Erasing Cue-Associated Memories

2019-04-26T18:49:54-07:00 April 26th, 2019|Biology, Health and Medicine, Neurobiology|

By Neha Madugala, Cognitive Science, ‘22

Author’s Note: While working on a different paper, I became interested in treatment and therapy for drug addiction. Addiction continues to increase, yet there seem to be limited viable options to actually overcome this problem. One of the main issues in the recovery process is relapses. I found this study interesting and promising for drug therapy because it directly targets relapses, an important step in preventing and treating drug addiction more effectively.

In order to reduce the rate of addiction, scientists are trying to figure out how to prevent relapses after an individual has decided to stop using a specific drug. One of the major factors in preventing relapses is breaking detrimental environmental connections that may trigger an individual to start using a certain drug again.

A study by Torregrossa at the University Pittsburgh School of Medicine identified the brain circuit involved in cue-associated memories. They were able to establish that synaptic connections between the medial geniculate nucleus (MGN) and the lateral amygdala (LA) were strengthened with increased cocaine usage (3). Furthermore, they found that by weakening the synaptic connections in the MGN-LA circuit, they were able to erase the cocaine-cue memories and in turn help reduce relapses.

The MGN is a group of subnuclei located in the thalamus that receive auditory input, which it then conveys to the auditory cortex (4). The LA is an important component to conditioning experiments, like Torregrossa’s experiment. Though the LA is usually associated with experiments that use fear-inducing stimuli, Torregrossa uses a more desirable incentive: the cocaine high. It also believed that the LA is a key site of plasticity, which means it establishes long-lasting changes while learning these cues and also helps store cue-associated memories (6). Based on these findings, Torregrossa developed an experiment that reflected the role of both the MGN and the LA in the circuit to test whether the link between a cue and a certain situation could be altered. She used the scope of drug addiction to see if relapses triggered by cue-associated memories could be prevented by erasing the link between the cue and memory.

The researchers placed the rats in a cage with a lever, which connected to a pump that intravenously dispensed a dose of cocaine into the rat’s bloodstream. Every time the rat pressed the lever, it was given a dose of cocaine, which was accompanied by a bright light and a ringing noise for ten seconds (7). The goal was to establish an audiovisual cue with the high felt from cocaine. By creating this connection, Torregrossa would be able to simply play the audiovisual cue and stimulate a craving for the cocaine high, even when no cocaine was being dispensed from the lever.

The creation of the audiovisual cue strengthened the synaptic connections in the MGN-LA circuit, establishing a starting point for Torregrossa to determine whether these strengthened connections could be diminished or altered in some form. The goal of the experiment was to weaken these connections in order to break the linkage between the established audiovisual cue and the cocaine high.

In order to weaken the connections, Torregrossa used optogenetics, a technique to introduce light-sensitive genes into targeted brain cells in order to control brain activity using light signals (8). Optogenetics essentially introduces genetically modified neurons, achieved through the insertion of light-sensitive proteins into the targeted neurons, which create ion channels among the genetically modified neurons. Through the use of a specific type of light, for this experiment – blue LED laser light, researchers are able to stimulate the light-sensitive ion channels on command (8). This techniques have been utilized in previous experiments with mice where researchers were able to stop epileptic seizures or induce thirst on command (7).

Light stimulation must take place in the region, which is activated when new memories are made (2). Furthermore, Torregrossa et al. observed that the memory of the cocaine high as a result of the audiovisual cue led to heightened activity in the rat’s amygdala, which is located in the medial temporal lobe and is crucial in processing emotions such as fear and pleasure (1). As a result, Torregrossa identified the amygdala to be a key site in weakening the connection between the cue and the high.

She determined that the sensory intersection in the amygdala would be the ideal site to place the electrode, given that it is directly associated with the cue-triggered memories. The electrode inserts light-sensitive proteins into the targeted neurons. Therefore, these electrodes enable the blue LED laser light to control the neurons (3). For this experiment, the light can dampen the drug cue. After using the light stimulation for fifteen minutes, they conducted a test to determine any changes in the strength of the synaptic connections.

By reducing the extent of the drug cue, the mice essentially forgot the link between the audiovisual cue and the cocaine high (7). In addition to the optogenetics method, Torregrossa initially used exposure therapies. The goal of exposure therapy is in line with Torregrossa’s intent to break the link between the cue and source of addiction. However, exposure therapy involves exposing the mice to the audiovisual cue without the cocaine high a significant number of times, so they in turn do not associate the cue with the high. While this method may be temporarily effective, once the environment changes, researchers have observed that the connection between the cue and source of addiction returns (3). While both exposure therapy and the optogenetics method were successful in reducing relapses, the optogenetic method was more effective in terms of accuracy and long-term results (3).  

The possibility of erasing cue-associated memories has the potential to help prevent relapses and improve therapy and treatment for addiction. By establishing the amygdala as a key site of where these connections are produced, researchers will be able to conduct further studies looking at what other parts of the brain are involved in the creation of these memories. Furthermore, the success of optogenetics in this experiment suggests that optogenetics may be a viable option in the future to break these cue-associated memories essentially erasing memories (7). The ethics behind being able to erase these associations and in turn a memory is still vague. As more research is done on the MGN-LA circuits, researchers will be able to improve addiction therapy and also establish ethical rules in order to ensure that these new findings are used in a morally sound manner.

 

Works Cited

  1. “Amygdala.” ScienceDaily, ScienceDaily, www.sciencedaily.com/terms/amygdala.htm.
  2. Dougherty, Stephen. “How to Use Light to Control the Brain.” Scientific American, 27 Mar. 2012, www.scientificamerican.com/article/how-to-use-light-to-control-the-brain/.
  3. “Erasing Memories Associated with Cocaine Use Reduces Drug Seeking Behavior.” ScienceDaily, ScienceDaily, 22 Jan. 2019, www.sciencedaily.com/releases/2019/01/190122115001.htm.
  4. “Medial Geniculate Nucleus.” NeuroImage, Academic Press, www.sciencedirect.com/topics/neuroscience/medial-geniculate-nucleus.
  5. PhD, Catharine Paddock. “Cocaine Addiction: Could Targeting This Brain Circuit Prevent Relapse?” Medical News Today, MediLexicon International, 24 Jan. 2019, www.medicalnewstoday.com/articles/324277.php.
  6. Schafe, Glenn E., et al. “Tracking the Fear Engram: The Lateral Amygdala Is an Essential Locus of Fear Memory Storage.” Journal of Neuroscience, Society for Neuroscience, 26 Oct. 2005, www.jneurosci.org/content/25/43/10010.
  7. Specktor, Brandon. “Could ‘Memory-Erasing’ Implants Help Prevent Drug Relapses? It Worked for These Rats.” LiveScience, Purch, 24 Jan. 2019, www.livescience.com/64580-cocaine-rats-memory-erased.html.
  8. “Optogenetics | Definition of Optogenetics in English by Oxford Dictionaries.” Oxford Dictionaries | English, Oxford Dictionaries, en.oxforddictionaries.com/definition/optogenetics.