Impaired Cerebellar Long-Term Potentiation in Type I Adenylyl Cyclase Mutant Mice

Neuron. 1998 Jun;20(6):1199-210. doi: 10.1016/s0896-6273(00)80500-0.

Abstract

Activation of adenylyl cyclase and the consequent production of cAMP is a process that has been shown to be central to invertebrate model systems of information storage. In the vertebrate brain, it has been suggested that a presynaptic cascade involving Ca influx, cAMP production, and subsequent activation of cAMP-dependent protein kinase is necessary for induction of long-term potentiation (LTP) at the cerebellar parallel fiber-Purkinje cell synapse. We have used mutant mice in which the major Ca-sensitive adenylyl cyclase isoform of cerebellar cortex (type I) is deleted to show that this results in an approximately 65% reduction in cerebellar Ca-sensitive cyclase activity and a nearly complete blockade of cerebellar LTP assessed using granule cell-Purkinje cell pairs in culture. This blockade is not accompanied by alterations in a number of basal electrophysiological parameters and may be bypassed by application of an exogenous cAMP analog, suggesting that it results specifically from deletion of the type I adenylyl cyclase.

Publication types

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

MeSH terms

  • Adenylyl Cyclases / genetics*
  • Adenylyl Cyclases / metabolism
  • Animals
  • Cell Membrane / enzymology
  • Cells, Cultured
  • Cyclic AMP / analogs & derivatives
  • Cyclic AMP / metabolism
  • Cyclic AMP / pharmacology
  • Electrophysiology
  • Enzyme Inhibitors / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • Gait / physiology
  • Glutamic Acid / pharmacology
  • Long-Term Potentiation / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mutation / physiology
  • Nerve Fibers / enzymology
  • Psychomotor Performance / physiology
  • Purkinje Cells / cytology
  • Purkinje Cells / enzymology*
  • Purkinje Cells / ultrastructure
  • Thionucleotides / pharmacology

Substances

  • Enzyme Inhibitors
  • Thionucleotides
  • Glutamic Acid
  • 8-((4-chlorophenyl)thio)cyclic-3',5'-AMP
  • Cyclic AMP
  • Adenylyl Cyclases