Real Time Multiplicative Memory Amplification Mediated by Whole-Cell Scaling of Synaptic Response in Key Neurons

Iris Reuveni, Sourav Ghosh, Edi Barkai

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Intense spiking response of a memory-pattern is believed to play a crucial role both in normal learning and pathology, where it can create biased behavior. We recently proposed a novel model for memory amplification where the simultaneous two-fold increase of all excitatory (AMPAR-mediated) and inhibitory (GABAAR-mediated) synapses in a sub-group of cells that constitutes a memory-pattern selectively amplifies this memory. Here we confirm the cellular basis of this model by validating its major predictions in four sets of experiments, and demonstrate its induction via a whole-cell transduction mechanism. Subsequently, using theory and simulations, we show that this whole-cell two-fold increase of all inhibitory and excitatory synapses functions as an instantaneous and multiplicative amplifier of the neurons’ spiking. The amplification mechanism acts through multiplication of the net synaptic current, where it scales both the average and the standard deviation of the current. In the excitation-inhibition balance regime, this scaling creates a linear multiplicative amplifier of the cell’s spiking response. Moreover, the direct scaling of the synaptic input enables the amplification of the spiking response to be synchronized with rapid changes in synaptic input, and to be independent of previous spiking activity. These traits enable instantaneous real-time amplification during brief elevations of excitatory synaptic input. Furthermore, the multiplicative nature of the amplifier ensures that the net effect of the amplification is large mainly when the synaptic input is mostly excitatory. When induced on all cells that comprise a memory-pattern, these whole-cell modifications enable a substantial instantaneous amplification of the memory-pattern when the memory is activated. The amplification mechanism is induced by CaMKII dependent phosphorylation that doubles the conductance of all GABAAand AMPA receptors in a subset of neurons. This whole-cell transduction mechanism enables both long-term induction of memory amplification when necessary and extinction when not further required.

Original languageEnglish
Article numbere1005306
JournalPLoS Computational Biology
Volume13
Issue number1
DOIs
StatePublished - 1 Jan 2017
Externally publishedYes

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Modeling and Simulation
  • Ecology
  • Molecular Biology
  • Genetics
  • Cellular and Molecular Neuroscience
  • Computational Theory and Mathematics

Fingerprint

Dive into the research topics of 'Real Time Multiplicative Memory Amplification Mediated by Whole-Cell Scaling of Synaptic Response in Key Neurons'. Together they form a unique fingerprint.

Cite this