Endocannabinoids Lower the LTP Threshold

Abstract

Endocannabinoids have been implicated in various forms of synaptic depression (see Related Resources and Fitzjohn and Collingridge). Chevaleyre and Castillo demonstrate that endocannabinoid-mediated long-term depression of inhibitory synapses (I-LTD) in the hippocampus lowers the threshold for the induction of long-term potentiation (LTP) of nearby excitatory synapses. Only theta-burst stimuli (TBS) that were close (10 μm) to the site of the induced inhibitory postsynaptic potentials (IPSPs) produced I-LTD. (TBS is a well-established repetitive stimulation protocol that can produce long-term synaptic changes.) Using a stimulation frequency that produced I-LTD, but not LTP in the excitatory Schaffer collateral to CA1 synapses, the authors triggered I-LTD and then investigated the magnitude of the LTP produced in response to subsequent stimuli. LTP magnitude was larger following priming by I-LTD, and this effect required GABA A ion channels and the CB1 endocannabinoid receptor. The authors suggest that repetitive stimulation produces LTP directly in a restricted region and I-LTD in a wider region, because lower stimulation frequencies are required, and this I-LTD facilitates the induction of LTP in synapses adjacent to those directly receiving the repetitive stimuli. S. M. Fitzjohn, G. L. Collingridge, Endocannabinoids: Losing inhibition to increase learning capacity? Neuron 43 , 762-764 (2004). [Online Journal] V. Chevaleyre, P. E. Castillo, Endocannabinoid-mediated metaplasticity in the hippocampus. Neuron 43 , 871-881 (2004). [Online Journal]