-Addiction Pill? - New York Times
Lots of interesting stuff here on new treatments for addiction, including: A methadone (heroin-substitute) replacement called buprenorphine with less dependency and less of a high; an injectible version of alcoholism treatment naltrexone called Vivitrol, which is injectable and lasts one month; some medications that increase GABA production; and, perhaps most innovative is a vaccine against nicotine that allows antibodies to bind nicotine and prevent crossing through the blood-brain barrier.
Excerpts with some of the neat experiments involving dopamine receptors and environmental factors in addiction are after the jump.
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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.
Not directly neuroscience-related but this is a pretty cool paper nonetheless. Basically, the authors use automated pattern recognition to pick out small strings in the “non-coding” regions of the human genome. They show that these pyknons are found at regular distances within coding regions and UTRs. Even more intriguing is that
approx. 40% of the known microRNAs are similar to 689 pyknons and that the pyknons subsume 56 of the 72 recently reported 3′ UTR motifs, lending further support to the possibility of a connection between the pyknons and RNAi/PTGS.
Both RNAi (RNA interference) and PTGS (post-transcriptional gene silencing) have recently been found to be major regulatory mechanisms for endogenous gene silencing and regulation. Here’s a link to a primer on PTGS and RNAi.
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