The small GTPase RhoA, but not Rac1, is essential for conditioned aversive memory formation through regulation of actin rearrangements in rat dorsal hippocampus

Abstract

Aim: Actin rearrangements are induced in the dorsal hippocampus after conditioned morphine withdrawal, and involved in the formation of conditioned place aversion. In the present study, we investigated the mechanisms underlying the actin rearrangements in rat dorsal hippocampus induced by conditioned morphine withdrawal. Methods: The RhoA-ROCK pathway inhibitor Y27632 (8.56 μg/1 μL per side) or the Rac1 inhibitor NSC23766 (25 μg/1 μL per side) was microinjected into the dorsal hippocampus of rats. Conditioned place aversion (CPA) induced by naloxone-precipitated morphine withdrawal was assessed. Crude synaptosomal fraction of hippocampus was prepared, and the amount of F-actin and G-actin was measured with an Actin Polymerization Assay Kit. Results: Conditioned morphine withdrawal significantly increased actin polymerization in the dorsal hippocampus at 1 h following the naloxone injection. Preconditioning with microinjection of Y27632, but not NSC23766, attenuated CPA, and blocked the increase in actin polymerization in the dorsal hippocampus. Conclusion: Our results suggest that the small GTPase RhoA, but not Rac1, in the dorsal hippocampus is responsible for CPA formation, mainly through its regulation of actin rearrangements.

Social Isolation Induces Rac1-Dependent Forgetting of Social Memory

“…In fact, using dominant mutant-expressing approaches, it was shown that Rac1, but not RhoA, mediates forgetting in Drosophila (Shuai et al, 2010). In addition, pharmacological studies showed that memory formation and LTP initiation are regulated by RhoA, but not Rac1, activity in mammalians (Rex et al, 2009;Wang et al, 2013), whereas Rac1 was reported to regulate LTP stabilization and memory maintenance in previous (Liu et al, 2016;Rex et al, 2009) and current studies, suggesting Rac1 and RhoA may play distinct roles in regulating memory processes.…”

Morphine-Associated Contextual Cues Induce Structural Plasticity in Hippocampal CA1 Pyramidal Neurons

“…To visually enhance virally delivered YFP expression, we completed immunohistochemical analysis in 200 μm coronal brain slices with chicken anti-GFP (primary antibody, Aves Labs, Tigard, OR) and anti-chicken 488 (secondary antibody, Molecular Probes, Eugene, OR). Staining for GFP served as a method to increase the brightness of the viral YFP in order to easily image small sub-micron dendritic spines, a method that has been used by others (Wang et al, 2013a). To qualify for spine analysis, dendritic segments had to satisfy the following requirements: (i) the segment had to be completely filled (all endings were excluded) and (ii) segment must be at least 50 μm from the soma.…”

Formation of aversive memories associated with conditioned drug withdrawal requires BDNF expression in the amygdala in acute morphine-dependent rats

“…When the animals are re-exposed to the apparatus, they exhibit significant aversive motivation. Therefore, the CPA model is a very sensitive method for measuring the aversive motivation in drug withdrawal [11][12][13] . Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family of growth factors, regulates neuron synaptic plasticity and is an important mediator of the induction of LTP; thus, BDNF plays a vital role in learning and memory in multiple brain areas [14][15][16][17][18] .…”