Methamphetamine Learning Induces Persistent and Selective Nonmuscle Myosin II-Dependent Spine Motility in the Basolateral Amygdala.

Nonmuscle myosin II inhibition (NMIIi) in the basolateral amygdala (BLA), but not dorsal hippocampus (CA1), selectively disrupts memories associated with methamphetamine (METH) days after learning, without retrieval. However, the molecular mechanisms underlying this selective vulnerability remain poorly understood. A known function of NMII is to transiently activate synaptic actin dynamics with learning. Therefore, we hypothesized that METH-associated learning perpetuates NMII-driven actin dynamics in synapses, leading to an extended window of vulnerability for memory disruption. We used time-lapse two-photon imaging of dendritic spine motility in acutely prepared brain slices from female and male mice following METH-associated learning as a readout of actin-myosin dynamics. Spine motility was persistently increased in the BLA, but not in CA1. Consistent with the memory disrupting effect of intra-BLA NMII inhibition, METH-induced changes to BLA spine dynamics were reversed by a single systemic injection of an NMII inhibitor. Intra-CA1 NMII inhibition, on the other hand, did not disrupt METH-associated memory. Thus, we report identification of a previously unknown ability for spine actin dynamics to persist days after stimulation and that this is under the control of NMII. Further, these perpetual NMII-driven spine actin dynamics in BLA neurons may contribute to the unique susceptibility of METH-associated memories.