In a groundbreaking new study, researchers at the University of California, San Diego erased and then reactivated memories by stimulating neurons in the brains of genetically engineered rats with a series of light pulses that have been previously shown to strengthen or weaken the connections between brain cells. This is the first study to be able to directly show that the strengthening or weakening of these connections, called synapses, is the underlying basis for memory. The study has been published in Nature.
Neurons communicate with each other via synapses, which are the tiny gaps between cells that permit the flow of information in the form of a chemical or electrical signal. Early research found that repeated electrical stimulation of neurons within a brain region called the hippocampus enhanced the ability of these cells to communicate with neighbors. This process is called long-term potentiation (LTP), and it has long been suspected that this is the underlying basis of memory formation. Despite decades of research, however, no one has unequivocally demonstrated that this is the case.
For this study, a team of researchers led by UCSD neuroscientist Roberto Manilow first engineered rats so that their brain cells produced a light sensitive protein which could be activated by a pulse of light delivered by an optical fiber implanted into the brain. They then used this optogenetics to condition the rats to associate pain with optical stimulation by delivering light pulses to certain neuronal populations and then shocking the rats. The rats quickly began to associate the optical stimulation with pain and displayed fear responses when the neurons were stimulated. The scientists were able to demonstrate telltale signs of LTP by looking at chemical changes in the neurons.
Next, the team stimulated the same neurons but with a different, low-frequency sequence of light pulses that had been previously demonstrated to reverse LTP by weakening the synaptic connections, which is known as long-term depression (LTD). When the mice were given the optical stimulation that they originally associated with pain they no longer elicited a fear response, suggesting that the original memory was erased. The team was able to then reactivate the memories by delivering high-frequency light pulses that triggered LTP, and then erase them again. “We were playing with memory like a yo-yo,” Manilow said in a news-release.
The results of this study are therefore finally able to demonstrate a causal link between LTP, LTD and memory. “We can cause an animal to have fear and then not have fear and then to have fear again by stimulating the nerves at frequencies that strengthen or weaken the synapses,” said lead author Sadegh Nabavi in a news-release.
This discovery may also have applications in the field of Alzheimer’s research since, according to Manilow, the beta-amyloid protein fragment that builds up in the brains of Alzheimer’s patients also weakens synapses in a similar manner to how the low-frequency stimulation in this study removed memories. “So this line of research could suggest ways to intervene in this process,” he added.