Synaptic plasticity in the lateral amygdala: a cellular hypothesis of fear conditioning.
Fear conditioning is a form of associative learning in which subjects come to express defense responses to a neutral conditioned stimulus (CS) that is paired with an aversive unconditioned stimulus (US). Considerable evidence suggests that critical neural changes mediating the CS-US association occur in the lateral nucleus of the amygdala (LA). Further, recent studies show that associative long-term potentiation (LTP) occurs in pathways that transmit the CS to LA, and that drugs that interfere with this LTP also disrupt behavioral fear conditioning when infused into the LA, suggesting that associative LTP in LA might be a mechanism for storing memories of the CS-US association. Here, we develop a detailed cellular hypothesis to explain how neural responses to the CS and US in LA could induce LTP-like changes that store memories during fear conditioning. Specifically, we propose that the CS evokes EPSPs at sensory input synapses onto LA pyramidal neurons, and that the US strongly depolarizes these same LA neurons. This depolarization, in turn, causes calcium influx through NMDA receptors (NMDARs) and also causes the LA neuron to fire action potentials. The action potentials then back-propagate into the dendrites, where they collide with CS-evoked EPSPs, resulting in calcium entry through voltage-gated calcium channels (VGCCs). Although calcium entry through NMDARs is sufficient to induce synaptic changes that support short-term fear memory, calcium entry through both NMDARs and VGCCs is required to initiate the molecular processes that consolidate synaptic changes into a long-term memory.
Blair
H T
HT
Center for Neural Science, New York University, New York, New York 10003, USA.
Schafe
G E
GE
Bauer
E P
EP
Rodrigues
S M
SM
LeDoux
J E
JE
D000679:Amygdala / Q000502:physiology*; D000818:Animals; D001245:Association Learning; D003213:Conditioning, Psychological; D005239:Fear / Q000523:psychology*; D006801:Humans; D009473:Neuronal Plasticity / Q000502:physiology*; D013569:Synapses / Q000502:physiology*