The hippocampus is believed to be an important structure for learning tasks that require temporal processing of information. The trace classical conditioning paradigm requires temporal processing because the conditioned stimulus (CS) and the unconditioned stimulus (US) are temporally separated by an empty trace interval. The present study sought to determine whether the hippocampus was necessary for rats to perform a classical trace fear conditioning task in which each of 10 trials consisted of an auditory tone CS (15‐s duration) followed by an empty 30‐s trace interval and then a fear‐producing floor‐shock US (0.5‐s duration). Several weeks prior to training, animals were anesthetized and given aspiration lesions of the neocortex (NEO; n = 6), hippocampus and overlying neocortex (HIPP; n = 7), or no lesions at all (control; n = 6). Approximately 24 h after trace conditioning, NEO and control animals showed a significant decrease in movement to a CS‐alone presentation that was indicative of a conditioned fear response. Animals in the HIPP group did not show conditioned fear responses to the CS alone, nor did a pseudoconditioning group (n = 7) that was trained with unpaired CSs and USs. Furthermore, all groups except the HIPP group showed conditioned fear responses to the original context in which they received shock USs. One week later, HIPP, NEO, and control animals received delay fear‐conditioning trials with no trace interval separating the CS and US. Six of seven HIPP animals could perform the delay version, but none could perform the trace version. This result suggests that the trace fear task is a reliable and useful model for examining the neural mechanisms of hippocampally dependent learning. Hippocampus 1998;8:638–646. © 1998 Wiley‐Liss, Inc.

Previous studies have implicated 2 cortical regions interconnected with the hippocampal formation, the retrosplenial cortex (RSC) and the medial prefrontal cortex (mPFC), as loci important for the acquisition of hippocampally dependent trace eyeblink conditioning. These loci have also been proposed to serve as long-term storage sites of task critical information. This study used lesions made prior to training to investigate the roles of the RSC, as well as the caudal and rostral subdivisions of the mPFC, in the acquisition and subsequent extinction of trace eyeblink conditioning in the rabbit. The caudal mPFC and rostral mPFC were shown to be critical for acquisition and extinction of the conditioned reflex, respectively. The data indicate that the RSC is not critical for acquisition or extinction of the trace conditioned reflex.

The sequence of changes in single neuron activity in the CA1 area of the rabbit hippocampus was examined during daily sessions (80 trials/session) of hippocampally dependent nonspatial trace eyeblink (i.e., nictitating membrane response) conditioning. Each trial for trace conditioned animals (n = 7) consisted of a tone conditioned stimulus (CS; 6 kHz; 90 dB, 100 ms) followed by a 500-ms silent trace period, then a corneal airpuff unconditioned stimulus (US; 3.0 psi; 150 ms). Control animals (n = 5) received unpaired CSs and USs. Most pyramidal (n = 309) and theta (n = 21) cells were recorded for a single day of training. The activity of cells for each animal were grouped according to: the day of training that CRs began to increase and the day of training that CR performance became asymptotic. Pyramidal cells from trace conditioned animals demonstrated several stages of learning-related activity: large increases in activity after both the CS and US early in conditioning on the day of training when CRs began to increase, smaller moderate increases in activity on the following days of training, and decreases in activity after the US during asymptotic CRs. Pyramidal cell-increases declined significantly across the trials of each daily session. Theta cells showed an activity pattern opposite to the pyramidal cells, consistent with the notion that theta cells have an inhibitory influence on pyramidal cells. Single pyramidal cells also were categorized into response profiles. Most pyramidal response profiles showed increases in activity specific to the day of initial CRs. Two of the pyramidal response profiles may be involved in assessing the temporal properties of the CS-US trace conditioning trial.

Trace fear conditioning is a learning task that requires the association of an auditory conditioned stimulus (CS) and a shock unconditioned stimulus (US) that are separated by a 20-s trace interval. Single neuron activity was recorded from the prelimbic and infralimbic areas of the medial prefrontal cortex in rats during trace fear conditioning or nonassociative unpaired training. Prelimbic neurons showed learning-related increases in activity to the CS and US, whereas infralimbic neurons showed learning-related decreases in activity to these stimuli. A subset of prelimbic neurons exhibited sustained increases in activity during the trace interval. These sustained prelimbic responses may provide a bridging code that allows for overlapping representations of CS and US information within the trace fear conditioning circuit.