A team at Spain’s Institute for Neurosciences reports that restoring the excitability balance of basolateral amygdala neurons reversed anxiety- and social-deficit behaviors in mice, according to an iScience study published May 13, 2025.
Researchers at the Institute for Neurosciences (CSIC–UMH) in Alicante, Spain, report that correcting hyperexcitability in a defined amygdala circuit reverses anxiety-like and social behaviors in mice. The peer‑reviewed paper appeared in iScience on May 13, 2025 (eCollection June 20). ScienceDaily later summarized the findings on November 4, 2025. (pubmed.ncbi.nlm.nih.gov)
In the study, first author Álvaro García and colleagues used a mouse line with increased copies of Grik4, which elevates GluK4-type kainate receptors and disrupts amygdala output. Using stereotaxic AAV–Cre to normalize Grik4 specifically in basolateral amygdala pyramidal neurons, the team restored synaptic strength onto “regular‑firing” neurons in the centrolateral amygdala—a population the authors implicate as central to affective behaviors. (pubmed.ncbi.nlm.nih.gov)
Behaviorally, normalizing Grik4 dosage abolished anxiety-, depression-, and social‑interaction deficits in the transgenic mice, while object‑recognition memory impairments persisted—pointing to roles for additional regions such as the hippocampus. Assays included open‑field and elevated‑plus maze tests, forced‑swim, and social‑interaction paradigms; electrophysiology confirmed circuit changes. (pubmed.ncbi.nlm.nih.gov)
Beyond the engineered line, the team also reports reduced anxiety after applying the same basolateral‑amygdala targeting strategy to wild‑type mice that naturally exhibited higher anxiety levels, according to institutional materials distributed via ScienceDaily, the CSIC website, and EurekAlert. (This specific wild‑type extension is described in those releases rather than in the PubMed abstract.) (sciencedaily.com)
“We’ve identified a specific population of neurons whose imbalanced activity alone is sufficient to trigger pathological behaviors,” said senior author Juan Lerma, while García noted that “that simple adjustment was enough to reverse anxiety‑related and social‑deficit behaviors.” These quotations were provided in the university’s news materials. (sciencedaily.com)
The authors situate the work within a program that began with the lab’s Grik4‑overexpression model first reported in 2015, and a subsequent 2018 study showing circuit‑level imbalances—both precursors to the current circuit‑correction approach. (pmc.ncbi.nlm.nih.gov)
Funding came from Spain’s State Research Agency (AEI), the Severo Ochoa Excellence Program at the Institute for Neurosciences (CSIC‑UMH), the European Regional Development Fund, and the Generalitat Valenciana’s PROMETEO and CIPROM programs. (sciencedaily.com)