How Does the Brain Stay Vigilant?

What They Did: A team of researchers from MIT led by NYSCF – Robertson Neuroscience Investigator and Associate Professor in Brain and Cognitive Sciences Kay Tye, PhD, studied how the brain responds when it senses the presence of a potential threat. 

What They Found: The team discovered that, in rats, when the brain perceives a threat, it releases a neurotransmitter called dopamine in a part of the brain called the prefrontal cortex, which then stimulates the brain to enhance its focus on the possible danger.

Why It Matters: This newly-identified circuit could play a role in anxious and paranoid behavior in humans, with problems in its function potentially leading to symptoms associated with schizophrenia, anxiety, and depression.

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The brain receives a lot of information, and how we process and react to that information matters, especially in the face of danger. An animal that hears the footsteps of a potential predator knows to switch into hyper-vigilance mode, dropping other pursuits to devote its attention to the possible threat. But how does the brain modulate this response? What causes it to override other inputs in favor of preparing for danger?

In a new study published in Nature, a team of scientists at MIT led by NYSCF – Robertson Neuroscience Investigator and Associate Professor in Brain and Cognitive Sciences Kay Tye, PhD, explored what happens in the brains of rats when they detect a threat, finding that the perception of potential danger causes a brain circuit controlled by a neurotransmitter called dopamine to kick into action.

The circuit begins with a part of the brain called the prefrontal cortex. The prefrontal cortex controls a variety of cognitive processes (like decision making and social behavior) and also acts as a sort of “neural switchboard” that can send information on to other parts of the brain. Among the different groups of neurons that live in the prefrontal cortex is one that sends information on to the nucleus accumbens (the brain’s reward center) and one that sends information on to the periaqueductal gray (which modulates defensive behaviors like freezing or running).

The researchers were interested in examining what happens when dopamine—a neurotransmitter that is typically released when the brain senses a threat— hits these two different groups of neurons. To explore this question, the team looked at the behavior of rats who were trained to respond to two different cues: one associated with sugar water (which prompts the rats to run to a port where it is stored), and one associated with an electrical shock (which prompts them to freeze).

When both cues were presented at the same time and dopamine release was stimulated, the rats were more likely to freeze than to pursue the sugar water. Stimulating dopamine and presenting just one of the cues did not affect the rats’ behavior (they ran to the port during the sugar water cue and froze during the shock cue). This suggests that when multiple sources of salient information are present—one of which indicates possible threat—dopamine prompts the brain to drop everything else and focus on preparing for danger.

This circuit may also play a role in neuropsychiatric disorders in humans such as schizophrenia or depression. Dr. Tye suspects that if too much dopamine is released when a threat is sensed, then the brain could overreact, leading to symptoms like paranoia or anxiety that often accompany such disorders. With a better understanding of how the circuit that controls threat response works, we can then create treatments that target these symptoms.