A Science Driven Life

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Archive for the ‘Genetics’ Category

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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Rhodopsin-transducin

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