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

ABSTRACT 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 Ca 2+ ‐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.