Inhibitory neurons marked by the connectivity molecule Kirrel3 regulate memory precision.

ABSTRACT: The homophilic adhesion molecule Kirrel3 drives synapse formation between dentate granule (DG) neurons and GABA neurons, and Kirrel3 gene variants are associated with neurodevelopmental disorders in humans. However, the circuit function and behavioral relevance of Kirrel3-expressing neurons are unknown. Using intersectional genetics, we identified a population of Kirrel3-expressing GABA neurons that regulate memory discrimination in male and female mice. Using chemogenetics with in vivo electrophysiology and behavioral assays, we discovered that activating Kirrel3-expressing GABA neurons, but not parvalbumin neurons, potently inhibits CA3 neuron activity and impairs contextual memory discrimination during recall, revealing a critical role for these neurons in the retrieval of precise memor

SUBMITTER: Tunon-Ortiz A 

PROVIDER: S-EPMC11245094 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature