Cell-Type Specific Circuits in the Mammillary Body for Place and Object Recognition Memory

Mammillary body (MB) is traditionally viewed as a structural node of an anatomic circuit for emotion and memory. However, little is known about its molecular and cellular organizations. Here, a discovery that MB contains four subtypes of neurons that occupy different spatial subregions is reported. Of these, two subtypes of neurons are tagged by parvalbumin (PV) and dopamine receptor-D2 (Drd2) markers. PV neurons are spontaneously active, whereas Drd2 neurons are inactive at rest and generate rebound bursts. These two distinct electrophysiological properties are encoded by Kcnn4 and Cacna1h. PV and Drd2 neurons generate two distinct cell-type specific circuits by receiving inputs from two discrete subiculum neuronal classes. Gain- and loss-of-function studies on these cortical-subcortical circuits demonstrate their differential roles for place and object recognition memory. This finding provides a comprehensive molecular and structural atlas of MB neurons at single-cell resolution and reveals that MB contains molecularly, structurally, and functionally dissociable streams within its serial architecture.