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Encoding Your Basolateral Amygdala....


.....or, Whatever Makes You Happy (!).......

An excerpt:

A new study from MIT finds that these emotions are controlled by two populations of neurons that are genetically programmed to encode memories of either fearful or pleasurable events. Furthermore, these sets of cells inhibit each other, suggesting that an imbalance between these populations may be responsible for disorders such as depression and post-traumatic stress disorder.

“The positive memory cells identified by the genetic markers, which counter negative memory cells, promise an opportunity to identify effective molecular targets for treatment of emotional disorders such as depression and PTSD,” says Susumu Tonegawa, the Picower Professor of Biology and Neuroscience and director of the RIKEN-MIT Center for Neural Circuit Genetics at the Picower Institute for Learning and Memory.

Tonegawa is the senior author of the study, which appears in the Oct. 17 issue of Nature Neuroscience. Joshua Kim, an MIT graduate student, is the paper’s lead author.

Distinct populations

In 2014, Tonegawa’s lab identified a brain circuit that links memories with positive or negative emotions. This circuit connects neurons in the hippocampus, which remember the memory’s context (what happened and where it happened), with neurons in the basolateral amygdala (BLA), which stores the emotional association of the event.

In that study, the researchers also showed that they could reverse a memory’s emotional associations, in mice. To achieve that, they artificially activated hippocampal cells that had been storing a negative memory, while the mouse was undergoing a happier experience. This weakened the fear association of the original memory and replaced it with a more positive feeling, as indicated by the mouse’s preference for a certain location in its container.

However, the same strategy had no effect on neurons of the BLA, suggesting those neurons are precommitted to encoding either fear or feelings of reward. “They seem fixed in terms of what behaviors they can drive,” Kim says.

In the new study, Tonegawa’s lab set out to identify genetic differences that could be used to distinguish the fear-responsive and reward-responsive populations. After analyzing all of the genes turned on in BLA cells, they came up with one gene that is found in BLA cells that encode positive memories but not in cells that encode negative memories. They also found another that exclusively marks the negative population.

The gene associated with reward neurons, known as ppp1r1b, is a well-known gene whose product is involved in dopamine signaling, which is necessary for feelings of pleasure. The function of the gene associated with fear neurons, rspo2, is unknown.

“We don’t know what they’re doing exactly,” Kim says. “There should theoretically be a connection between the gene and cell function, but we don’t necessarily have to understand what the genes do. We’re just using them to discriminate the two populations.”

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