Long-term depression triggers the selective elimination of weakly integrated synapses
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Long-term depression triggers the selective elimination of weakly integrated synapses. / Wiegert, J Simon; Oertner, Thomas G.
In: P NATL ACAD SCI USA, Vol. 110, No. 47, 19.11.2013, p. E4510-9.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Long-term depression triggers the selective elimination of weakly integrated synapses
AU - Wiegert, J Simon
AU - Oertner, Thomas G
PY - 2013/11/19
Y1 - 2013/11/19
N2 - Long-term depression (LTD) weakens synaptic transmission in an activity-dependent manner. It is not clear, however, whether individual synapses are able to maintain a depressed state indefinitely, as intracellular recordings rarely exceed 1 h. Here, we combine optogenetic stimulation of identified Schaffer collateral axons with two-photon imaging of postsynaptic calcium signals and follow the fate of individual synapses for 7 d after LTD induction. Optogenetic stimulation of CA3 pyramidal cells at 1 Hz led to strong and reliable depression of postsynaptic calcium transients in CA1. NMDA receptor activation was necessary for successful induction of LTD. We found that, in the days following LTD, many depressed synapses and their "neighbors" were eliminated from the hippocampal circuit. The average lifetime of synapses on nonstimulated dendritic branches of the same neurons remained unaffected. Persistence of individual depressed synapses was highly correlated with reliability of synaptic transmission, but not with spine size or the amplitude of spine calcium transients. Our data suggest that LTD initially leads to homogeneous depression of synaptic function, followed by selective removal of unreliable synapses and recovery of function in the persistent fraction.
AB - Long-term depression (LTD) weakens synaptic transmission in an activity-dependent manner. It is not clear, however, whether individual synapses are able to maintain a depressed state indefinitely, as intracellular recordings rarely exceed 1 h. Here, we combine optogenetic stimulation of identified Schaffer collateral axons with two-photon imaging of postsynaptic calcium signals and follow the fate of individual synapses for 7 d after LTD induction. Optogenetic stimulation of CA3 pyramidal cells at 1 Hz led to strong and reliable depression of postsynaptic calcium transients in CA1. NMDA receptor activation was necessary for successful induction of LTD. We found that, in the days following LTD, many depressed synapses and their "neighbors" were eliminated from the hippocampal circuit. The average lifetime of synapses on nonstimulated dendritic branches of the same neurons remained unaffected. Persistence of individual depressed synapses was highly correlated with reliability of synaptic transmission, but not with spine size or the amplitude of spine calcium transients. Our data suggest that LTD initially leads to homogeneous depression of synaptic function, followed by selective removal of unreliable synapses and recovery of function in the persistent fraction.
KW - Animals
KW - Calcium Signaling
KW - Electroporation
KW - Fluorescence
KW - Hippocampus
KW - Long-Term Synaptic Depression
KW - Neuronal Plasticity
KW - Optogenetics
KW - Patch-Clamp Techniques
KW - Pyramidal Cells
KW - Rats
KW - Rats, Wistar
KW - Rhodopsin
KW - Synapses
KW - Synaptic Transmission
U2 - 10.1073/pnas.1315926110
DO - 10.1073/pnas.1315926110
M3 - SCORING: Journal article
C2 - 24191047
VL - 110
SP - E4510-9
JO - P NATL ACAD SCI USA
JF - P NATL ACAD SCI USA
SN - 0027-8424
IS - 47
ER -
