Critical role of brain circuits in improving learning and memory revealed

Summary: A newly identified neural network in the hippocampal formation plays a critical role in memory and object-location learning. The findings are highly relevant to learning and memory disorders, including Alzheimer’s disease.

Source: UC Irvine

A University of California, Irvine-led team of scientists has discovered how newly identified neural circuits in the brain’s hippocampal formation play a critical role in object-location learning and memory.

The study, published today in Nature Neuroscience, was led by Xiangmin Xu, PhD, an anatomy and neurobiology professor in the UCI School of Medicine, and conducted in collaboration with Douglas A. Nitz, PhD, professor and chair of the Department of Cognitive Science at the University of California, San Diego; Qing Nie, PhD, Chancellor’s Professor of mathematics and developmental and cell biology at UCI; and, Todd C. Holmes, professor and vice chair of UCI’s Department of Physiology & Biophysics.

Loss of object location memory is one of the key impairments in Alzheimer’s disease (AD), the most common form of dementia in the elderly. These new findings in hippocampal circuit mechanisms provide an intriguing new target to counteract AD-related memory impairments.

“Our study was made possible by new viral genetic based mapping approaches for examining connectivity between structures. These new mapping tools enabled us to identify novel circuits within and between the hippocampus and cortex,” said Xu.

Xu and his colleagues used monosynaptic rabies retrograde tracing and herpes (H129)-based anterograde tracing to establish new cortico-hippocampal circuitry associated with subiculum (SUB) projections to hippocampal CA1. Xu and an international team of investigators was recently awarded an NIH BRAIN Initiative grant to develop new H129 viral tracers as a brain mapping tool for use by the entire neuroscience community.

This shows a swirly brain
These new findings in hippocampal circuit mechanisms provide an intriguing new target to counteract AD-related memory impairments. The image is in the public domain.

The team revealed the hippocampal sub-circuit mechanism highly relevant to learning and memory disorders including Alzheimer’s disease. These findings may be used to better treat Alzheimer’s disease and other neurological disorders, delay their onset, and possibly prevent them from developing in the first place.

Funding: This study was supported by the National Institutes of Health, including a BRAIN Initiative grant and other grants, the National Science Foundation, and the Simons Foundation.

About this neuroscience research article

UC Irvine
Media Contacts:
Anne Warde – UC Irvine
Image Source:
The image is in the public domain.

Original Research: Closed access
“CA1-projecting subiculum neurons facilitate object–place learning”. Yanjun Sun, Suoqin Jin, Xiaoxiao Lin, Lujia Chen, Xin Qiao, Li Jiang, Pengcheng Zhou, Kevin G. Johnston, Peyman Golshani, Qing Nie, Todd C. Holmes, Douglas A. Nitz & Xiangmin Xu.
Nature Neuroscience doi:10.1038/s41593-019-0496-y.


CA1-projecting subiculum neurons facilitate object–place learning

Recent anatomical evidence suggests a functionally significant back-projection pathway from the subiculum to the CA1. Here we show that the afferent circuitry of CA1-projecting subicular neurons is biased by inputs from CA1 inhibitory neurons and the visual cortex, but lacks input from the entorhinal cortex. Efferents of the CA1-projecting subiculum neurons also target the perirhinal cortex, an area strongly implicated in object–place learning. We identify a critical role for CA1-projecting subicular neurons in object-location learning and memory, and show that this projection modulates place-specific activity of CA1 neurons and their responses to displaced objects. Together, these experiments reveal a novel pathway by which cortical inputs, particularly those from the visual cortex, reach the hippocampal output region CA1. Our findings also implicate this circuitry in the formation of complex spatial representations and learning of object–place associations.

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