Calcium-dependent PKC isoforms have specialized roles in short-term synaptic plasticity

Neuron. 2014 May 21;82(4):859-71. doi: 10.1016/j.neuron.2014.04.003. Epub 2014 May 1.


Posttetanic potentiation (PTP) is a widely observed form of short-term plasticity lasting for tens of seconds after high-frequency stimulation. Here we show that although protein kinase C (PKC) mediates PTP at the calyx of Held synapse in the auditory brainstem before and after hearing onset, PTP is produced primarily by an increased probability of release (p) before hearing onset, and by an increased readily releasable pool of vesicles (RRP) thereafter. We find that these mechanistic differences, which have distinct functional consequences, reflect unexpected differential actions of closely related calcium-dependent PKC isoforms. Prior to hearing onset, when PKCγ and PKCβ are both present, PKCγ mediates PTP by increasing p and partially suppressing PKCβ actions. After hearing onset, PKCγ is absent and PKCβ produces PTP by increasing RRP. In hearing animals, virally expressed PKCγ overrides PKCβ to produce PTP by increasing p. Thus, two similar PKC isoforms mediate PTP in distinctly different ways.

Publication types

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

MeSH terms

  • Age Factors
  • Animals
  • Animals, Newborn
  • Benzothiadiazines / pharmacology
  • Calcium / metabolism
  • Enzyme Inhibitors / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Gene Expression Regulation, Developmental / genetics
  • In Vitro Techniques
  • Kynurenic Acid / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neuronal Plasticity / genetics
  • Neuronal Plasticity / physiology
  • Neurons / physiology*
  • Pons / cytology*
  • Presynaptic Terminals / metabolism
  • Protein Isoforms / deficiency
  • Protein Isoforms / metabolism*
  • Protein Kinase C / deficiency
  • Protein Kinase C / metabolism*
  • Synapses / physiology*
  • Vesicular Glutamate Transport Protein 1 / metabolism


  • Benzothiadiazines
  • Enzyme Inhibitors
  • Excitatory Amino Acid Antagonists
  • Protein Isoforms
  • Vesicular Glutamate Transport Protein 1
  • Protein Kinase C
  • Kynurenic Acid
  • cyclothiazide
  • Calcium