Ventral and Intermediate Hippocampus Are Required for Object-in-Place Recognition Memory in Mice

Many behaviors that are essential for survival, such as retrieving food, finding shelter, and locating predator cues, rely on forming effective associations between the identity and location of spatial elements. This identity-location association is commonly assessed in rodents using spontaneous object-in-place (OiP) recognition memory tasks. OiP recognition memory deficits are seen in autism spectrum disorder and schizophrenia and are used to detect early onset of Alzheimer's disease. These deficits are replicated in animal models of neurodevelopmental, neurodegenerative, and chromosomal disorders. The ventral hippocampus (HPC) has been implicated in object recognition, but its contribution to OiP memory has not been established. Despite the broad adoption of mouse models in behavioral and systems neuroscience research for their ease of genetic manipulations, the neural correlates of OiP memory in mice remain unknown. Here we used chemogenetics to assess the contribution of the ventral and intermediate CA1 (vCA1 and iCA1, respectively) subregions of the HPC, as well as the medial prefrontal cortex (mPFC) and iCA1-mPFC projections to OiP memory in male and female C57BL/6J mice. We found that two-object OiP requires the activity of the vCA1 and iCA1, but not the mPFC or iCA1-mPFC connections. Our data identify a requirement for two hippocampal subregions in the successful assessment of OiP recognition memory in mice, expanding our understanding of the neural basis of spatial memory processing.