Monthly Archives: July 2012

An “electro-endoscope” for combined imaging, photocontrol and electrical recording

Sending light and recording electrical activity in deep brain structures using optrodes

When optogenetic tools for controlling neural activity came into play in the late 2000s, it became obvious that hybrid probes for delivering light into the brain and recording photoevoked activity simultaneously would become a basic component of the optogenetic toolkit. And this for at least two reasons. First, microelectrode recordings are still the golden standard for measuring neuronal firing, surpassing by far optical sensors at least at the single cell resolution and millisecond time scale. And second, electrical recordings are and will probably remain the ultimate readout of the efficiency of optogenetic activation and inactivation protocols. In other words, the only way to show that your optogenetic activator or silencer does the job is to directly record its effects on neuronal firing.

Various types of optical⁄electrical probes for deep brain photostimulation and recording. Top left: An optical⁄electrical probe having single optical fiber and single electrode. Bottom: Three types of single optical fiber–multiple electrode combination. Bottom left – wire-wound tetrodes are combined with an optical fiber. Bottom center – “Michigan probe” integrated with an optical fiber. Bottom right – “Utah” multi-electrode array combined with a tapered optical … Continue reading

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A reason to prefer Arch over Halo?

In the last few years, several strategies for silencing neurons optogenetically have emerged. The most popular approaches make use of two types of microbial light-driven ion pumps. One type is an optimized version of halorhodopsin, an inward chloride pump isolated from the halophilic bacterium Natronomonas pharaonis. Over the past couple years, halorhodopsin was tweaked by adding a series of trafficking signals to improve its addressing to the cytoplasmic membrane (Gradinaru et al, 2010). The latest version is eNpHR3.0. The other type corresponds to archeorhodopsins, which are outward proton pumps isolated from halophilic archaebacteria of the genus Halorubrum. The two popular archeorhodopsins are Arch from Halorubrum sodomense and ArchT from Halorubrum genus (Chow et al., 2010, Han et al., 2011). The same optimization tricks used for halorhodopsin also worked for Arch and ArchT. Both types of pumps generate a hyperpolarizing current in mammalian neurons in response to 500-600 nm light and are effective optogenetic silencers of neuronal activity.

A recent head-to-head comparison performed in the lab of K. Deisseroth has shown that, under matched experiments conditions, archeorhodopsins seem to perform slightly better than the best available halorhodopsin mutant (Mattis et al., 2012). In particular eArchT3.0 (an enhanced version of ArchT) generates about … Continue reading

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