Abstract
Rac1, a member of the Rho family of small GTPases, is crucial for morphological changes of the mature neuronal synapse including spine formation and activity-dependent spine enlargement, while its role in the formation of associated memories, such as conditioned fear memory, is not clear. Here, we report that selective deletion of Rac1 in excitatory neurons, but not in parvalbumin inhibitory neurons, impaired short- and long-term memories (STM and LTM) of fear conditioning. Conditional knockout of Rac1 before associative fear training in the basolateral amygdala (BLA), a key area for fear memory acquisition and storage, impaired fear memory. The expression of dominant-negative mutant of Rac1, or infusion of Rac1 inhibitor NSC23766 into BLA blocked both STM and LTM of fear conditioning. Furthermore, selective inhibition of Rac1 activation in BLA immediately following fear conditioning impaired STM and LTM, demonstrating that fear conditioning-induced Rac1 activation in BLA plays a critical role in the formation of both STM and LTM of conditioned fear.
Highlights
Fear conditioning is a classic model of associative fear learning, which is critical for animals to trigger adaptive behaviors in response to dangerous environmental threats
These results suggest that related C3 botulinum toxin substrate 1 (Rac1) in excitatory neurons is required for short-term memory (STM) and long term memory (LTM) of conditioned fear
We found that loss of Rac1 in excitatory neurons impaired STM and LTM of fear memory, and the ablation of Rac1 in basolateral amygdala (BLA), a key brain region for auditory fear memory with abundant glutamatergic neurons, impaired the formation of STM and LTM
Summary
Fear conditioning is a classic model of associative fear learning, which is critical for animals to trigger adaptive behaviors in response to dangerous environmental threats. In a typical fear conditioning protocol, the animals are exposed to a neutral conditioned stimulus (CS), such as tone or the context of the conditioning chamber, paired with an aversive unconditioned stimulus (US), such as an electric footshock. After this CS-US association learning, the CS could elicit a set of defensive responses, such as freezing (Kim and Jung, 2006). Blockade of the NR2B subunit of the NMDAR in the amygdala before fear conditioning impairs the formation of STM and LTM (Rodrigues et al, 2001). Infusion of actin cytoskeleton assembly inhibitors into the amygdala immediately before fear conditioning interferes with the formation of LTM (Fischer et al, 2004; Mantzur et al, 2009)
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