Postsynaptic density-95 mimics and occludes hippocampal long-term potentiation and enhances long-term depression - PubMed (original) (raw)

Postsynaptic density-95 mimics and occludes hippocampal long-term potentiation and enhances long-term depression

Valentin Stein et al. J Neurosci. 2003.

Abstract

Previous studies have shown that overexpression of the protein PSD-95 (postsynaptic density-95) selectively enhances AMPA receptor-mediated synaptic responses in hippocampal pyramidal cells. To determine whether this effect is related to synaptic plasticity at these synapses, we examined whether PSD-95 expression mimics long-term potentiation (LTP), and also whether it influences LTP and long-term depression (LTD) in hippocampal slice cultures. Using simultaneous recording from transfected or infected cells and control pyramidal cells, we found that PSD-95, similar to LTP, increases the amplitude and frequency of miniature EPSCs. It also converts silent synapses to functional synapses, as does LTP. In addition, LTP is completely occluded in cells expressing PSD-95, whereas LTD is greatly enhanced. These results suggest that common mechanisms are involved in controlling synaptic AMPA receptors by PSD-95 and synaptic plasticity.

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Figures

Figure 1.

Figure 1.

Expression of PSD-95 enhances the amplitude and frequency of mEPSCs. A, Five superimposed sample traces showing mEPSCs from a control cell (left) and a PSD-95-expressing cell (right). Note that there are many more events in the PSD-95-expressing cell, and that some of the events are larger than events recorded in a control cell. B, Cumulative frequency distributions of the amplitudes of mEPSCs recorded from control cells (closed circles) and PSD-95-expressing cells (open circles) (n = 7). C, Cumulative frequency distributions of the interevent intervals of mEPSCs recorded in control cells (closed circles) and PSD-95-expressing cells (open circles).

Figure 2.

Figure 2.

Expression of PSD-95 inserts AMPA receptors into silent synapses. A, Ten superimposed traces showing responses to minimal stimulation from a control cell (left) and a PSD-95-expressing cell (right). Arrows indicate when the stimulus was delivered. Note that there are many fewer failures, and that the responses are much larger in the PSD-95-expressing cell. B, Averaged records of all traces at –70 and +40 mV. Note that the NMDA component is the same in the two cells, whereas the AMPA component is much larger in the PSD-95-expressing cell. The NMDA component was measured 55 msec after the stimulus, as indicated by the dashed line. C, Plots of EPSC amplitude versus trial number at –70 and +40 mV for the control cell (left) and PSD-95-expressing cell (right). D, EPSC amplitude distribution (solid line) and noise (broken line) in the control cell (left) and the PSD-95 expressing cell (right). See Materials and Methods for calculating noise. E, A pair-wise comparison of the failure rate between control and PSD-95-expressing cells. See Materials and Methods for estimating failure rate. F, A pair-wise comparison of the size of the NMDA EPSC recorded at +40 mV. The symbol for each pair is the same as that used in E.

Figure 3.

Figure 3.

Expression of PSD-95 occludes LTP. A, Graph comparing LTP recorded simultaneously from control neurons (closed circles) and neurons expressing PSD-95 (open circles). The number of cells for both graphs is initially 10 and decreases to five by the end. Arrow indicates the time of pairing. B, Sample records from a pair of neurons showing EPSCs recorded before pairing (solid lines) and after pairing (dotted lines).

Figure 4.

Figure 4.

Expression of PSD-95 enhances LTD. A, Graph comparing LTD recorded simultaneously from control neurons (closed circles) and from neurons expressing PSD-95 (open circles). The number of cells for the control graph is initially 11 and decreases to six by the end of the experiments. For the graph of the cells expressing PSD-95, the number of cells is initially 11 and decreases to five by the end of the experiment. B, Sample records from a pair of neurons showing EPSCs recorded before pairing (solid lines) and after pairing (dotted lines).

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