The Glutamatergic Postrhinal Cortex–Ventrolateral Orbitofrontal Cortex Pathway Regulates Spatial Memory Retrieval

Xinyang Qi1 • Zhanhong Jeff Du2 • Lin Zhu1 • Xuemei Liu2 • Hua Xu1 • Zheng Zhou2 • Cheng Zhong2 • Shijiang Li3 • Liping Wang2,* • Zhijun Zhang1,2,*
1Department of Neurology, Affiliated ZhongDa Hospital, Institute of Neuropsychiatry, School of Medicine, Southeast University, Nanjing 210009, China
2Shenzhen Key Lab of Neuropsychiatric Modulation and Collaborative Innovation Center for Brain Science, Chinese Academy of Sciences (CAS) Center for Excellence in Brain Science and Intelligence Technology, the Brain Cognition and Brain Disease Institute for Collaboration Research of the Shenzhen Institutes of Advanced Technology at the CAS and the McGovern Institute at Massachusetts Institute of Technology, Shenzhen 518055, China
3Department of Biophysics, Medical College of Wisconsin, Milwaukee, WI 53226, USA


A deficit in spatial memory has been taken as an early predictor of Alzheimer’s disease (AD) or mild cognitive impairment (MCI). The uncinate fasciculus (UF) is a long-range white-matter tract that connects the anterior temporal lobe with the orbitofrontal cortex (OFC) in primates. Previous studies have shown that the UF impairment associated with spatial memory deficits may be an important pathological change in aging and AD, but its exact role in spatial memory is not well understood. The pathway arising from the postrhinal cortex (POR) and projecting to the ventrolateral orbitofrontal cortex (vlOFC) performs most of the functions of the UF in rodents. Although the literature suggests an association between spatial memory and the regions connected by the POR–vlOFC pathway, the function of the pathway in spatial memory is relatively unknown. To further illuminate the function of the UF in spatial memory, we dissected the POR–vlOFC pathway in mice. We determined that the POR–vlOFC pathway is a glutamatergic structure, and that glutamatergic neurons in the POR regulate spatial memory retrieval. We also demonstrated that the POR–vlOFC pathway specifically transmits spatial information to participate in memory retrieval. These findings provide a deeper understanding of UF function and dysfunction related to disorders of memory, as in MCI and AD.


Spatial memory; Postrhinal cortex; Ventrolateral orbitofrontal cortex; Mild cognitive impairment; Alzheimer’s disease


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