Trace conditioning and the hippocampus: the importance of contiguity

Abstract

Trace conditioning, a form of classical conditioning in which the presentation of the conditioned stimulus (CS) and the unconditioned stimulus (US) is separated in time by an interstimulus interval, requires an intact hippocampus. In contrast, classical conditioning procedures in which the CS and US are not separated by an interstimulus interval (i.e., delay conditioning procedures) typically do not (Solomon et al., 1986). However, why trace conditioning is dependent on the hippocampus is unknown. Several theories suggest that it is specifically the discontiguity between the CS and US in trace conditioning that critically engages the hippocampus. However, there are other explanations that do not depend on discontiguity. To determine whether the lack of contiguity renders trace conditioning hippocampal dependent, we designed a "contiguous trace conditioning" (CTC) paradigm in which CS-US contiguity is restored by re-presenting the CS simultaneously with the US. Although rats with excitotoxic lesions of the hippocampus could not learn a standard trace fear-conditioning paradigm, lesioned rats trained on CTC showed significant conditioning, at levels similar to those with sham surgeries. Importantly, lesioned rats trained solely with simultaneous CS-US presentations did not demonstrate conditioning. Together, these data suggest that rats with hippocampal lesions can form a memory of a trace CS-US association when contiguity is restored. Therefore, the dependence of traditional trace paradigms on the hippocampus can be attributed to the absence of temporal contiguity.

Figure 1.

Subjects in the experimental group were given excitotoxic lesions of the complete hippocampus. A, Representative photomicrograph of tissue from a sham-operated control (left column) and hippocampal-lesioned rat (right column). Substantial cell loss was observed throughout the dorsal and ventral hippocampus. B, The drawing depicts the largest (in gray) and smallest (in black) lesion selected from all subjects included in the study, shown here according to the atlas of Paxinos and Watson (1997).

Figure 2.

Hippocampal-lesioned subjects were able to form a memory of the trace relationship when trained with the CTC procedure but not when trained with trace conditioning. A, This schematic represents the temporal relationship between the CS and US for a single trial for the following four conditioning procedures: trace, CTC, simultaneous, and delay conditioning. B, The percentage of change in movement from the baseline was calculated to quantify conditioned fear to the CS during testing. Rats with hippocampal lesions that were trained with delay conditioning showed conditioned responding, which indicates that the lesions did not disrupt conditioning on tasks that do not require the hippocampus. Unlike sham-operated controls, rats with hippocampal lesions trained with trace conditioning did not show conditioned responding. However, rats with hippocampal lesions trained with the CTC procedure showed significant responding at levels similar to their sham-operated counterparts. Because lesioned subjects trained with simultaneous conditioning alone did not emit conditioned responses, the responding expressed by subjects in the CTC lesion group cannot be attributed to the simultaneous component of the training procedure. Together, these results suggest that rats with lesions of the hippocampus can form a memory of the CS–US association if they are trained with CTC, in which contiguity is restored. Error bars indicate SEM.