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.

Several regions in the rat brain contain neurons known as head-direction cells, which fire only when the rat's head is facing in a specific direction. Head-direction cells are influenced only by the direction of the head with respect to the static environmental surroundings, and not by the position of the head relative to the body. Each head-direction cell has its own preferred direction of firing, so that together, the population of cells provides a continuous signal of momentary directional heading. Here, head-direction cells were recorded from the post-subicular cortex (PSC) and anterodorsal nucleus (ADN) of the thalamus of freely moving rats. Cell activity was analyzed in relation to both momentary head direction, and the angular velocity of head turns. Head-direction cells in PSC maintained the same directional firing preference, regardless of the angular head velocity. By contrast, head-direction cells in ADN systematically shifted their directional firing preference, as a function of angular head velocity. The ADN cells always shifted their directional tuning peak to the left during clockwise head turns, and to the right during counterclockwise head turns. These results suggest that ADN neurons anticipate the future direction of the head, whereas PSC neurons encode the present direction of the head. Based on these findings, we hypothesize that neurons in PSC and ADN are reciprocally connected to form a thalamocortical circuit, which computes the directional position of the rat's head by integrating the angular motion of the head over time.

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We recorded neurons from the hippocampus of freely behaving rats during an auditory fear conditioning task. Rats received either paired or unpaired presentations of an auditory conditioned stimulus (CS) and an electric shock unconditioned stimulus (US). Hippocampal neurons (place and theta cells) acquired responses to the auditory CS in the paired but not in the unpaired group. After CS-US pairing, rhythmic firing of theta cells became synchronized to the onset of the CS. Conditioned responses of place cells were gated by their location-specific firing, so that after CS-US pairing, place cells responded to the CS only when the rat was within the cell's place field. These findings may help to elucidate how the hippocampus contributes to context-specific memory formation during associative learning.