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

Abstract

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.

Prefrontal Nectin3 Reduction Mediates Adolescent Stress-Induced Deficits of Social Memory, Spatial Working Memory, and Dendritic Structure in Mice

“…warranted to investigate the effects of adolescent chronic stress on other stress-related regions and mPFC-related circuits [27,53]. Structural plasticity was also altered differently by nectin3 knockdown and adolescent stress: while nectin3 knockdown caused a specific loss of thin spines, adolescent stress affected multiple spine types.…”

“…One explanation for these differences may be that the regions affected in nectin3 knockdown and adolescent stress were different: while nectin3 knockdown was confined to the PFC, adolescent stress experiences may affect multiple stress-related regions such as the hippocampus [ 27 ], which may underlie the increased anxiety-like behaviors induced by chronic stress. As our study primarily focused on the mPFC, future studies are warranted to investigate the effects of adolescent chronic stress on other stress-related regions and mPFC-related circuits [ 27 , 53 ]. Structural plasticity was also altered differently by nectin3 knockdown and adolescent stress: while nectin3 knockdown caused a specific loss of thin spines, adolescent stress affected multiple spine types.…”

Activation of ventrolateral orbital cortex improves mouse neuropathic pain–induced anxiodepression

“…A number of studies showed that neuropathic pain–induced mood disorders are sensitive to treatments with anxiolytics and antidepressants ( 9 , 10 ). Functional imaging studies in humans and animal models of chronic pain reveal structural changes in the corticolimbic brain areas, including anterior cingulate cortex (ACC), medial prefrontal cortex (mPFC), amygdala, hippocampus, and orbitofrontal cortex (OFC), which support emotion, behavior, motivation, and memory functions ( 11 , 12 ). As a major subdivision of the PFC, the OFC participates directly in negative emotional processing ( 13 – 16 ).…”

A Conditioning-Strengthened Circuit From CA1 of Dorsal Hippocampus to Basolateral Amygdala Participates in Morphine-Withdrawal Memory Retrieval

“…We further studied what brain regions connect the CA1 of dorsal hippocampus to the BLA during conditioned context-induced retrieval of morphine withdrawal memory. The POR is bordered by the following structures: the caudal end of the angular bundle, the caudal part of the perirhinal cortex, the ventral temporal association area, and the dorsal part of the medial entorhinal cortex ( Qi et al, 2019 ). The POR receives direct projections from the CA1 of dorsal hippocampus ( Furtak et al, 2007 ; Agster and Burwell, 2013 ) and sends projections onto a number of cortical and subcortical areas ( Delatour and Witter, 2002 ; Agster and Burwell, 2009 ).…”