
Abstract
The lateral amygdala (LA) has been proposed as a critical site for fear memory storage and, long-term potentiation (LTP) at LA synapses induced by fear conditioning has been thought to be the cellular mechanism underlying fear memory formation. However, similar synaptic changes are also observed in upstream areas, such as the medial geniculate nucleus (MGN) and auditory cortex (AC), raising the critical question of where the fear memory is actually formed and stored. Here we used optogenetic approach to determine if direct stimulation of the presynaptic auditory projections in the LA can serve as a conditioned stimulus (CS) that, when paired with a foot shock unconditioned stimulus (US), can drive fear conditioning. Mice were injected with AAV-ChR2 in the two main auditory pathways to LA, MGN and AC, sending auditory information into the LA during auditory fear conditioning. Optical photostimulation was used to activate ChR2-expressing presynaptic axons in the LA as a CS for fear conditioning. 24 hours later, the same optogenetic CS produced robust freezing responses while control mice injected with AAV-GFP did not. In parallel, we also examined LTP induction in LA slices with ChR2 expression in MGN and AC projections to LA neurons. Whole-cell patch recording showed that pairing photo-stimulation (3 Hz) of auditory projections in LA with postsynaptic current injection produced strong LTP at LA synapses. Our data provide compelling evidence that fear memory can be formed in the LA synapses independent of the activity of upstream areas delivering auditory information and LTP at the LA synapses may underlie fear memory formation.