PSD-95 is required for activity-driven synapse stabilization.
The activity-dependent regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors and the stabilization of synapses are critical to synaptic development and plasticity. One candidate molecule implicated in maturation, synaptic strengthening, and plasticity is PSD-95. Here we find that acute knockdown of PSD-95 in brain slice cultures by RNAi arrests the normal development of synaptic structure and function that is driven by spontaneous activity. Surprisingly, PSD-95 is not necessary for the induction and early expression of long-term potentiation (LTP). However, knockdown of PSD-95 leads to smaller increases in spine size after chemically induced LTP. Furthermore, although at this age spine turnover is normally low and LTP produces a transient increase, in cells with reduced PSD-95 spine turnover is high and remains increased after LTP. Taken together, our data support a model in which appropriate levels of PSD-95 are required for activity-dependent synapse stabilization after initial phases of synaptic potentiation.
Ehrlich
Ingrid
I
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA. ingrid.ehrlich@fmi.ch
Klein
Matthew
M
Rumpel
Simon
S
Malinow
Roberto
R
D000818:Animals; D001921:Brain / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism; D000076122:Disks Large Homolog 4 Protein; D004594:Electrophysiology; D005973:Glutamine / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism / Q000502:physiology*; D017774:Long-Term Potentiation; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D009473:Neuronal Plasticity; D034622:RNA Interference; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism* / Q000473:pathology; D009435:Synaptic Transmission
D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D018091:Receptors, AMPA; D005973:Glutamine