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eNeuro. 2018 Jan 30;5(1). pii: ENEURO.0322-17.2018. doi: 10.1523/ENEURO.0322-17.2018. eCollection 2018 Jan-Feb.

Opposing and Complementary Topographic Connectivity Gradients Revealed by Quantitative Analysis of Canonical and Noncanonical Hippocampal CA1 Inputs.

Sun Y1, Nitz DA2, Holmes TC3, Xu X1,4,5,6.

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Department of Anatomy and Neurobiology, School of Medicine, University of California, Irvine, CA 92697-1275.
Department of Cognitive Science, University of California, San Diego, La Jolla, CA 92093.
Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, CA 92697-4560.
Department of Biomedical Engineering, University of California, Irvine, CA 92697-2715.
Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine, CA 92697-4025.
Department of Computer Science, University of California, Irvine, CA 92697-3435.


Physiological studies suggest spatial representation gradients along the CA1 proximodistal axis. To determine the underlying anatomical basis, we quantitatively mapped canonical and noncanonical inputs to excitatory neurons in dorsal hippocampal CA1 along the proximal-distal axis in mice of both sexes using monosynaptic rabies tracing. Our quantitative analyses show comparable strength of subiculum complex and entorhinal cortex (EC) inputs to CA1, significant inputs from presubiculum and parasubiculum to CA1, and a threefold stronger input to proximal versus distal CA1 from CA3. Noncanonical subicular complex inputs exhibit opposing topographic connectivity gradients whereby the subiculum-CA1 input strength systematically increases but the presubiculum-CA1 input strength decreases along the proximal-distal axis. The subiculum input strength cotracks that of the lateral EC, known to be less spatially selective than the medial EC. The functional significance of this organization is verified physiologically for subiculum-to-CA1 inputs. These results reveal a novel anatomical framework by which to determine the circuit bases for CA1 representations.


Circuit connections; hippocampus; imaging; quantitative; viral tracing

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