2023-10-16 15:25作者：心靈健身房
The hippocampal formation is a key brain region that plays an important role in spatial navigation, learning and memory. While the canonical hippocampal circuits such as the trisynaptic circuits have been well established, modern neural circuit mapping tools have allowed for important discoveries of new pathways within this brain region. Such pathways as illustrated in the figure insert, including the mossy fiber pathway (dentate gyrus -> CA3), Schaffer collateral pathway (CA3 -> CA1) and CA1 -> subiculum feedforward pathway are known to play essential roles in learning and memory behaviors. Apart from these canonical pathways, accumulating anatomical and physiological evidence indicates that some important aspects of the hippocampal circuits remain to be further understood. Thus many researchers wonder if the hippocampal region still has some new pathways, and if so, what function they have. Prof. Xu Xiangmin from the University of California, Irvine (UCI) addressed these relevant questions in his talk.
Santiago Ramón y Cajal (1911)
Prof. Xu and his colleagues have used new viral-genetic mapping tools including monosynaptic rabies retrograde tracing and herpes (H129)-based anterograde tracing to establish new cortico-hippocampal circuitry associated with subiculum (SUB) projections to CA1. Specifically, monosynaptic rabies tracing identifies a significant SUB-CA1 back-projection pathway in mice, suggested previously in other mammalian species using less strict mapping methods. Then they identified a distinct sub-population of SUB neurons forming a pathway from visual cortex to CA1 and perirhinal cortex. Selective labeling of CA1-projecting excitatory SUB neurons is achieved by canine adenovirus 2 (CAV2)-mediated retrograde Cre expression. The output projections of CA1-projecting SUB neurons are mapped using Cre-dependent anterograde directed herpes simplex virus (H129 strain). Complementing the unique efferent circuitry of SUB neurons projecting to CA1, they observed that these cell types are also unique in the composition of their afferents. The direct path from visual cortex to CA1-projecting SUB neurons and their output to CA1 and perirhinal cortex strongly suggest that one role for this circuitry may be to provide critical information necessary for conjunctive object-place representations in hippocampus and perirhinal cortices.
Xiangmin Xu, Ph.D.
To test this, they used DREADDs (designer receptors exclusively activated by designer drugs) mediated inactivation of CA1-projecting excitatory SUB neurons to determine whether they are necessary for object-location learning behavior. They also asked whether stimulation of SUB inputs to CA1 and perirhinal cortex could enhance object-location memory. It turns out that activation and inactivation of these neurons promotes and suppresses, respectively, formation of object-location memories.
Together we learn that there is a non-canonical back-projection pathway from CA1 to subiculum, and that the larger cortico-hippocampal circuitry associated with this pathway plays a critical role in object-place learning. This identified hippocampal sub-circuit mechanism is highly relevant to learning and memory disorders including Alzheimer's disease. Prof. Xu’s findings may be used to better treat this and other diseases, delay their onset, and prevent them from developing.
