Mechanisms for Selective Single-Cell Reactivation during Offline Sharp-Wave Ripples and Their Distortion by Fast Ripples

Neuron. 2017 Jun 21;94(6):1234-1247.e7. doi: 10.1016/j.neuron.2017.05.032.


Memory traces are reactivated selectively during sharp-wave ripples. The mechanisms of selective reactivation, and how degraded reactivation affects memory, are poorly understood. We evaluated hippocampal single-cell activity during physiological and pathological sharp-wave ripples using juxtacellular and intracellular recordings in normal and epileptic rats with different memory abilities. CA1 pyramidal cells participate selectively during physiological events but fired together during epileptic fast ripples. We found that firing selectivity was dominated by an event- and cell-specific synaptic drive, modulated in single cells by changes in the excitatory/inhibitory ratio measured intracellularly. This mechanism collapses during pathological fast ripples to exacerbate and randomize neuronal firing. Acute administration of a use- and cell-type-dependent sodium channel blocker reduced neuronal collapse and randomness and improved recall in epileptic rats. We propose that cell-specific synaptic inputs govern firing selectivity of CA1 pyramidal cells during sharp-wave ripples.

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Anticonvulsants / pharmacology
  • Brain Waves / drug effects
  • CA1 Region, Hippocampal / cytology
  • CA1 Region, Hippocampal / drug effects
  • CA1 Region, Hippocampal / physiopathology
  • Carbamazepine / pharmacology
  • Disease Models, Animal
  • Electroencephalography
  • Epilepsy / physiopathology
  • Epilepsy, Temporal Lobe / physiopathology*
  • Epilepsy, Temporal Lobe / psychology
  • Hippocampus / cytology
  • Hippocampus / drug effects
  • Hippocampus / physiopathology*
  • Memory / drug effects
  • Memory Disorders / physiopathology*
  • Memory Disorders / psychology
  • Memory, Episodic
  • Neural Inhibition
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / physiology*
  • Rats
  • Rats, Wistar
  • Recognition, Psychology / drug effects
  • Recognition, Psychology / physiology*


  • Anticonvulsants
  • Carbamazepine