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Optogenetics

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Madison Barker

on 26 October 2014

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Transcript of Optogenetics

The study of neurogenesis in the dentate gyrus using optogenetics for the deactivation of new neurons
Neuron
Dentate Gyrus
Episodic memory
Spacial behavior
Large amount of adult neurogenesis
Neurogenesis- the formation of new cells in the brain
Increased through exercise
Limited to this region and the olfactory bulbs (smell)
Can be turned on and off
Depolarization- turn on
Hyper-polarization- turn off
Pumping H+ ions out of the cell hyperpolarizes the cell
Halorhodopsin Gene
Halobacteria
Type of archaea
Contain halorhodopsin-a transmembrane ion channel that is activated by light and allows chloride ions to enter the cell
Transgenics
How Do We Do This?
Able to target a gene to a specific place
Can breed mice that express halorhodopsin channels in the new neurons of the dentate gyrus
Purpose
Be able to target new neurons and deactivate them
Study the function of new neurons in the dentate gyrus
Why is neurogenesis increased by exercise?
What behavior will be changed by the deactivation?
Optogenetics
The use of light to activate or deactivate cells using specific channels
By activating proton pumps, the cell can be hyper-polarized (shut off)
Temporary (no compensatory measures)
Challenges
How do we target these cells?
We cannot destroy the cells
Other brain regions compensate
Solution- Put them "offline"
Methods
1. Create transgenic mice expressing the channels
2. Genotype the mice
3. Check for "leaky" expression using GFP
4. Insert micro-LEDs that will activate the channels
5. Check for cFos expression
6. Behavioral tests after the model has been proven
Micro-LEDs
Incredibly small light emitting diodes
Placed into the brain a few weeks before testing
Wireless
Will emit light at a wavelength of 570nm to activate the channels
By Madison Barker
Cells can not be destroyed
The brain will compensate
How do we control the cells?
How do we target specific cells without "leakage"?
How do we test for this leakage?
Challenges
Transgenic lines have been bred
Surgery procedure has been tested
Micro-LEDs have been tested for functionality and lifespan

Progress
Gene Therapy
Leber's Congenital Amaurosis
Parkinson's Disease
Epilepsy
Brain Mapping
Could lead to improved therapies, medications, and discoveries
Future Applications
Clark, P.j., W.j. Brzezinska, M.w. Thomas, N.a. Ryzhenko, S.a. Toshkov, and J.s. Rhodes. "Intact
Neurogenesis Is Required for Benefits of Exercise on Spatial Memory but Not Motor
Performance or Contextual Fear Conditioning in C57BL/6J Mice." Neuroscience 155.4
(2008): 1048-058.
Gould E (2007) How widespread is adult neurogenesis in mammals? Nature Rev Neuroscience
8: 481-8.
"4.1.1 Neuron Basics." Neuron Basics. N.p., n.d. Web. 08 May 2014.
Oliver, Rochelle. "» Brain Size Plays Key Role in ADHD - Psych Central News." Psych Central.com. N.p., May 2010. Web. 08 May 2014.
Rhodes, Justin S., Henriette Van Praag, Susan Jeffrey, Isabelle Girard, Gordon S. Mitchell, Jr.
Garland Theodore, and Fred H. Gage. "Exercise Increases Hippocampal Neurogenesis to
High Levels but Does Not Improve Spatial Learning in Mice Bred for Increased Voluntary
Wheel Running." Behavioral Neuroscience 117.5 (2003): 1006-016.
Ting, Jonathan T., and Guoping Feng. "Development of Transgenic Animals for Optogenetic
Manipulation of Mammalian Nervous System Function: Progress and Prospects for
Behavioral Neuroscience." Behavioural Brain Research 255 (2013): 3-18.
Voigts, Jakob, Joshua H. Siegle, Dominique L. Pritchett, and Christopher I. Moore. "The
FlexDrive: An Ultra-light Implant for Optical Control and Highly Parallel Chronic Recording
of Neuronal Ensembles in Freely Moving Mice." Frontiers in Systems Neuroscience 7
(2013): n. pag.
References
Hippocampus
Dentate Gyrus
Full transcript