Bilateral phosphorylation of ERK in the lateral and centrolateral amygdala during unilateral storage of fear memories.

We previously showed that when rats were trained to fear an auditory conditioned stimulus (CS) by pairing it with a mild unilateral shock to the eyelid (the unconditioned stimulus, or US), conditioned freezing depended upon the amygdala contralateral but not ipsilateral from the US. It was proposed that convergent activation of amygdala neurons by the CS and US occurred mainly in the amygdala contralateral from US delivery, causing memories of the CS-US association to be stored primarily by that hemisphere. In the present study, we further tested this interpretation by administering unilateral infusions of U0126 (in 50% dimethyl sulfoxide (DMSO) vehicle) to block phosphorylation of extracellular signal-responsive kinase (ERK) in the amygdala prior to CS-US pairings. Conditioned freezing was impaired 24 h after training when U0126 was infused contralaterally-but not ipsilaterally-from the US, suggesting that fear memories were consolidated mainly by the contralateral amygdala. However, immunostaining experiments revealed that ERK phosphorylation was elevated in both hemispheres of the amygdale's lateral (LA) and centrolateral (CeL) nuclei after paired (but not unpaired (UNP)) presentations of the CS and US. Thus, fear acquisition induced ERK phosphorylation bilaterally in the amygdala, even though the ipsilateral hemisphere did not appear to participate in conditioned freezing. These findings suggest that associative plasticity may occur in both amygdala hemispheres even when only one hemisphere is involved in freezing behavior. Conditioning-induced ERK phosphorylation was identical in both hemispheres of LA, but was slightly greater in the contralateral than ipsilateral hemisphere of CeL. Hence, asymmetric induction of plasticity in CeL might help to explain why conditioned freezing depends preferentially upon the amygdala contralateral from the US in our fear conditioning paradigm.