neurodudes

In the September Nature Neuroscience, we have a promising new technique: Millisecond-timescale, genetically targeted optical control of neural activity.

I think several people have suggested doing something like this before but no one has actually done it. What they’ve done is genetically modified (by lentivirus, for those curious) ordinary hippocampal neurons in culture, adding the same photo-electric transducing protein — rhodopsin – found in photoreceptors. Yup. You heard me right. They’ve expressed a cation-channel-gating rhodopsin in ordinary hippocampal neurons. With an standard fluorescence microscope (Xenon lamp + Chroma GFP cube), they can photostimulate single action potentials (and sub-threshold depolarizations) in single neurons.

Now here’s my idea for bioengineers to take this to the next level: Add a second photosensitive protein tied to an inhibitory channel. Ideally, we would want total separation between the stimulating wavelengths for the two different (excitatory, inhibitory) channels. Now, you have a system where all neurons can be directly excited or inhibited with different laser lines. In other words, a network of neurons where all voltages can be fully controlled. Sweet!

This seems like a great tool to add to the existing arsenal of photostimulation techniques (like photoelectric effect-based light-on-silicon stimulation that was pioneered by Goda lab.) Here’s a question: Is this the end of multi-electrode arrays? In slice, we already have single spike detection with Ca-sensitive dyes from Yuste’s lab. Now, we have optical single spike stimulation. Perhaps MEAs will be relegated to the domain implantable devices. Regardless, I’m proud to see several of the authors are from Stanford! Read on for the full abstract. (more…)

PLoS Biology: Evolution at Two Levels: On Genes and Form

An interesting (but speculative) essay that presents evidence suggesting that differences in anatomy are more due to differences in regulatory regions than coding regions of the genome.

The NYT has a nice summary of a recent Cell paper, where investigators from the Karolinska Institute used a wonderfully innovative technique to determine the age of many cells, including neurons from visual cortex and the cerebellum.

The general idea is this: Up until 1963, above ground nuclear weapons testing was allowed, dispersing radioactive carbon (14C) into the atmosphere. This “tagged” carbon was integrated into all plants and animals at that time and, since 1963, at an exponentially decreasing amount. Thus, calibrated with pine tree trunk rings (which are produced every year), the scientists are able to judge the age of cells by seeing how much of the genomic DNA of the cell contains 14C. Genomic DNA is created during cell division and, as the authors show, it appears not to be regenerated since preserved cell specimens from different years show the characteristic exponential decay of 14C post-1963.

The neat finding is that several neurons, from cortex and cerebellum, are very old… in 50-60 year old cadavers, neurons were found that were just as old or nearly just as old as the cadavers. So, even if there is neurogenesis occuring, it is now almost certain that some of our neurons are with us throughout life.

From the WSJ:

HEALTH
As Early as Age 40, Genes in the Brain Begin to Deteriorate
By LAURA JOHANNES, Staff Reporter of THE WALL STREET JOURNAL
June 10, 2004; Page D1

Harvard University researchers found that 20 genes critical for
learning and memory begin to decline in function as early as age 40,
pointing the way for further research aimed at tackling the mental
infirmities that come with growing old.
(more…)