A Science Driven Life

An un-edited blog about science, discovery, technology, travel and the occasional whiskey

Posts Tagged ‘science

Dendrite Pruning and Optical Methods in Neuroscience

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Screen Shot 2014-04-03 at 11.07.57 AMAs always this is meant to be a brief overview of a paper (and the methods used in neuroscience) I happened to have found interesting- for more details please refer to the manuscript itself.

I enjoyed reading a relatively recent paper published in Science from group in Japan (Kazuo Emoto, The University of Tokyo)  that suggests a role for Ca2+ signaling in dendritic pruning, a house-cleaning function in neurons that has been shown to be very important in learning and memory, as well as experience and some forms of cognitive deficits (such as autism and neurodegeneration).

Dendrites are highly branched areas of the cell that act as antennae receive information from neighboring cell.  Pruning refers to a highly complex, regulated, activity dependent process in which connections that are non-essential to the formation of the developing brain are cleaved.

In pruning, our neurons clean house.  Unnecessary connections formed during development are trashed as a way to reduce clutter and improve accuracy and efficiency of signaling.  Many of the basic mechanisms behind how pruning works have been identified.  Specific cascades of enzymes (caspases) as well as a key self-destruction pathway (proteosome-ubiquitin) work together to rid individual neurons of unnecessary connections.  While a lot is known about the processes that regulate the pruning, very little is known about the signaling that tells which dendritic arbors (branches of dendrites) are to be pruned and which of those is to be kept as a part of the neural network.

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Written by Michael Mohammadi

April 15, 2014 at 15:37

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

Science Technique: Making brains clear – bringing clarity to fluorescence imaging and CLARITY!

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Screen Shot 2013-04-11 at 12.32.23 AM

Image from Chung et al, 2013 – Nature

by Michael Mohammadi

Clear Lipid-echanged Acrylamide-hybridized (Anatomically) Rigid Imaging/Immunostaining/In situ hybridization-compatible Tissue-hYdrogel.

Or just CLARITY.  Whatever you call it, this newly published research technique from Karl Deisseroth and colleagues at Stanford University will allow scientists to image far deeper into fixed tissue than ever before.  The images are absolutely stunning.  A youtube video (below) of the data resulting from the first publicatoin on CLARITY went viral on the internet last week and a feature article appeared in the NY Times as well as a number of science sites and blogs.   The majority of these give a brief overview of CLARITY and the implications of the work.  Here I will focus on how scientists make things look colorful, why we do it, and what CLARITY has done to make some really cool and exciting pictures.  I hope to make scientific imaging as well as CLARITY approachable to the non-scientist. Read the rest of this entry »

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 »