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

Manuel Valero, Robert G. Averkin, Ivan Fernandez-Lamo, Juan Aguilar, Diego Lopez-Pigozzi, Jorge R. Brotons-Mas, Elena Cid, G. Tamás, Liset Menendez de la Prida

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Abstract

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. Valero et al. show how unsupervised clustering discloses a synaptic mechanism for CA1 firing selectivity during sharp-wave ripples. This mechanism is impaired in epileptic rats by collapsing cell-specific synaptic drives. This establishes new concepts in understanding selective neuronal firing.

Original languageEnglish
Pages (from-to)1234-1247.e7
JournalNeuron
Volume94
Issue number6
DOIs
Publication statusPublished - Jun 21 2017

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ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Valero, M., Averkin, R. G., Fernandez-Lamo, I., Aguilar, J., Lopez-Pigozzi, D., Brotons-Mas, J. R., Cid, E., Tamás, G., & Menendez de la Prida, L. (2017). Mechanisms for Selective Single-Cell Reactivation during Offline Sharp-Wave Ripples and Their Distortion by Fast Ripples. Neuron, 94(6), 1234-1247.e7. https://doi.org/10.1016/j.neuron.2017.05.032