Temporal gating of synaptic competition in the lateral amygdala by cannabinoid receptor modulation of the thalamic input

Abstract

The acquisition of fear memories involves plasticity of the thalamic and cortical pathways to the lateral amygdala (LA). The maintenance of synaptic plasticity requires the interplay between input-specific synaptic tags and the allocation of plasticity-related proteins (PRPs). Based on this interplay, weakly activated synapses can express long-lasting synaptic plasticity by cooperation with strongly activated ones. Increasing the number of activated synapses can shift cooperation to competition. Synaptic cooperation and competition can determine whether two events, separated in time, are linked or selected. The rules that determine whether synapses cooperate or compete are unknown. We found that synaptic cooperation and competition, in the LA, are determined by the temporal sequence of cortical and thalamic stimulation and that the strength of the synaptic tag is modulated by the endocannabinoid signalling. This modulation is particularly effective in thalamic synapses, suggesting a critical role of endocannabinoids in restricting thalamic plasticity. Also, we found that PRPs availability is modulated by the action-potential firing of neurons, shifting competition to cooperation. Our data present the first evidence that pre-synaptic modulation of synaptic activation, by the cannabinoid signalling, function as a temporal gating mechanism limiting synaptic cooperation and competition.