HIPPOCAMPAL CIRCUIT RESEARCH
Non-canonical connections between the subiculum complex and hippocampal CA1
We developed and applied a Cre-dependent, genetically modified rabies-based tracing system to map direct synaptic connections to specific CA1 neuron types in the mouse hippocampus (Sun et al., 2014). We found common inputs to excitatory and inhibitory CA1 neurons from CA3, CA2, the entorhinal cortex (EC), the medial septum (MS), and, unexpectedly, the subiculum. Excitatory CA1 neurons receive inputs from both cholinergic and GABAergic MS neurons, whereas inhibitory neurons receive a great majority of inputs from GABAergic MS neurons. Both cell types also receive weaker input from glutamatergic MS neurons. Comparisons of inputs to CA1 PV+ interneurons versus SOM+ interneurons showed similar strengths of input from the subiculum, but PV+ interneurons received much stronger input than SOM+ neurons from CA3, the EC, and the MS. Thus, rabies tracing identifies hippocampal circuit connections and maps how the different input sources to CA1 are distributed with different strengths on each of its constituent cell types.
A Novel Cortico-Hippocampal Pathway Facilitates Object-Place Learning
Recently we show that the afferent circuitry of CA1-projecting subicular neurons is biased by inputs from CA1 inhibitory neurons as well as visual cortex, but lacks input from entorhinal cortex. Efferents of the CA1-projecting subiculum neurons also target 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 as well as their responses to displaced objects. Together, these experiments reveal a novel pathway by which cortical inputs, particularly those from visual cortex, reach hippocampal output region CA1, and our findings implicate this circuitry in the formation of complex spatial representations and learning of object-place associations.
Relevant References:
Sun, Y., Nguyen, A., Nguyen, J., Le, L., Saur, D., Choi, J., Callaway, E.M., Xu, X. (2014) Cell-type specific circuit connectivity of hippocampal CA1 revealed through Cre-dependent rabies tracing. Cell Reports Cell Rep. 2014 Apr 10;7(1):269-80. doi: 10.1016/j.celrep.2014.02.030. Epub 2014 Mar 20.
Xu X, Sun Y, Holmes, TC, López A. Non-canonical connections between the subiculum and hippocampal CA1. J Comp Neurol. 2016, 524:3666-3673 [PMID: 27150503]
Sun, Y., Nitz, D.A., Holmes, T.C., Xu, X. (2018) Opposing and complementary topographic connectivity gradients revealed by quantitative analysis of canonical and non-canonical hippocampal CA1 inputs. eNeuro DOI: https://doi.org/10.1523/ENEURO.0322-17.2018
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 # (2019) CA1-projecting Subirulum Neurons Facilitate Object-Place Learning. Nature Neuroscience https://rdcu.be/bRIhc