Inhibition of Rac1 in ventral hippocampal excitatory neurons improves social recognition memory and synaptic plasticity

Abstract

Rac1 is critically involved in the regulation of the actin cytoskeleton, neuronal structure, synaptic plasticity, and memory. Rac1 overactivation is reported in human patients and animal models of Alzheimer’s disease (AD) and contributes to their spatial memory deficits, but whether Rac1 dysregulation is also important in other forms of memory deficits is unknown. In addition, the cell types and synaptic mechanisms involved remain unclear. In this study, we used local injections of AAV virus containing a dominant-negative (DN) Rac1 under the control of CaMKIIα promoter and found that the reduction of Rac1 hyperactivity in ventral hippocampal excitatory neurons improves social recognition memory in APP/PS1 mice. Expression of DN Rac1 also improves long-term potentiation, a key synaptic mechanism for memory formation. Our results suggest that overactivation of Rac1 in hippocampal excitatory neurons contributes to social memory deficits in APP/PS1 mice and that manipulating Rac1 activity may provide a potential therapeutic strategy to treat social deficits in AD.

Roles of Rac1-Dependent Intrinsic Forgetting in Memory-Related Brain Disorders: Demon or Angel

“…The manipulation of hippocampal Rac1 activity using adeno-associated viruses (AAVs) carrying dominant-negative Rac1 increases the retention of object recognition-induced memory that commonly lasts less than 72 h, while elevated Rac1 activity using AAVs carrying constitutively active Rac1 accelerates memory decay to less than 24 h [ 20 ]. Social recognition memory, contextual fear memory, and cocaine-associated memory performance also show a similar pattern to that produced by the aforementioned research through viral-mediated regulation strategies of Rac1 activity [ 22 , 23 , 150 , 151 , 152 ].…”