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

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

Abstract

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.

Keywords: Circuit connections; hippocampus; imaging; quantitative; viral tracing.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • CA1 Region, Hippocampal / cytology*
  • CA1 Region, Hippocampal / physiology*
  • CA3 Region, Hippocampal / cytology
  • CA3 Region, Hippocampal / physiology
  • Entorhinal Cortex / cytology
  • Entorhinal Cortex / physiology
  • Immunohistochemistry
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neural Pathways / cytology
  • Neural Pathways / physiology
  • Neuroanatomical Tract-Tracing Techniques
  • Neurons / cytology*
  • Neurons / physiology*
  • Parahippocampal Gyrus / cytology
  • Parahippocampal Gyrus / physiology
  • Raphe Nuclei / cytology
  • Raphe Nuclei / physiology
  • Septum of Brain / cytology
  • Septum of Brain / physiology
  • Voltage-Sensitive Dye Imaging