Hierarchical Order of Coexisting Pre- and Postsynaptic Forms of Long-Term-Potentiation at Synapses in Amygdala

Synaptic rules that may determine the interaction between coexisting forms of long-term potentiation (LTP) at glutamatergic central synapses remain unknown. Here, we show that two mechanistically distinct forms of LTP could be induced in the thalamic inputs to the lateral nucleus of the amygdala (LA) with an identical presynaptic membrane polarization. One form of LTP, resulting from pairing of postsynaptic depolarization and low-frequencey presynaptic stimulation, was both induced and expressed postsynaptically ("post-LTP"). The same stimulation in the abcence of postsynaptic depolarization led to LTP, which was induced and expressed presynaptoically ("pre-LTP"). The inducibility of coexisting pre- and postsynaptic forms of LTP at synapses in thalamic input followed a well-defined hierarchical order, such that pre-LTP was suppressed when post-LTP was induced. The interaction was mediated by activation of cannbinoid type 1 receptors by endogenous cannabinoids released in the lateral nucleus of the amygdala in response to activation of the type 1 metabotropic glutamate recepotr. These results suggest a previously unknown mechanism by which the hierarchy of coexisting forms of long-term synaptic plasticity in the neural circuits of learned fear could be established, possibly reflecting the hierarchy of memories for the previously experienced fearful events according to their aversiveness level