Optogenetics confirms that strengthened connections between neurons fuel memories


Using optogenetics, University of California, San Diego (UCSD) scientists inactivated and then reactivated a memory in genetically engineered rats. The study, supported by the National Institutes of Health (NIH; Bethesda, MD), is the first cause-and-effect evidence that strengthened connections between neurons are what fuel a memory.

Related: Light triggering demonstrates that memory engrams are physical phenomena

Optogenetics uses low-level light to selectively activate proteins administered to live tissues. It adapts the same cellular machinery that allows primitive organisms like algae to be controlled by light from the sun to control specific brain circuit components instantly with a laser—even in a behaving animal.

"Our results add to mounting evidence that the brain represents a memory by forming assemblies of neurons with strengthened connections, or synapses," explains Roberto Malinow, MD, Ph.D., of UCSD, a grantee of NIH's National Institute of Mental Health (NIMH). "Further, the findings suggest that weakening synapses likely disassembles neuronal assemblies to inactivate a memory."

"Beyond potential applications in disorders of memory deficiency, such as dementia, this improved understanding of how memory works may hold clues to taking control of runaway emotional memories in mental illnesses, such as post-traumatic stress disorder," said NIMH director Thomas R. Insel, MD.

Neuroscientists have long suspected that strengthened connections between neurons—called long-term potentiation (LTP)—underlies memory formation. But proof had remained elusive—until now. The research team proved it by detecting LTP when forming a memory, removing the memory with a process known to reverse LTP, and then bringing the memory back via LTP—all by modifying the strength of synapses in a memory circuit.
 
In conventional rodent fear conditioning experiments, a tone is paired with a foot shock to induce a fear memory of the tone.  If the memory is active, the animal freezes and shows reduced reward-seeking behaviors when it hears the tone. Instead of the tone, Malinow's team paired the shock with direct optogenetic stimulation, lighting up a specific group of neurons in a known auditory fear memory circuit.

Such precise targeting wasn't possible with earlier electrical stimulation techniques. "It is just a jungle in the brain—too many nerve cells coming through in any one place," explains Malinow.

By varying the pattern of optogenetic stimulation, the researchers were able to strengthen connections between neurons in the circuit by promoting LTP or weaken the connections by promoting a countervailing process called long-term depression (LTD). This made it possible to readily form a fear memory, remove it, and then bring it back.

Moreover, upon closer optogenetic probing in postmortem brains, the targeted circuit neurons showed telltale changes in sensitivity of brain chemical messenger systems. These changes confirmed the hypothesized role of strengthening and weakening of synaptic connections in the switching on-and-off of the memory.

"We have shown that the damaging products that build up in the brains of Alzheimer's disease patients can weaken synapses in the same way that we weakened synapses to remove a memory," says Malinow. "So this line of research could suggest ways to intervene in the process."

"In addition to eliminating any doubt about a link between LTP/LTD with memories, this work highlights the staggering potential of precision targeting and circuit manipulation for alleviating maladaptive memories," says project officer Chiiko Asanuma, Ph.D., of the NIMH Division of Neuroscience and Basic Behavioral Science.

"This work provides a nice demonstration of how the field of neuroscience is being transformed by the types of technologies that are at the heart of President Obama's BRAIN Initiative," says Edmund Talley, Ph.D., program director at NIH's National Institute on Neurological Disorders and Stroke (NINDS).

Full details of the work appear in the journal Nature; for more information, please visit http://www.nature.com/nature/journal/vaop/ncurrent/full/nature13294.html.

-----

Don't miss Strategies in Biophotonics, a conference and exhibition dedicated to development and commercialization of bio-optics and biophotonics technologies!

Follow us on Twitter, 'like' us on Facebook, and join our group on LinkedIn

Subscribe now to BioOptics World magazine; it's free!

POST A COMMENT

Related Articles

Photoacoustic imaging pioneer Lihong Wang

Photoacoustic imaging pioneer is 2015 Britton Chance Biomedical Optics Award winner

Photoacoustic imaging innovator Lihong Wang, whose research enables noninvasive examination of tissues inside the body at deep levels, has been awarded the 2015 Britton Chance Biomedical Optics Awa...

Light microscopy method speeds brain, spinal cord measurements

Researchers at the University of Miami (Florida), as a part of the Miami Project to Cure Paralysis, have turned to a light microscopy method to help answer questions that help define human spinal c...

Light microscopy trailblazers win Nobel Prize in Chemistry 2014

Three light microscopy pioneers—Eric Betzig, Stefan W. Hell, and William E. Moerner—have been awarded the Nobel Prize in Chemistry 2014 for two separate achievements in breaking the optical diffrac...

Laser neurosurgery tool receives Health Canada license as Class 4 medical device

Monteris Medical's NeuroBlate system, a minimally invasive robotic laser thermotherapy tool, has received Health Canada License as a Class 4 Medical Device.

BLOGS

BioOptics World editor-in-chief Barbara Goode

What is biophotonics?

At BioOptics World, our focus is photonics (including optics) for life sciences—that is, biophoto...

Nobel Prize honors super-resolution optical microscopy

"This year's prize is about how the optical microscope became a nanoscope," said Staffa...

High-res 3D optical: A tribute to Mats Gustafsson

Biologists will soon be able to see more in 3D, thanks to the Howard Hughes Medical Institute (HH...

Most Popular Articles


CONNECT WITH US

            

Twitter- BioOptics World

Copyright © 2007-2014. PennWell Corporation, Tulsa, OK. All Rights Reserved.PRIVACY POLICY | TERMS AND CONDITIONS