Adaptive regulation maintains posttetanic potentiation at cerebellar granule cell synapses in the absence of calcium-dependent PKC

J Neurosci. 2012 Sep 19;32(38):13004-9. doi: 10.1523/JNEUROSCI.0683-12.2012.


Posttetanic potentiation (PTP) is a transient, calcium-dependent increase in the efficacy of synaptic transmission following elevated presynaptic activity. The calcium-dependent protein kinase C (PKC(Ca)) isoforms PKCα and PKCβ mediate PTP at the calyx of Held synapse, with PKCβ contributing significantly more than PKCα. It is not known whether PKC(Ca) isoforms play a conserved role in PTP at other synapses. We examined this question at the parallel fiber → Purkinje cell (PF→PC) synapse, where PKC inhibitors suppress PTP. We found that PTP is preserved when single PKC(Ca) isoforms are knocked out and in PKCα/β double knock-out (dko) mice, even though in the latter all PKC(Ca) isoforms are eliminated from granule cells. However, in contrast to wild-type and single knock-out animals, PTP in PKCα/β dko animals is not suppressed by PKC inhibitors. These results indicate that PKC(Ca) isoforms mediate PTP at the PF→PC synapse in wild-type and single knock-out animals. However, unlike the calyx of Held, at the PF→PC synapse either PKCα or PKCβ alone is sufficient to mediate PTP, and if both isoforms are eliminated a compensatory PKC-independent mechanism preserves the plasticity. These results suggest that a feedback mechanism allows granule cells to maintain the normal properties of short-term synaptic plasticity even when the mechanism that mediates PTP in wild-type mice is eliminated.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptation, Physiological / genetics
  • Adaptation, Physiological / physiology*
  • Analysis of Variance
  • Animals
  • Animals, Newborn
  • Biophysics
  • Calcium / metabolism*
  • Cerebellum / cytology*
  • Electric Stimulation
  • Enzyme Inhibitors / pharmacology
  • Excitatory Postsynaptic Potentials / genetics
  • Excitatory Postsynaptic Potentials / physiology*
  • Female
  • GABA Agents / pharmacology
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / genetics
  • In Vitro Techniques
  • Male
  • Mice
  • Mice, Knockout
  • Neurons / physiology*
  • Patch-Clamp Techniques
  • Piperidines / pharmacology
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / physiology
  • Protein Kinase C / deficiency
  • Protein Kinase C / metabolism*
  • Protein Kinase C beta
  • Protein Kinase C-alpha / deficiency
  • Protein Kinase C-alpha / metabolism*
  • Pyrazoles / pharmacology


  • Enzyme Inhibitors
  • GABA Agents
  • Piperidines
  • Pyrazoles
  • AM 251
  • Protein Kinase C
  • Protein Kinase C beta
  • Protein Kinase C-alpha
  • Calcium