Extrinsic control and intrinsic computation in the hippocampal CA1 circuit

Neuron. 2022 Feb 16;110(4):658-673.e5. doi: 10.1016/j.neuron.2021.11.015. Epub 2021 Dec 9.


In understanding circuit operations, a key problem is the extent to which neuronal spiking reflects local computation or responses to upstream inputs. We addressed this issue in the hippocampus by performing combined optogenetic and pharmacogenetic local and upstream inactivation. Silencing the medial entorhinal cortex (mEC) largely abolished extracellular theta and gamma currents in CA1 while only moderately affecting firing rates. In contrast, CA3 and local CA1 silencing strongly decreased firing of CA1 neurons without affecting theta currents. Each perturbation reconfigured the CA1 spatial map. However, the ability of the CA1 circuit to support place field activity persisted, maintaining the same fraction of spatially tuned place fields and reliable assembly expression as in the intact mouse. Thus, the CA1 network can induce and maintain coordinated cell assemblies with minimal reliance on its inputs, but these inputs can effectively reconfigure and assist in maintaining stability of the CA1 map.

Keywords: CA1; CA3; entorhinal cortex; hippocampus; place cells; theta oscillations; theta phase preference.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Action Potentials / physiology
  • Animals
  • CA1 Region, Hippocampal / physiology
  • Entorhinal Cortex / physiology
  • Hippocampus* / physiology
  • Mice
  • Neurons
  • Optogenetics
  • Theta Rhythm* / physiology