A team of scientists discovered how newly identified neural circuits in the brain's hippocampal formation play a critical role in object-location learning and memory. The study was published in Nature Neuroscience.

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.

Authors how 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.

They 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, the experiments reveal a novel pathway by which cortical inputs, particularly those from the visual cortex, reach the hippocampal output region CA1.

"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 the senior author.

The researchers 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.

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.

https://www.nature.com/articles/s41593-019-0496-y