What happens when we give up?
Inside the brain, a group of cells known as nociceptin neurons get very active before a mouse's breakpoint. They emit nociceptin, a complex molecule that suppresses dopamine, a chemical largely associated with motivation. The findings, reported in Cell, offer new insight into the complex world of motivation and reward.
The nociceptin neurons are located near an area of the brain known as the ventral tegmental area. The VTA contains neurons that release dopamine during pleasurable activities. Although scientists have previously studied the effects of fast, simple neurotransmitters on dopamine neurons, this study is among the first to describe the effects of this complex nociception modulatory system.
"We are taking an entirely new angle on an area of the brain known as VTA," said co-lead author. "The big discovery is that large complex neurotransmitters known as neuropeptides have a very robust effect on animal behavior by acting on the VTA," said the author.
The discovery came by looking at the neurons in mice seeking sucrose. The mice had to poke their snout into a port to get sucrose. At first it was easy, then it became two pokes, then five, increasing exponentially, and so on. Eventually, all the mice gave up. Neural activity recordings revealed that these "demotivation" or "frustration" neurons became most active when mice stopped seeking sucrose.
Optogenetic and chemogenetic activation of nociception neurons caused avoidance and decreased motivation for rewards.
In mammals, the neural circuits that underlie reward seeking are regulated by mechanisms to keep homeostasis - the tendency to maintain internal stability to compensate for environmental changes. In the wild, animals are less motivated to seek rewards in environments where resources are scarce. Persistence in seeking uncertain rewards can be disadvantageous due to risky exposure to predators or from energy expenditure, the researchers noted.
Deficits within these regulatory processes in humans can manifest as behavioral dysfunctions, including depression, addiction, and eating disorders.
"We might think of different scenarios where people aren't motivated like depression and block these neurons and receptors to help them feel better," the senior author said. "That's what's powerful about discovering these cells. Neuropsychiatric diseases that impact motivation could be improved."
Looking to the future, the author said, these neurons could perhaps be modified in people seeking drugs or those that have other addictions.
https://newsroom.uw.edu/news/researchers-discover-science-behind-giving
https://www.cell.com/cell/fulltext/S0092-8674(19)30737-8
The science behind giving up!
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