Synaptic excitation produces a long-lasting rebound potentiation of inhibitory synaptic signals in cerebellar Purkinje cells

Nature. 1992 Apr 16;356(6370):601-4. doi: 10.1038/356601a0.

Abstract

Persistent changes in synaptic efficacy are thought to underlie the formation of learning and memory in the brain. High-frequency activation of an afferent excitatory fibre system can induce long-term potentiation, and conjunctive activation of two distinct excitatory synaptic inputs to the cerebellar Purkinje cells can lead to long-term depression of the synaptic activity of one of the inputs. Here we report a new form of neural plasticity in which activation of an excitatory synaptic input can induce a potentiation of inhibitory synaptic signals to the same cell. In cerebellar Purkinje cells stimulation of the excitatory climbing fibre synapses is followed by a long-lasting (up to 75 min) potentiation of gamma-aminobutyric acid A (GABAA) receptor-mediated inhibitory postsynaptic currents (i.p.s.cs), a phenomenon that we term rebound potentiation. Using whole-cell patch-clamp recordings in combination with fluorometric video imaging of intracellular calcium ion concentration, we find that a climbing fibre-induced transient increase in postsynaptic calcium concentration triggers the induction of rebound potentiation. Because the response of Purkinje cells to bath-applied exogenous GABA is also potentiated after climbing fibre-stimulation with a time course similar to that of the rebound potentiation of i.p.s.cs, we conclude that the potentiation is caused by a calcium-dependent upregulation of postsynaptic GABAA receptor function. We propose that rebound potentiation is a mechanism by which in vivo block of climbing fibre activity induces an increase in excitability in Purkinje cells. Moreover, rebound potentiation of i.p.s.cs is a cellular mechanism which, in addition to the long-term depression of parallel fibre synaptic activity, may have an important role for motor learning in the cerebellum.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bicuculline / pharmacology
  • Calcium / physiology
  • Dendrites / drug effects
  • Dendrites / physiology
  • Egtazic Acid / analogs & derivatives
  • Egtazic Acid / pharmacology
  • Electric Stimulation
  • Evoked Potentials / drug effects
  • In Vitro Techniques
  • Membrane Potentials / drug effects
  • Microscopy, Fluorescence
  • Purkinje Cells / cytology
  • Purkinje Cells / drug effects
  • Purkinje Cells / physiology*
  • Rats
  • Receptors, GABA-A / drug effects
  • Receptors, GABA-A / physiology
  • Signal Transduction
  • Synapses / drug effects
  • Synapses / physiology*
  • gamma-Aminobutyric Acid / pharmacology*

Substances

  • Receptors, GABA-A
  • Egtazic Acid
  • gamma-Aminobutyric Acid
  • 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
  • Calcium
  • Bicuculline