Rewarding and fearful experiences alter the activity of distinct neurons located in a part of the amygdala
We can recollect several terrifying and pleasant memories with vivid details. But how does the brain process positive or negative emotions at the neuronal network level? Psychiatric disorders such as Major Depressive Disorder, Post-Traumatic Stress Disorder, Addiction etc. have been attributed to perturbations in emotional processing.
The basolateral amygdala (BLA) is a part of the bilaterally located amygdalae (singular; amygdala), found deep inside the brain. It is generally associated with the emotional tagging of various events. Although the BLA has generally been associated with processing fear, recent work has indicated that it could be involved with processing reward also. However, the neuronal circuitries associated with the processing of these two opposing emotions are not anatomically isolated or distinct. How the intertwined neurons in this small region process positive and negative emotions and affect the resulting behaviors remained a mystery.
Kay Tye’s colleagues, led by Praneeth Namburi and Anna Beyeler, came up with an idea to identify the relevant neurons based on previous literature. They then explored the functioning of these neurons and the associated behaviors. The findings of their study were published in the April 29 issue of Nature.
The BLA projects its neurons to other brain regions, including the nucleus accumbens and the centromedial amygdala, which are categorized as reward and fear centers respectively. Tye’s team injected two different dyes into these two regions in mice. The dyes traced the entire neurons, all the way back to their cell bodies in the BLA. The scientists could then visualize the BLA projections to the two regions.
These mice were then fear or reward trained. They either received sucrose (reward learning) or were delivered a foot shock (fear learning) after a sound cue repeatedly. It was seen that reward learning strengthened the neuronal activity in the reward center projections and weakened the activity in the fear center projections. Correspondingly, fear learning strengthened the activity in the fear center projections and weakened the same in the reward center projections.
“There are sensory inputs coming in to either of these populations, and once learning happens, you’re shifting the flood onto one population or the other,” Namburi says.
Tye’s team also used high end techniques like optogenetics to manipulate these neurons and affirm their findings. Optogenetics uses light flashes to manipulate neuronal activity in genetically engineered animals. They observed that stimulating the reward center projections enhanced positive reinforcement while stimulating the fear center projections enhanced negative reinforcement. Also, inhibiting the fear center projections not only impaired fear learning but also enhanced reward learning. These findings reinforced the results mentioned above.
The team, from MIT’s Picower Institute for Learning and Memory, continued with characterizing these two circuits. They found differences in gene expression related to neuronal responses to neurotransmitters. “This represents a new paradigm for therapeutic development,” Tye says. “‘Circuit-based drug discovery’ relies on first identifying how different components of the circuit work and then identifying what targets might control them.”