The role of presynaptic ryanodine-sensitive calcium stores in long-term depression.

摘要

Ca2+ release from internal stores is used to amplify and dynamically regulate cytosolic Ca2+ concentration in a wide variety of cells. In neurons, Ca2+ release from internal stores has been implicated in many regulatory events, including postsynaptic signaling, presynaptic control of transmitter release, and long-term synaptic plasticity. However, the importance of Ca2+ release for neuronal signaling remains controversial in some instances. Technical difficulties recording from small neuronal structures especially limit experiments in brain slices. Here I take advantage of recent advances in techniques to investigate the role of Ca2+ release in long-term depression (LTD) at the CA3-CA3 pyramidal neuron synapse in hippocampal slice culture.; My work on the role of internal Ca2+ stores in synaptic plasticity argues that ryanodine-sensitive stores are required in the presynaptic terminal for the induction of long-term depression (LTD). This conclusion is based on three lines of evidence. First, using dual whole-cell recording I have shown that selective application of inhibitors of ryanodine-sensitive stores to the presynaptic cell will prevent the induction of LTD, but have no affect when applied to the postsynaptic cell. Second, I have used two-photon laser scanning microscopy (TPLSM) to image Ca2+ in individual CA3 pyramidal neuron presynaptic terminals. During the LTD induction protocol there is a slowly rising Ca2+ signal in the presynaptic terminal that is blocked by the same ryanodine-sensitive store inhibitors that prevent LTD. And third, by using the styryl dye FM 1-43 as a marker of synaptic vesicle cycling, I have shown that inhibition of ryanodine-sensitive stores prevents changes in presynaptic release that are part of the expression mechanisms associated with LTD.; Given the prior demonstration of a role for ryanodine-sensitive stores during the induction of LTD at other synapses, these results indicate the conservation of certain mechanisms of LTD induction at diverse synapses in the brain. This demonstration and characterization of NMDA receptor-dependent LTD at the CA3-CA3 synapse, along with a study of possible structural changes associated with LTP, provide fundamental insights into the cellular and molecular mechanisms of important forms of long-term plasticity, as well as insight into the plastic capabilities of circuits that are likely to underlie memory storage in the mammalian brain.