Fibronectin1‐Expressing Subicular Circuits Selectively Govern the Retrieval of Novel Object Recognition

Novel object recognition (NOR), referring to the cognitive ability to differentiate familiar/novel objects, is a fundamental cognitive function essential for daily life. However, the mechanisms underlying the encoding of novel preference information remain incompletely understood. Here, we demonstrate that the fibronectin1-expressing subiculum-entorhinal circuits selectively govern NOR retrieval. Subicular pyramidal neurons are able to differentiate between familiar and novel objects, and bidirectionally regulate the retrieval of NOR. At the circuit level, subicular-entorhinal projections, rather than those targeting the anterior nucleus of thalamus, mammillary bodies or retrosplenial cortex, encode novel object preference and regulate NOR retrieval. Importantly, fibronectin1 is identified as a key functional molecular component expressing within this glutamatergic circuit, gates neuronal excitability by regulating the large conductance Ca2+-activated potassium channel, and selectively governs the NOR retrieval. These findings provide novel insights into the molecular and circuit-level mechanisms of NOR and highlight potential therapeutic targets for cognitive disorders targeting fibronectin1-expressing subicular circuits.