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 ~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.
Original language | English (US) |
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Pages (from-to) | 1199-1210 |
Number of pages | 12 |
Journal | Neuron |
Volume | 20 |
Issue number | 6 |
DOIs | |
State | Published - Jun 1998 |
ASJC Scopus subject areas
- General Neuroscience