Science1 publisher2 min readPublished
Salk pins lingering fear in mice on a zone between the amygdala and striatum
Salk researchers recorded and then manipulated the amygdalostriatal transition zone in freely moving mice, and report in Neuron that dopamine-expressing neurons there are needed to mount a fear response.
The Scientist · Science desk
What happened
- In recordings from freely moving mice, amygdala activity fell away soon after a threat appeared while neurons in the neighbouring amygdalostriatal transition zone kept firing for as long as the threat lasted.
- Activating those neurons directly produced freezing and active avoidance, which the Salk release describes as mirroring the high-alert defensive states mice show under threat.
- Silencing the region blunted defensive responses, and a distinct population of dopamine-expressing neurons inside it proved necessary for the mice to mount a fear response.
- The team also concluded that the mouse zone is its own anatomical and functional structure, separate from the amygdala beside it and from the striatum it borders.
- The recordings combined cellular-resolution calcium imaging with in vivo electrophysiology in mice that were free to move while danger cues were presented.
Compiled by The ScientistSomething wrong?How this is made
Why it matters
- capability A named cell type inside a defined region is something an experiment can switch off on its own, without quieting the whole amygdala and dragging every other amygdala function along with it.
- constraint The small footprint and deep position that kept this zone off the map also limit how precisely anyone can target or image it, and in a larger brain that thin transition zone is just as hard to hit.
- decision Labs that have recorded across the basolateral-to-central amygdala border now have to decide whether their electrodes were sampling one region or two, and whether old datasets need re-scoring.
The puzzle that set this up is one of timing. Amygdala neurons fire mostly in a brief burst when a danger cue first appears [1], and a brief burst is a thin explanation for an animal that stays defensive while the threat is still there. Kay Tye, who holds the Wylie Vale Chair at Salk and is a co-corresponding author on the paper [15], put the gap this way in the institute's release: "In the amygdala, you have firing right at the beginning of the danger, but what about after that? What is causing that lingering fear?" [11]
The region had been skipped for practical reasons. It is small and deep, and until now researchers were not sure whether it was a genuine structure or just an ambiguous border between the basolateral and central amygdala [13]. It sits where the brain's emotional associations meet the striatum's job of choosing actions [14]. "The ASt is at a crossroads between the brain's systems for emotional associations and action selection, but its function was largely unknown," said Fergil Mills, the other co-corresponding author, now an assistant professor at the University of Utah [12][16].
Sufficiency and necessity do different jobs here, and the paper runs both. Driving the neurons and getting freezing [7] shows the zone can produce a defensive state; it does not show that the sustained firing seen during a natural threat is what holds that state up. The silencing arm is the one that speaks to that, and it is the more portable result, because it lands on a dopamine-expressing cell population [9]. Optogenetic and chemogenetic manipulations were both used [10].
Neurosciencenews.com headlined the work "Missing Brain Circuit Behind Chronic Fear Identified" [19]. What the release describes is sustained activity across threat cues [2], which is a different measurement from fear that outlives the threat. Anxiety and post-traumatic states are the second case. Testing that would mean watching the same neurons after the cue stops, in an animal whose danger has passed, and the release does not describe such an experiment.
Silencing "attenuated" defensive responses, in the release's own word [8]. By how much, the release does not say. It reports no quantitative values at all, no mouse count, no firing rate, no effect size [18].
What to watch
- The Neuron paper itself, for mouse counts, firing rates, and whether amygdala and ASt activity were recorded in the same animals.
- Whether the dopamine-expressing ASt neurons can be reached by anything other than a virus delivered into the region.
- Whether an equivalent transition zone can be identified in primate or human brains, given the size that kept it off the mouse map.