Two neurons of the basolateral amygdala. MIT neuroscientists have found that these neurons play a key role in separating information about positive and negative experiences. Credit: Anna Beyeler and Praneeth Namburi
A new study reveals how 2 populations of neurons contribute to the brain’s inability to correctly assign emotional associations to events, eg those who are depressed often do not feel happy even when experiencing something that they normally enjoy. Learning how this information is routed and misrouted could shed light on mental illnesses including depression, addiction, anxiety, and posttraumatic stress disorder.
In a previous study, Tye’s lab identified 2 populations of neurons involved in processing positive and negative emotions. One of these populations relays information to the nucleus accumbens, which plays a role in learning to seek rewarding experiences, while the other sends input to the centromedial amygdala.
In the new study, the researchers wanted to find out what those neurons actually do as an animal reacts to a frightening or pleasurable stimulus. To do that, they first tagged each population with a light-sensitive protein called channelrhodopsin. In 3 groups of mice, they labeled cells projecting to the nucleus accumbens, the centromedial amygdala, and a third population that connects to the ventral hippocampus. Tye’s lab has previously shown that the connection to the ventral hippocampus is involved in anxiety. Tagging the neurons is necessary because the populations that project to different targets are otherwise indistinguishable. “As far as we can tell they’re heavily intermingled,” Tye says. “Unlike some other regions of the brain, there is no topographical separation based on where they go.”
They trained the mice to discriminate between 2 different sounds, one associated with a reward (sugar water) and the other associated with a bitter taste (quinine). They then recorded electrical activity from each group of neurons as the mice encountered the two stimuli. This technique allows scientists to compare the brain’s anatomy and its physiology.
The neurons within each subpopulation did not all respond the same way. Some responded to one cue and some responded to the other, and some responded to both. Some neurons were excited by the cue while others were inhibited. “The neurons within each projection are very heterogeneous. They don’t all do the same thing,” Tye says.
However, despite these differences, there were patterns for each population. Among the neurons that project to the nucleus accumbens, most were excited by the rewarding stimulus and did not respond to the aversive one. Among neurons that project to the central amygdala, most were excited by the aversive cue but not the rewarding cue. Among neurons that project to the ventral hippocampus, the neurons appeared to be more balanced between responding to the positive and negative cues.
The findings suggest that to fully understand how the brain processes emotions, neuroscientists will have to delve deeper into more specific populations, Tye says.
Another question still remaining is why these different populations are intermingled in the amygdala. One hypothesis is that the cells responding to different inputs need to be able to quickly interact with each other, coordinating responses to an urgent signal, such as an alert that danger is present. “We are exploring the interactions between these different projections, and we think that could be a key to how we so quickly select an appropriate action when we’re presented with a stimulus,” Tye says.
In the long term, the researchers hope their work will lead to new therapies for mental illnesses. “The first step is to define the circuits and then try to go in animal models of these pathologies and see how these circuits are functioning differently. Then we can try to develop strategies to restore them and try to translate that to human patients,” says Beyeler. http://news.mit.edu/2016/brain-processes-emotions-mental-illness-depression-0331
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