Developmental regulation of CB1-mediated spike-time dependent depression at immature mossy fiber-CA3 synapses

Maddalena D. Caiati, Sudhir Sivakumaran, Frederic Lanore, Christophe Mulle, Elodie Richard, Dany Verrier, Giovanni Marsicano, Richard Miles, Enrico Cherubini
Sci Rep. 2012-02-24; 2(1):
DOI: 10.1038/srep00285

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Early in postnatal life, mossy fibres (MF), the axons of granule cells in the
dentate gyrus, release GABA which is depolarizing and excitatory. Synaptic
currents undergo spike-time dependent long-term depression (STD-LTD) regardless
of the temporal order of stimulation (pre versus post and viceversa). Here we
show that at P3 but not at P21, STD-LTD, induced by negative pairing, is mediated
by endocannabinoids mobilized from the postsynaptic cell during spiking-induced
membrane depolarization. By diffusing backward, endocannabinoids activate
cannabinoid type-1 (CB1) receptors probably expressed on MF. Thus, STD-LTD was
prevented by CB1 receptor antagonists and was absent in CB1-KO mice. Consistent
with these data, in situ hybridization experiments revealed detectable level of
CB1 mRNA in the granule cell layer at P3 but not at P21. These results indicate
that CB1 receptors are transiently expressed on immature MF terminals where they
counteract the enhanced neuronal excitability induced by the excitatory action of


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