First Author | Storm DR | Year | 1998 |
Journal | Neuron | Volume | 20 |
Issue | 6 | Pages | 1199-210 |
PubMed ID | 9655507 | Mgi Jnum | J:77293 |
Mgi Id | MGI:2181321 | Doi | 10.1016/s0896-6273(00)80500-0 |
Citation | Storm DR, et al. (1998) Impaired cerebellar long-term potentiation in type I adenylyl cyclase mutant mice. Neuron 20(6):1199-210 |
abstractText | 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. |