Homeostatic switch in hebbian plasticity and fear learning after sustained loss of Cav1.2 calcium channels.
Ca(2+) influx through postsynaptic Ca(v)1.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 Ca(v)1.2 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 Ca(v)1.2 triggers a homeostatic change of the synapse, leading to a fundamental alteration of the mechanism of Hebbian plasticity by synaptic incorporation of Ca(2+)-permeable, GluA2-lacking AMPA receptors. Our results demonstrate for the first time the importance of the Ca(v)1.2 LTCC subtype in synaptic plasticity and fear memory acquisition.
Langwieser
Nicole
N
Institute for Pharmacology, Technical University Munich, 80802 Munich, Germany.
Christel
Carl J
CJ
Kleppisch
Thomas
T
Hofmann
Franz
F
Wotjak
Carsten T
CT
Moosmang
Sven
S
D000679:Amygdala / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D020746:Calcium Channels, L-Type / Q000502:physiology*; D003214:Conditioning, Classical / Q000502:physiology*; D004594:Electrophysiology; D005239:Fear / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology; D017403:In Situ Hybridization; D017774:Long-Term Potentiation / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009434:Neural Pathways / Q000502:physiology; D009474:Neurons / Q000502:physiology; D018091:Receptors, AMPA / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D016622:Silver Staining; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology; D013788:Thalamus / Q000502:physiology*; D014741:Video Recording
C514350:CACNA1C protein, mouse; D020746:Calcium Channels, L-Type; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate