Rac1 GTPase activation impairs fear conditioning-induced structural changes in basolateral amygdala neurons and long-term fear memory formation.

Long-term memory formation leads to enduring alterations in synaptic efficacy and neuronal responses that may be created by changes in neuronal morphology. We show that fear conditioning leads to a long-lasting increase in the volume of the primary and secondary dendritic branches, but not of distal branches, of neurons located at the basolateral amygdala (BLA). The length of the dendritic branches is not affected by fear conditioning. Fear conditioning leads to an enduring increase in the length and volume of dendritic spines, especially in the length of the spine neck and the volume of the spine head. Fear conditioning does not affect dendritic spine density. We further reveal that activation of Rac1 in BLA during fear conditioning impairs long-term auditory, but not contextual, fear conditioning memory. Activation of Rac1 during fear conditioning prevents the enduring increase in the dendritic primary branch volume and dendritic spines length and volume. Rac1 activation per se has no effect on neuronal morphology. These results show that fear conditioning induces changes known to reduce the inhibition of signal propagation along the dendrite and the increase in synaptic efficacy whereas preventing these changes, by Rac1 activation, impairs fear memory formation.

The Role of Rac GTPase in Dendritic Spine Morphogenesis and Memory.

The ability to form memories in the brain is needed for daily functions, and its impairment is associated with human mental disorders. Evidence indicates that long-term memory (LTM)-related processes such as its consolidation, extinction and forgetting involve changes of synaptic efficacy produced by alterations in neural transmission and morphology. Modulation of the morphology and number of dendritic spines has been proposed to contribute to changes in neuronal transmission mediating such LTM-related processes. Rac GTPase activity is regulated by synaptic activation and it can affect spine morphology by controlling actin-regulatory proteins. Recent evidence shows that changes in Rac GTPase activity affect memory consolidation, extinction, erasure and forgetting and can affect spine morphology in brain areas that mediate these behaviors. Altered Rac GTPase activity is associated with abnormal spine morphology and brain disorders. By affecting Rac GTPase activity we can further understand the roles of spine morphogenesis in memory. Moreover, manipulation of Rac GTPase activity may serve as a therapeutic tool for the treatment of memory-related brain diseases.