Why do we stay afraid for so long when the brain’s first alarm fires so fast

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Why do we stay afraid for so long when the brain's first alarm fires so fast?

September 18, 2026

September 18, 2026

• Highlights
• Salk neuroscientists identify and characterize new region in the brain's fear circuit called the amygdalostriatal transition zone (ASt)
• ASt neurons fire with more strength and for longer than the amygdala, which has historically been considered the brain's fear center
• Findings explain why fear responses like freezing can last so long and point to therapeutic innovations for disorders like PTSD, anxiety

LA JOLLA-Our survival depends on brains that constantly search for danger and, if found, stay alert until it has passed. The amygdala-an area that sits deep in the brain, near the brain stem-has long been considered the epicenter of our fear and danger response. But the amygdala's neurons fire only briefly when a threat first appears, so why do fear-response behaviors like fight, flight, or freeze last so long?

Salk Institute neuroscientists turned to a mouse model to find an answer: an overlooked brain region that sits next to the amygdala, called the amygdalostriatal transition zone (ASt). Unlike the amygdala's neurons, neurons in the ASt fire with both strength and longevity-explaining why some defensive responses persist. The insights into the brain's fear circuitry may be used in future therapeutic development for fear and panic disorders.

The study, published in Neuron on September 14, 2026, was funded by private philanthropy and federal grants from the National Institutes of Health.

What is the amygdalostriatal transition zone?

Kay Tye's lab identified the brain region, the amygdalostriatal transition zone (ASt), responsible for danger responses lasting long amounts of time. From left: Christian Cazares, Faith Aloboudi, May Chan, Christopher Lee, Felix Taschbach, Fergil Mills, Kay Tye, Romy Wichmann, Nikki Keisler, Gates Schneider, Laurel Keyes.
Click here for the original image.
Credit: Salk Institute

"People always thought the amygdala was the fear center, while ignoring the space between the basolateral and central amygdala entirely," says co-corresponding author Kay Tye, PhD, a professor and holder of the Wylie Vale Chair at Salk and Howard Hughes Medical Institute investigator. "In the amygdala, you have firing right at the beginning of the danger-but what about after that? What is causing that lingering fear? What if it's the amygdalostriatal transition zone?"

The ASt is tiny-it's hard to reach, hard to study, and hard to distinguish from surrounding brain regions. Because of these challenges, the ASt has been relatively unexplored, leaving scientists unsure whether it is even a distinct brain region. This is the first landmark in the Salk paper: The researchers show that the mouse ASt is a distinct brain region, separate from the neighboring amygdala and striatum regions.

"The ASt is at a crossroads between the brain's systems for emotional associations and action selection, but its function was largely unknown," says co-corresponding author Fergil Mills, PhD, a former postdoctoral researcher in Tye's lab and current assistant professor at the University of Utah.

How is the amygdalostriatal transition zone involved in fear?

After determining the ASt is distinct, the researchers moved on to characterizing its involvement in the danger response. Electrophysiology and calcium imaging revealed that the ASt's neurons have a robust, sustained response to danger cues.

To further explore the effect ASt neurons have on danger response behaviors, the Salk team also specifically stimulated and inhibited only the ASt's neurons. Stimulation of the ASt drove freezing and avoidance behaviors; inhibition of the ASt revealed that a specific subset of dopamine-expressing neurons in the region is necessary to mount fear responses.

What do these findings mean for fear and panic disorders?

"This project has been an amazing adventure. When we started, we knew almost nothing about the ASt, and were truly exploring unknown territory in the brain," says Mills. "Now, we have a much deeper understanding of this structure and have found that the ASt is a 'missing piece' of the circuits for fear that was hiding in plain sight for decades."

"The ASt and this circuit could be really relevant in developing therapies for panic attacks or phobias," adds Tye. "Anxiety disorders affect hundreds of millions of people globally. Understanding what happens in the brain when it's in high-alert danger mode is key to addressing those disorders."

Further research is needed to explore the new fear circuit now that it includes the ASt. The findings offer promising insights in the ongoing effort to create more effective, targeted therapeutics for conditions like post-traumatic stress disorder (PTSD), panic disorder, and anxiety.

Other authors and funding

This paper was co-first authored by Christopher Lee of Salk, UC San Diego, and Howard Hughes Medical Institute, James Howe of UC San Diego, and Hao Li of Salk. Other authors include Maria Keisler of UC San Diego and Howard Hughes Medical Institute; Shan Shao of Peking University; Felix Taschbach and Kanha Batra of Salk and UC San Diego; Mackenzie Lemieux, Matilde Borio, Reesha Patel, Meenakshi Asokan, Christian Cazares, Liezl Maree, and Talmo Pereira of Salk; Faith Aloboudi, Jesse White, May Chan, Laurel Keyes, Gates Schneider, Jeremy Delahanty, and Romy Wichmann of Salk and Howard Hughes Medical Institute; Hannah Chen of MIT; Fabiha Bushra, Dani Lemmon, Kyung Lee, Christopher Heyman, and Nicholas Poll of University of Utah; Alexa Gross of Wellesley College; and Marcus Benna and Cory Root of UC San Diego.

This study was funded by the National Institutes of Health (P30 CA014195, P30 AG068635, S10-MH124757, R01-MH115920, R37-MH102441, DP1-AT009925, K99 MH121563, K99 DA055111-01, K99 AA029180, K00 MH132569), Henry L. Guenther Foundation, Waitt Foundation, JPB Foundation, New York Stem Cell Foundation, Klingenstein Foundation, McKnight Foundation, Howard Hughes Medical Institute, Clayton Foundation, Kavli Foundation, Dolby Family Fund, Canadian Institutes of Health Research, Duke University, and China Scholarship Council.

This press release was written by Isabella Davis
Contact: [email protected]

DOI: 10.1016/j.neuron.2026.08.012