A cortico-hippocampal learning rule shapes inhibitory microcircuit activity to enhance hippocampal information flow

Neuron. 2013 Sep 18;79(6):1208-21. doi: 10.1016/j.neuron.2013.07.001.

Abstract

How does coordinated activity between distinct brain regions implement a set of learning rules to sculpt information processing in a given neural circuit? Using interneuron cell-type-specific optical activation and pharmacogenetic silencing in vitro, we show that temporally precise pairing of direct entorhinal perforant path (PP) and hippocampal Schaffer collateral (SC) inputs to CA1 pyramidal cells selectively suppresses SC-associated perisomatic inhibition from cholecystokinin (CCK)-expressing interneurons. The CCK interneurons provide a surprisingly strong feedforward inhibitory drive to effectively control the coincident excitation of CA1 pyramidal neurons by convergent inputs. Thus, in-phase cortico-hippocampal activity provides a powerful heterosynaptic learning rule for long-term gating of information flow through the hippocampal excitatory macrocircuit by the silencing of the CCK inhibitory microcircuit.

Publication types

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

MeSH terms

  • Animals
  • Biophysics
  • Calcium / metabolism
  • Cerebral Cortex / physiology*
  • Channelrhodopsins
  • Cholecystokinin / genetics
  • Computer Simulation
  • Electric Stimulation
  • Excitatory Amino Acid Antagonists / pharmacology
  • GABA Antagonists / pharmacology
  • Hippocampus / cytology*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • In Vitro Techniques
  • Inhibitory Postsynaptic Potentials / drug effects
  • Luminescent Proteins / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Models, Neurological
  • Nerve Net / physiology*
  • Neural Pathways / physiology*
  • Neurons / drug effects
  • Neurons / physiology*
  • Optogenetics
  • Parvalbumins / genetics
  • Patch-Clamp Techniques
  • Synapses / drug effects
  • Synapses / physiology

Substances

  • Channelrhodopsins
  • Dlx5 protein, mouse
  • Excitatory Amino Acid Antagonists
  • GABA Antagonists
  • Homeodomain Proteins
  • Luminescent Proteins
  • Parvalbumins
  • Cholecystokinin
  • Calcium