Newfound Molecular Switch Signals a Thumbs-up or Thumbs-down in the Mouse Brain

Kay has wondered why she feels the way she does. Tye has always wanted to know what was happening in the brain. She couldn't find a class in college that explained how electrical impulses through the brain's trillions of connections could lead to feelings. "There wasn't the neuroscience course I wanted to take." The thing didn't exist.

She remembers being criticized for dedicating a chapter of her thesis to emotion. She was told that the study of feelings didn't fit in with behavioral neuroscience. She still disagrees at the time. We don't know where emotions are being implemented.

Tye's research team has taken a step towards understanding the biological basis of such ineffable experiences as loneliness and competitiveness. She and her colleagues discovered that there was a switch in the brain that flags an experience as positive or negative. Tye is still pursuing these questions. Some researchers are thinking the same way. A neuroscientist at the Icahn School of Medicine at Mount Sinai in New York City is not involved in the Nature paper. There is a problem in the field.

There was a switch in the study. If it works the same way in humans, it could help a person hear an ice cream truck instead of a bear. Animals need to act differently in different scenarios in order to survive. The hub is where we translate sensory information into meaning. It will determine whether you survive. It will affect your mental health and your quality of life.

Negative experiences could lead to depression if the switch is changed. The specter of addiction may be raised by an excessive appetite for reward. Stephen Maren of Texas A&M University was not involved in the research. It has been thought of as a disorder of one or the other system. The brain assigns positive and negative values to experiences.

As a graduate student, Tye looked at her study of emotion through the amygdala, a hub of emotional processing inside the brain. At a conference in 2007, she talked about the structure's importance in learning in response to rewards and its role in fear. She believes that there are separate sets of brain cells in the amygdala.

The basolateral amygdala was found in a paper published in 2015. One set was needed for mice to learn that a tone predicts a sip of sugar water, and the other was needed for them to link a noise with an electric shock. The researchers were able to locate the cells using a technique developed by Tye. There was a twist on optogenetics. They are usually activated with light. A way to use optogenetics was devised by Tye.

With the reward and fear tracks out of the way, Tye wondered what the positive or negative "switch" was. The team came up with a clue. When the researchers cataloged the genes that were switched on or expressed in each set of neurons, there was one difference that stood out.

After that clue, Tye and her colleagues mapped out all the cells in the amygdala. Three bunches were found in the brain. In order to figure out which fibers were relevant, the researchers used a technique that had never been done before. Maren says that it was the first time that gene editing had been used to remove this type of neurotransmitter.

Only one population disrupted the mice's ability to associate a tone with sugar or a shock. The set came from the thalamus. Deleting the neurons in the thalamus made mice slower to learn about the reward and faster to shock, as evidenced by behaviors such as running to a spout and freezing. There was a boost in the food response and a reduction in the fear response.

According to the findings, the brain's default state is negative and that the brain needs to be switched to a more positive one. Something to put our brain into a state of relaxation is needed. The system should be able to learn about rewards. I will assume the situation is bad if I don't have it on.

A mystery of timing is solved by neuroscience. Animals can learn to link stimuli that are different in time and distance. Neurological responses, such as those involving glutamate, occur within milliseconds. It's possible to amplify the glutamate signal and prolong it.

Experts say the work could lead to therapies for mental health issues. A drug that makes the brain less active might ease addiction and the reward-seeking behaviors that go along with it. Enhancing neurotensin's actions could make anxious or depressed people see the world in a better light. The target is attractive for many mental health disorders.

Michael Anderson of the University of Cambridge was not involved in the study. He says that the impact may be significant. Anderson says that the more we know about the neural circuitry underlying emotion and conditioning, the more likely we will be able to build on that.

The work extends the hard science of emotion in a number of ways through the invention of new tools. Maren says the work is technical. It is pushing the field in new directions.