Science fiction comes closer to reality with a new experiment in which scientists used optical/gene-based technology involving a flash of light to inactivate then reactivate a memory in genetically engineered rats. They report their findings in the journal Nature.
The researchers, led by Dr. Roberto Malinow of the University of California-San Diego, say their study is the first to show evidence that strengthened connections between neurons in the brain are involved in memory.
National Institute of Mental Health (NIMH) Director Dr. Thomas R. Insel says:
“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.”
Although it has long been thought that long-term potentiation (LTP) – strengthened connections between neurons – governs the formation of memories, the team notes that until their study, there had not been proof of this.
In order to provide evidence, Dr. Malinow and his team modified the strength of synapses in a memory circuit.
They did this by identifying LTP when a memory formed and removing the memory with a process that reverses LTP. They then brought the memory back through LTP.
The researchers used a new tool in the field of neuroscience: optogenetics.
This works by adapting the cellular mechanisms that allow basic organisms like algae to be controlled by the sun’s light. In their experiment, however, the team controlled specific circuit components in animals with a laser.
They note that in typical fear-conditioning studies, a tone paired with a foot shock in rodents prompts fear when the tone sounds in the future. When the memory is active in the rodent, it freezes at the sound of the tone.
But in their experiment, Dr. Malinow and colleagues coupled the shock with optogenetic stimulation, which lit up a group of neurons in a brain circuit linked with auditory fear memory.
“It’s just a jungle in the brain – too many nerve cells coming through in any one place,” says Dr. Malinow, explaining why earlier electrical stimulation techniques were not able to target these circuits precisely.
When they varied the pattern of the optogenetic stimulation, he and his team strengthened neuron connections by promoting LTP. Additionally, using a process called long-term depression (LTD), they were able to weaken the connections.
What this means is that they were able to remove a fear memory in the rats and then bring it back.
Dr. Malinow says:
“Our results add to mounting evidence that the brain represents a memory by forming assemblies of neurons with strengthened connections, or synapses. Further, the findings suggest that weakening synapses likely disassembles neuronal assemblies to inactivate a memory.”
After they more closely probed the postmortem brains with optogenetics, the team found that the targeted neurons exhibited changes in sensitivity of brain chemical messenger systems.
They say such changes confirm the role of strengthening and weakening synaptic connections in switching memory on and off.
“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 Dr. Malinow.
He suggests their line of research could yield ways of intervening in the process of weakened synapses in such patients.
Chijko Asanuma, PhD, of the NIMH Division of Neuroscience and Basic Behavioral Science, says:
”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.”
The study was funded by the NIMH.
Medical News Today recently reported on a study that suggested narrowing of the carotid arteries could lead to memory and thinking problems.