Homeostatic switch in Hebbian plasticity and fear learning after sustained loss of Cav1.2 calcium channels

Abstract

Ca2+ influx through postsynaptic Cav1.x L-type voltage-gated channels (LTCCs) is particularly effective in activating neuronal biochemical signaling pathways that might be involved in Hebbian synaptic plasticity (i.e., long-term potentiation and depression) and learning and memory. Here, we demonstrate that Cav1.2 is the functionally relevant LTCC isoform in the thalamus-amygdala pathway of mice. We further show that acute pharmacological block of LTCCs abolishes Hebbian plasticity in the thalamus-amygdala pathway and impairs the acquisition of conditioned fear. On the other hand, chronic genetic loss of Cav1.2 triggers a homeostatic change of the synapse, leading to a fundamental alteration of the mechanism of Hebbian plasticity by synaptic incorporation of Ca2+-permeable, GluA2-lacking AMPA receptors. Our results demonstrate for the first time the importance of the Cav1.2 LTCC subtype in synaptic plasticity and fear memory acquisition. Copyright © 2010 the authors.