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Columbia Dissertations and Theses > Doctoral Dissertations
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| Author(s): | DeCostanzo, Anthony Joseph |
| Title: | 12-lipoxygenase modulates 1-type calcium channel-dependent long term potentiation by regulating calcium influex through 1-type calcium channels |
| Physical Description: | vii, 131 leaves, bound. |
| Issue Date: | 2008 |
| Description: | Department: Pharmacology. UMI cat no. 3299255 Thesis (Ph. D.)--Columbia University, 2008. |
| Bookmark as: | http://hdl.handle.net/10022/AC:P:18430 |
| Full Text (ProQuest): | /ac/proxit.jsp?url=http://gateway.proquest.com/ope... |
| Abstract: | Hippocampal long-term potentiation (LTP) is generally believed to underlie learning and the consolidation of memories in the mammalian brain. At CA3-CA1 Schaffer collateral synapses one of two fundamental calcium channels must be recruited for the induction of LTP: the NMDA receptor or the L-type calcium channel (LTCC). Though more than twenty years have passed since the finding that NMDA receptors are required for the induction of rip at CA3-CA1 synapses there is little agreement as to the molecules that mediate and modulate LTP induction. This may be partly due to the failure to discriminate between NMDA-receptor dependent and LTCC-dependent forms of LTP, each of which appears to involve distinct signal transduction and modulatory mechanisms. A previous study from our laboratory demonstrated that 12-lipoxygenase (12LOX) mediates metabotropic glutamate receptor-dependent long-term depression (mGluR-LTD), a form of LTCC-dependent plasticity present in neonates. I therefore tested the hypothesis that 12LOX is a general mediator of LTCC-dependent plasticity at CA3-CA1 synapses by measuring LTCC-dependent LTP in adult hippocampal slices from a 12LOX knockout mouse. Herein I describe that, in contrast to its role as a downstream mediator of LTCC-dependent plasticity in the neonate, 12LOX is a selective upstream modulator of adult LTCC-dependent LTP, an action exerted via its regulation of calcium influx through LTCCs. |
| Collection(s): | Doctoral Dissertations |
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