Further evidence of this bias comes from the reaction of the mice when they were first put into learning situations. Before they knew whether the new associations would be positive or negative, the release of neurotensin from their thalamic neurons decreased. The researchers speculate that new stimuli are assigned a more negative valence automatically until their context is more certain and can redeem them.
“You’re more responsive to negative experiences versus positive experiences,” Hao Li said. If you almost get hit by a car, you’ll probably remember that for a very long time, but if you eat something delicious, that memory is likely to fade in a few days.
Ryan is more wary of extending such interpretations to humans. “We’re dealing with laboratory mice who are brought up in very, very impoverished environments and have very particular genetic backgrounds,” he said.
Still, he said it would be interesting to determine in future experiments whether fear is the actual default state of the human brain—and if that varies for different species, or even for individuals with different life experiences and stress levels.
The findings are also a great example of how integrated the brain is, Wen Li said: The amygdala needs the thalamus, and the thalamus likely needs signals from elsewhere. It would be interesting to know which neurons in the brain are feeding signals to the thalamus.
A recent study published in Nature Communications found that a single fear memory can be encoded in more than one region of the brain. Which circuits are involved probably depends on the memory. For example, neurotensin is probably less crucial for encoding memories that don’t have much emotion attached to them, such as the “declarative” memories that form when you learn vocabulary.
For Tasker, the clear-cut relationship that Tye’s study found between a single molecule, a function, and a behavior was very impressive. “It’s rare to find a one-to-one relationship between a signal and a behavior, or a circuit and a function,” Tasker said.
Neuropsychiatric Targets
The crispness of the roles of neurotensin and the thalamic neurons in assigning valence might make them ideal targets for drugs aimed at treating neuropsychiatric disorders. In theory, if you can fix the valence assignment, you might be able to treat the disease, Hao Li said.
It’s not clear whether therapeutic drugs targeting neurotensin could change the valence of an already formed memory. But that’s the hope, Namburi said.
Pharmacologically, this won’t be easy. “Peptides are notoriously difficult to work with,” Tasker said, because they don’t cross the blood-brain barrier that insulates the brain against foreign materials and fluctuations in blood chemistry. But it’s not impossible, and the field is very much headed toward developing targeted drugs, he said.
Our understanding of how the brain assigns valence still has important gaps. It’s not clear, for example, which receptors the neurotensin is binding to in amygdala neurons to flip the valence switch. “That will bother me until it is filled,” Tye said.
Too much is also still unknown about how problematic valence assignments may drive anxiety, addiction, or depression, said Hao Li, who was recently appointed as an assistant professor at Northwestern University and is planning to explore some of these questions further in his new lab. Beyond neurotensin, there are many other neuropeptides in the brain that are potential targets for interventions, Hao Li said. We just don’t know what they all do. He’s also curious to know how the brain would react to a more ambiguous situation in which it wasn’t clear whether the experience was good or bad.
These questions linger in Hao Li’s brain long after he packs up and goes home for the night. Now that he knows which network of chatty cells in his brain drives the emotions he feels, he jokes with friends about his brain pumping out neurotensin or holding it back in response to every bit of good or bad news.
“It’s clear that this is biology, it happens to everyone,” he said. That “makes me feel better when I’m in a bad mood.”
Original story reprinted with permission from Quanta Magazine, an editorially independent publication of the Simons Foundation whose mission is to enhance public understanding of science by covering research developments and trends in mathematics and the physical and life sciences.
