Synaptic Mechanisms Underlying the Network State-Dependent Recruitment of VIP-Expressing Interneurons in the CA1 Hippocampus

Cereb Cortex. 2020 May 18;30(6):3667-3685. doi: 10.1093/cercor/bhz334.

Abstract

Disinhibition is a widespread circuit mechanism for information selection and transfer. In the hippocampus, disinhibition of principal cells is provided by the interneuron-specific interneurons that express the vasoactive intestinal polypeptide (VIP-IS) and innervate selectively inhibitory interneurons. By combining optophysiological experiments with computational models, we determined the impact of synaptic inputs onto the network state-dependent recruitment of VIP-IS cells. We found that VIP-IS cells fire spikes in response to both the Schaffer collateral and the temporoammonic pathway activation. Moreover, by integrating their intrinsic and synaptic properties into computational models, we predicted recruitment of these cells between the rising phase and peak of theta oscillation and during ripples. Two-photon Ca2+-imaging in awake mice supported in part the theoretical predictions, revealing a significant speed modulation of VIP-IS cells and their preferential albeit delayed recruitment during theta-run epochs, with estimated firing at the rising phase and peak of the theta cycle. However, it also uncovered that VIP-IS cells are not activated during ripples. Thus, given the preferential theta-modulated firing of VIP-IS cells in awake hippocampus, we postulate that these cells may be important for information gating during spatial navigation and memory encoding.

Keywords: calretinin; disinhibition; network oscillations; ripples; theta.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology*
  • Animals
  • CA1 Region, Hippocampal / cytology
  • CA1 Region, Hippocampal / metabolism*
  • CA1 Region, Hippocampal / physiology
  • Computer Simulation
  • Interneurons / metabolism*
  • Interneurons / physiology
  • Memory
  • Mice
  • Mice, Transgenic
  • Neural Inhibition / physiology
  • Optical Imaging
  • Patch-Clamp Techniques
  • Recruitment, Neurophysiological / physiology
  • Spatial Memory / physiology
  • Spatial Navigation / physiology
  • Theta Rhythm
  • Vasoactive Intestinal Peptide / metabolism*
  • Wakefulness

Substances

  • Vasoactive Intestinal Peptide

Grants and funding