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Séminaire impromptu - Rosalina Fonseca Role of the endocannabinoids in amygdala synaptic cooperation and competition

Abstract :

 The synaptic-capture hypothesis of memory allows weak events, only capable of inducing transient, short-term memories, to be consolidated into long-term memories if occurring in the context of other strong events.
Memory cooperation is presumably achieved by the sharing of a common pool of plasticity-related proteins (PRPs) that are captured by synaptic tags, set at activated synapses. Interestingly, memories can also compete, interfering with each other. What are the rules that determine whether memories cooperate or compete? To tackle this question, we have studied the interaction between the cortical and thalamic afferents to projection neurons of the lateral amygdala (LA), a circuitry necessary for the formation of fear memories. We found that cortical synapses can cooperate with thalamic synapses, even within an extended time window of 30 minutes. Thalamic-cortical cooperation is dependent on the sharing of PRPs between the two groups of activated synapses and results in the re-enforcement of both inputs in an associative manner. Interestingly, synaptic cooperation between the cortical and thalamic synapses is bi-directional but temporally asymmetrical. The time window of thalamic cooperation is limited by the activation of the endocannabinoid receptor 1 (CB1R). Thalamic and cortical synapses also compete for the availability of PRPs. The stimulation of an additional thalamic projection leads to an unbalance between the number of activated synapses and PRPs availability, leading to competition. Synaptic competition is also modulated by time: extending the time window of the second thalamic stimulation to 30 minutes, decreases synaptic competition. As for cooperation, CB1R activation also restricts synaptic competition. Since CB1R activation is involved in discriminative learning, it is conceivable that by limiting cortical-to-thalamic cooperation, the endocannabinoid signalling limits generalization. Our results show that cortical and thalamic inputs to the LA can cooperate and compete at large time intervals, allowing a continuous integration of information at amygdala synapses.