The region in question is called the amygdalostriatal transition zone, abbreviated ASt, and it sits at the boundary between the amygdala and the striatum, wedged between the basolateral and central subdivisions of the amygdala. According to the new study, published in the journal Neuron on September 14, 2026, ASt neurons behave in a way that the amygdala’s neurons do not: they fire with both greater strength and greater longevity in response to danger cues. Where the amygdala sounds a brief first alarm, the ASt appears to sustain the signal, providing the neural substrate that keeps defensive behaviors running after the initial detection of threat has passed. In other words, the ASt may be the missing piece that explains the temporal gap between the brain’s rapid detection of danger and the prolonged behavioral response that follows it.

The path to this discovery was far from straightforward. The ASt is a difficult target for neuroscientists. It is tiny, it is hard to reach with recording and manipulation tools, and it is hard to distinguish anatomically from the larger, better-studied regions that surround it. Because of these technical challenges, the area had been largely ignored, and researchers were not even certain whether it qualified as a distinct brain region at all. Many simply treated it as an unremarkable transition between the amygdala and the striatum, a boundary zone with no special identity or function of its own. The Salk team’s first landmark achievement was to demonstrate that the mouse ASt is in fact a distinct brain region, separate from both the neighboring amygdala and the striatum, with its own definable boundaries and characteristics.

Co-corresponding author Kay Tye, a professor at Salk and holder of the Wylie Vale Chair, as well as a Howard Hughes Medical Institute investigator, described how the field’s long-standing focus on the amygdala had blinded researchers to what lay between its subdivisions. People always thought the amygdala was the fear center while ignoring the space between the basolateral and central amygdala entirely, she noted. In the amygdala, firing occurs right at the beginning of the danger, but that raised the question of what happens afterward, what causes the lingering fear, and whether the amygdalostriatal transition zone might be responsible. Her lab’s work suggests that the answer to that question is yes, and that the sustained firing properties of ASt neurons are precisely what bridge the gap between brief detection and prolonged defense.

Co-corresponding author Fergil Mills, a former postdoctoral researcher in Tye’s lab who is now an assistant professor at the University of Utah, emphasized the region’s strategic position in the brain’s architecture. The ASt sits at a crossroads between the brain’s systems for emotional associations and action selection, he explained, yet its function had remained largely unknown until now. That anatomical position is significant. Emotional associations, encoded in circuits like the amygdala, tell an animal what to fear, while action selection systems, including the striatum, determine what the animal does about it. A region positioned between the two, capable of sustained activity, is ideally placed to translate a fleeting emotional signal into a persistent behavioral program such as freezing or avoidance.

To characterize the ASt’s role in the danger response, the researchers combined electrophysiology with calcium imaging, two complementary techniques for monitoring neural activity. Electrophysiology records the electrical impulses of individual neurons with millisecond precision, while calcium imaging tracks activity across populations of cells over longer periods. Together, these methods revealed that ASt neurons mount a robust and sustained response to danger cues, in marked contrast to the brief firing pattern observed in the amygdala. This sustained activity profile provides a mechanistic explanation for why defensive behaviors like freezing can persist long after the initial threat signal has been detected, resolving a question that the amygdala-centric view of fear could not answer.

The team then went beyond observation to test causation, using targeted stimulation and inhibition of ASt neurons in a mouse model. When the researchers stimulated the ASt, the animals exhibited freezing and avoidance behaviors, the classic defensive responses to perceived danger. When they inhibited the region, the experiments revealed something more specific: a particular subset of dopamine-expressing neurons within the ASt is necessary for the animal to mount fear responses at all. The involvement of dopamine in this context is notable, since the neurotransmitter is more commonly associated with reward and motivation, and its role in a sustained fear circuit underscores how intertwined the brain’s emotional and motivational systems really are.

Mills reflected on the journey from ignorance to insight that the project represented. When the team started, he said, they knew almost nothing about the ASt and were truly exploring unknown territory in the brain. Now, he added, they have a much deeper understanding of the structure and have found that the ASt is a missing piece of the fear circuits that was hiding in plain sight for decades. That framing captures the significance of the work for basic neuroscience. The canonical fear circuit, built around the amygdala’s detection of threat and its outputs to downstream defensive systems, now has an additional node, one whose sustained firing properties may be essential to the temporal dynamics of fear itself.

The clinical implications could be substantial. Tye pointed out that the ASt and its circuit could be highly relevant to developing therapies for panic attacks or phobias, noting that anxiety disorders affect hundreds of millions of people globally and that understanding what happens in the brain during high-alert danger mode is key to addressing those conditions. Conditions such as post-traumatic stress disorder, panic disorder, and generalized anxiety are all characterized by fear responses that are excessive, prolonged, or triggered inappropriately. If sustained ASt activity is what keeps defensive behaviors running, then the region and its dopamine-expressing neurons represent a potential therapeutic target, one that could allow more precise interventions than broad approaches aimed at the amygdala as a whole.

The study was funded by private philanthropy and federal grants from the National Institutes of Health, and it involved a large collaborative team. Co-first authors include Christopher Lee of Salk, UC San Diego, and the Howard Hughes Medical Institute, James Howe of UC San Diego, and Hao Li of Salk, with additional contributors from institutions including Peking University, MIT, Wellesley College, the University of Utah, and UC San Diego. The researchers stress that further work is needed to explore the newly expanded fear circuit now that it includes the ASt, mapping its connections, its role in different types of threat, and its behavior in disease states. But the core message of the study is already clear: the brain’s fear system is more elaborate than the textbook version suggests, and the persistence of fear, the quality that makes it so clinically troublesome, may depend not on the alarm itself but on a small transition zone that kept the signal going all along.

Subject of Research: The role of the amygdalostriatal transition zone in sustaining fear and defensive behaviors in the mouse brain

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

Article References: Why do we stay afraid for so long when the brain’s first alarm fires so fast?. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: amygdalostriatal transition zone, amygdala, fear circuitry, neuroscience, dopamine neurons, freezing behavior, PTSD, panic disorder, anxiety, electrophysiology, calcium imaging, Salk Institute