Fos and Jun are transcription factors that heterodimerize to form AP-1, a transcriptional activator complex. They are two among many important candidate immediate early genes long hypothesized to function as transcriptional gatekeepers between the short-term and long-term modifications of synaptic efficacy postulated to underlie learning and memory. In normally active Drosophila motor neurons, overexpression of AP-1, induces cAMP- and CREB- dependent forms of synaptic enhancement. The activities of immediate early genes such as fos, jun, and CREB have long been assumed to achieve synaptic enhancement by increasing synapse number. We show that at the Drosophila neuromuscular junction (NMJ), an AP-1- and CREB- dependent form of presynaptic strengthening is mediated by increasing the weights of unitary synapses and not through the insertion of additional release sites. Post-tetanic potentiation (PTP) is reduced at these synapses, suggesting that the mechanisms underlying this short-term form of synaptic enhancement may be stably recruited by pathways activated downstream of AP-1 overexpression. Electrophysiological and FM1-43 based measurements further demonstrate that enhanced neurotransmitter release is accompanied by an increase in the actively cycling synaptic-vesicle pool at the expense of the reserve pool. Increases in both transmitter release and cycling-pool size are blocked under conditions of CREB inhibition arguing that: a) AP-1 and CREB are required for reserve-pool mobilization; and b) that sustained reserve pool mobilization may underlie this form of plasticity. These findings together suggest transcriptional mechanisms believed to participate in long-term forms of synaptic enhancement may, in some instances, be accomplished by the stable recruitment of mechanisms that normally underlie short-term synaptic change.
| Identifer | oai:union.ndltd.org:arizona.edu/oai:arizona.openrepository.com:10150/193677 |
| Date | January 2007 |
| Creators | Kim, Susy M. |
| Contributors | Zinsmaier, Konrad E., Gronenberg, Wulfila, Nighorn, Alan, Levine, Richard B. |
| Publisher | The University of Arizona. |
| Source Sets | University of Arizona |
| Language | English |
| Detected Language | English |
| Type | text, Electronic Dissertation |
| Rights | Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author. |
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