Aim: 

Dynamin is a key protein mediating membrane fission in the endocytic process. Mutation of dynamin induces the disruption of neurotransmission after repeated stimuli in Drosophila melanogaster Conversely, dynamin inhibition by dynasore has no immediate effect on exocytosis while it is able to fully disrupt endocytosis in primary rat hippocampal neurons. Here, we have investigated the role of dynamin-mediated endocytosis in synaptic plasticity and memory in mice.

Methods: 

We performed electrophysiological recordings and behavioural tests on C57Bl/6J mice. Drug and vehicle were delivered in bath perfusion and through intrahippocampal cannulas.

Results: 

Dynasore (80 mM) disrupts both theta burst-induced long-term potentiation (LTP) at the CA3-CA1 hippocampal connection and contextual but not cued fear memory in mice. This effect was likely due to a reduction of the neurotransmitter released during the induction of LTP by the high-frequency stimulation. Indeed, post-tetanic potentiation was reduced and synaptic fatigue evoked with a 100 Hz stimulus for 1 second was enhanced in dynasore-treated slices. Moreover, paired-pulse facilitation and selective post-synaptic LTP induced by triple 50 Hz 1 s tetanus were not affected.

Conclusion: 

Taken together, these findings support the hypothesis that endocytosis plays a key role in synaptic plasticity and memory.

Supported by NIH Grant NS049442 to O.A.