Abstract: Spatial memory is crucial for survival within external surroundings and wild environments. The hippocampus, a critical hub for spatial learning and memory formation, has received extensive investigations on how neuromodulators shape its functions (Teixeira et al., 2018; Zhang et al., 2024). However, the landscape of neuromodulations in the hippocampal system remains poorly understood because most studies focus on classical monoamine neuromodulators, such as acetylcholine, serotonin, dopamine, and noradrenaline. The neuropeptides, comprising the most abundant neuromodulators in the central nervous system, play a pivotal role in neural information processing in the hippocampal system. Cholecystokinin (CCK), one of the most abundant neuropeptides, has been implicated in regulating various physiological and neurobiological statuses (Chen et al., 2019). CCK-A receptor (CCK-AR) and CCK-B receptors (CCK-BR) are two key receptors mediating the biological functions of CCK, both of which belong to class-A sevenfold transmembrane G protein-coupled receptors (Nishimura et al., 2015). CCK-AR preferentially reacts to sulfated CCK, whereas CCK-BR binds both CCK and gastrin with similar affinities (Ding et al., 2022). The expression patterns of CCK-AR and CCK-BR are distinct, implying that CCK has various functions in target regions. For instance, CCK-AR is widely expressed in the GI and brain subregions and is hence implicated in the control of digestive function and satiety regulation. Conversely, CCKBR is abundantly and widely distributed in the central nervous system, which majorly regulates anxiety, learning, and memory (Ding et al., 2022). However, the roles of endogenous CCK and CCK receptors in regulating hippocampal function at electrophysiological and behavioral levels have received less attention.