Independent expression of synaptic and morphological plasticity associated with long-term depression.

Physiological and morphological alterations occur with long-term synaptic modifications, such as long-term potentiation (LTP) and long-term depression (LTD), but whether these two processes are independent or interactive is unclear. It is also unknown whether or how morphological modifications, like spine remodeling, may contribute to physiological modifications, such as trafficking of glutamate receptors which underlies, at least partially, the expression of LTP and LTD. In this study, we monitored spine size and synaptic responses simultaneously using combined two photon time-lapse imaging with patch-clamp recording in acute hippocampal slices. We show that spine shrinkage and LTD can occur independently of each other. We further show that changes in spine size are unrelated to trafficking of AMPA receptors (AMPARs) under various conditions: constitutive trafficking of AMPARs, insulin-induced internalization of AMPARs, or lateral movement of AMPARs to extrasynaptic sites. Induction of LTD of NMDA receptor-mediated responses (NMDAR-LTD) is associated with spine shrinkage. Nonetheless, NMDAR-LTD and spine shrinkage diverge in the downstream signaling events, and can occur independently of each other. Thus, spine shrinkage is not caused by or required for trafficking of glutamate receptors. In a broader sense, there is a clear dissociation between physiological and morphological expression of LTD. However, inhibition of actin depolymerization blocked the expression of LTD, suggesting that morphologically silent actin remodeling may be involved in the physiological expression of LTD and different subpopulations of actin filaments undergo changes during LTD.