title: Activity-dependent actin dynamics are required for the maintenance of long-term plasticity and for synaptic capture.
abstract: The maintenance of long-lasting forms of plasticity, such as long-term potentiation (LTP) is dependent on the capture of plasticity-related proteins (PRPs) in an input-specific manner - synaptic capture. Here, it is shown that LTP, induced at Schaffer collaterals-CA1 synapses in acute rat hippocampal slice preparation, is not sensitive to protein synthesis inhibition if N-methyl-d-aspartate (NMDA) receptors are blocked, suggesting that synaptic activation is involved in the modulation of LTP maintenance. Similarly, it was found that synaptic activation also determines the sensitivity of LTP to manipulations of the actin cytoskeleton dynamics. Suspending synaptic activation or concomitant NMDA receptor inhibition is sufficient to rescue the impairment on LTP maintenance induced by actin polymerization blockade. Additionally, concomitant inhibition of protein degradation can partially prevent the LTP decay observed under actin polymerization blockade, suggesting that protein degradation is involved in the destabilization of LTP maintenance induced by actin polymerization blockade. Taken together, these observations suggest that LTP maintenance is determined by a balance of synthesis and degradation of PRPs modulated by synaptic activation and actin dynamics. Finally, it was uncovered that inhibition of actin depolymerization blocks synaptic capture, whereas inhibition of actin polymerization can extend the temporal window for synaptic capture. Additionally, inhibition of actin polymerization can rescue the impairment in synaptic capture induced by CaMKII inhibition, suggesting a link between CaMKII activation and modulation of actin dynamics during synaptic capture. These results show that an activity-dependent regulation of actin dynamics plays a critical role in LTP maintenance and synaptic capture.
authors.affiliation: Champalimaud Neuroscience Programme at Instituto Gulbenkian de Ciência, Rua da Quinta Grande, Oeiras, Portugal. rfonseca@igc.gulbenkian.pt
authors.forename: Rosalina
authors.initials: R
authors.lastname: Fonseca
mesh_terms: D000199:Actins / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D003599:Cytoskeleton / Q000737:chemistry / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006624:Hippocampus / Q000737:chemistry / Q000502:physiology; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000737:chemistry / Q000378:metabolism; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D058105:Polymerization; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D000199:Actins; D016194:Receptors, N-Methyl-D-Aspartate