A Science Driven Life

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Archive for the ‘Optogenetics’ Category

Brief review: Simultaneous two-color optogenetics using novel probes (Klapoetke et al., 2014)

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Cartoon structure of rhodopsin – Wikipedia Commons

To catch up on the field of optogenetics, here is a primer and here is an update on some new stuff.  Also refer to the literature (Mattis et al., 2011; Fenno et al., 2011).  This post assumes a working understanding of Optogenetics, Electrophysiology and some genetics.

A recent paper out of MIT (Ed Boyden lab) identifies two new probes in the ever growing quest to find improve optogenetic tools that will allow for greater spectral separation of activation/excitation wavelengths.  Some of the major challenges for optogenetics research are:

  • genetically expressing opsins, or other light sensitive molecules in model organisms/specific cells
  • finding the right probe that addresses a specific need (i.e. high frequency stimulation, or activate a specific Gi/o pathway)
  • delivering light of a specific wavelength to a particular target in tissue and/or specific cell types
  • spectrally separating a single probe (i.e. ChR2 activated at 470nm) from an imaging probe (i.e. GCamp3, or even the new RCamp which can be activated by blue light)
  • finding two or more probes to express that will not “cross-talk”- such that excitation wavelength of probe 1 will not activate probe 2

Optogenetics allows for very precise control of cell excitability and/or signaling pathways and researchers continue to push the limit of the existing tools and pharmacological agents.  For instance, if studying the interaction of interneurons in the hippocampus area CA1 it would be beneficial to be able to simultaneously activate CCK interneurons while optically inhibiting PV interneurons, or vice versa.  There are currently methods of blocking one versus the other (machR agonist carbachol for instance activates CCK only) but to rapidly be able to control the activity of these neurons would be of great interest in studying the details of synaptic transmission of individual or small groups of neurons (worth noting is these types of on/off, two wavelength probes exist for other applications such as PIF-2.

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Written by Michael Mohammadi

March 31, 2014 at 05:17

Targeting Light: Two recent papers that use active illumination!

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Screen Shot 2014-03-20 at 5.02.10 PMIn my day job I get to travel quite a bit and visit labs around the world who use methods in microscopy in imaging.  These labs range from neuroscience to developmental biology and everything in between, and many of these labs have very specific needs when it comes to light delivery.  The applications I most often work with can involve from high power lasers for ablation and thrombosis, or FRAP or photoconversion.  I’m very focused on optogenetics and uncaging, as well as any type of imaging, especially the use of genetically encoded indicators (for voltage, ions, temperature, pH, etc).  

While many people tend to use a simple configuration for single spot/point illumination, or full field illumination (and we provide these tools as well) where we are unique is in systems that allow for “targeted” or “active illumination.”  There are many methods for targeting light (possibly a good topic for an upcoming review) but the two of the main methods used are either using a galvo-mirror system (very fast mirrors that move a single spot of light in X-Y to create regions with the ability to target to a diffraction limited spot) or a digital micromirror device, or DMD.  

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Written by Michael Mohammadi

March 20, 2014 at 16:04

Optogenetics / Optophysiology References Page on SDL!

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Dear friends,

I am compiling optogenetics, optophysiology and advanced imaging references and will be organizing them by category/field.  I have launched the page and over the next week it will grow to contain all papers I can find in a given field.  Where possible I will post links to the articles for download and in some cases will post comments and footnotes on the research.

Science Publications / Reference Page

I will also have a page with references of the “Latest and Greatest” papers that I find interesting.  This will focus on “Advanced Online” publications and things that are hot off the press!

I’m very excited for this endeavor and am open to ideas and suggestions on how to improve the format and organizing.

I’m very behind on about 5-6 paper reviews I began writing, expect a lot of activity in the coming weeks!



Written by Michael Mohammadi

February 20, 2014 at 23:31

Quick Look: Another use for optogenetics and GPCR signaling

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Optogenetics is the rapidly emerging field in biotechnology and biological sciences that combines the genetic expression of light sensitive molecules and the delivery of light to control cells, populations of cells or animal behavior.  Often when we think of optogenetics, the first thought is back to the landmark papers where light was used to depolarize cells and cause action potentials (Zemelman et al. 2002, Boyden et al. 2005).  While these types of studies are highly prevalent in neuroscience today, a whole other branch of optogenetics exists that uses light sensitive molecules to modulate some biochemical or second messanger pathway.  One area, called OptoXRs, is of great interest as therapeautic targets for a variety of pharmaceutical products as a majority of these act through some type of g-protein coupled receptor (GPCR) pathway.


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Written by Michael Mohammadi

September 9, 2013 at 19:56

Science in press: A look at two recent papers- Optogenetics to control GPCRs and optogenetics in monkeys!

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English: Based on PDB 1hzx and the Heller/Schaefer/Schulten lipid bilayer coordinates.

English: Based on PDB 1hzx and the Heller/Schaefer/Schulten lipid bilayer coordinates.

by Michael Mohammadi

Being free from the “chains” of academia I have been able to expand my scientific interests well beyond NMDA receptor signaling and short term memory.  I do miss actually producing research from time to time, but I now average 6 papers read in a week which is about double (or more) what I read in grad school so I’m still feel like I’m part of the process.  I do have the luxury of spending a lot of time in planes and on trains, both excellent venues for diving into a paper with few distractions (Bose noise canceling headphones are essential!).  I have found that it is liberating to be able to read articles from all different fields of science and not be limited to a very specific field or research question.  Exploring new research in neuroscience, physiology, physics, optics, imaging and more has really rejuvenated my spirit for science and discovery, a spirit that had faded over the long duration of wrapping up my dissertation.  Now that this curiosity and excitement is back and fully charged, I hope to share some of the cool papers I’m reading with you.  It is my goal with this “Science in press” series that I review a few papers that I have read in the last few weeks that really stood out.  These may be a bit more technical than my other articles, but I hope to keep it accessible to the mainstream reader.  As always, questions are encouraged.

For this first installment I tried to cover 5 papers I read recently, but I ended up a bit too excited and went into a lot of detail on paper one.  I’ll try to be more concise in the future if it’s more interesting to get into the details let me know, I would enjoy writing either way!  So I ended up giving overviews of two recent papers in Nature Neuroscience.

I welcome criticisms and feedback, suggestions on papers to read, as well as corrections to my interpretations or explanations of the experimental design, results or conclusions.  I accept I may get things wrong and hope to learn from my readers.  Without further ado…

1.  Optical control of metabotropic glutamate receptors. Levitz et al, 2013 Nature Neuroscience

I’ll start with a recent paper that employs optogenetics for something other than direct gating of ion channels!  Dr. Ehud Isacoff’s group at UC Berkely has been doing some amazing work in the field of molecular engineering with optical probes (among other things).  Previous work included a very cool probe called HyLighter (of which some data was acquired with the Mosaic) that is a light-activated glutamate channel that selectively gates K+.  In this most recent paper, Levitz et al describe a metabotropic glutamate receptor (mGluR) which is a specific type of G-Protein Coupled Receptor (GPCR; the most abundant receptor type in the body) that they have engineered to respond to specific wavelengths of light which results in a variety of downstream G-protein regulated outputs. Read the rest of this entry »

Science Techniques: What is optogenetics and why is it so trendy?

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by Michael Mohammadi

Screen Shot 2013-03-25 at 8.25.20 AM

Fun with an argon-ion and he-ne laser. |Source=[http://www.flickr.com/photos/28042570@N08/2648853050/ Beams in Fog + Car Windshield] * Uploaded by PDTillman

Pour a nice hot cup of your morning coffee and grab a recent issue of Nature, or Science, or Neuron and scan the table of contents.  I’ll bet you your next cup of Joe that at least one article in that issue (if not more) have some sort of optogenetic approach to address complicated questions in neuroscience and cell signaling.  “Optogenetics” is a very trendy term in science these days and for good reason.  It has been described as a way for researchers to take over your brain, provide bionic vision, possibly treat epilepsy, and for the founding researchers in the field, a way to cash in on big financial prizes.  With all the excitement, there is still some misunderstanding about how the technique works and exactly why it’s relevant.  I hope to answer both of these questions here without getting overly technical.

“Optogenetics” refers to a relatively new field that combines molecular biology with light stimulation to allow researchers (and someday clinicians) to have precise control over the behavior of a cell, populations of cells, or even a whole animal.

In this video we see a mouse that becomes hyperactive 
when blue light activates Channelrhodopsin-2 in its brain:  

Optogenetics: The basics

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Written by Michael Mohammadi

March 25, 2013 at 09:00