Low excitatory innervation balances high intrinsic excitability of immature dentate neurons

Nat Commun. 2016 Apr 20:7:11313. doi: 10.1038/ncomms11313.

Abstract

Persistent neurogenesis in the dentate gyrus produces immature neurons with high intrinsic excitability and low levels of inhibition that are predicted to be more broadly responsive to afferent activity than mature neurons. Mounting evidence suggests that these immature neurons are necessary for generating distinct neural representations of similar contexts, but it is unclear how broadly responsive neurons help distinguish between similar patterns of afferent activity. Here we show that stimulation of the entorhinal cortex in mouse brain slices paradoxically generates spiking of mature neurons in the absence of immature neuron spiking. Immature neurons with high intrinsic excitability fail to spike due to insufficient excitatory drive that results from low innervation rather than silent synapses or low release probability. Our results suggest that low synaptic connectivity prevents immature neurons from responding broadly to cortical activity, potentially enabling excitable immature neurons to contribute to sparse and orthogonal dentate representations.

Publication types

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

MeSH terms

  • Animals
  • Dentate Gyrus / cytology
  • Dentate Gyrus / drug effects
  • Dentate Gyrus / physiology*
  • Electric Stimulation
  • Entorhinal Cortex / cytology
  • Entorhinal Cortex / drug effects
  • Entorhinal Cortex / physiology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology*
  • Female
  • Gene Expression
  • Integrases / genetics
  • Integrases / metabolism
  • Male
  • Mice
  • Mice, Transgenic
  • Microtomy
  • N-Methylaspartate / pharmacology
  • Nestin / genetics
  • Nestin / metabolism
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology*
  • Neural Stem Cells / drug effects
  • Neural Stem Cells / physiology
  • Neurogenesis / drug effects
  • Neurogenesis / physiology*
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology
  • Neurons / drug effects
  • Neurons / physiology*
  • Patch-Clamp Techniques
  • Pyridazines / pharmacology
  • Synapses / drug effects
  • Synapses / physiology*
  • Tamoxifen / pharmacology
  • Tissue Culture Techniques
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology

Substances

  • Nes protein, mouse
  • Nestin
  • Pyridazines
  • Tamoxifen
  • N-Methylaspartate
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
  • gabazine
  • Cre recombinase
  • Integrases