Characterizing cognitive aging of associative memory in animal models

Abstract

An overview is provided of the simple single-cue delay and trace eyeblink conditioning paradigms as techniques to assess associative learning and memory in the aged. We highlight and focus this review on the optimization of the parameter space of eyeblink conditioning designs in the aged to avoid and control for potential confounds that may arise when studying aged mammals. The need to examine the contribution of non-associative factors that can contribute to performance outcomes is emphasized, and how age-related changes in the central nervous system as well as peripheral sensory factors can potentially bias the interpretation of the data in the aged is discussed. The way in which slight alterations of the parameter space in the delay and trace eyeblink conditioning paradigms can lead to delayed but intact conditioning, rather than impaired performance in aged animals is also discussed. Overall, the eyeblink conditioning paradigm, when optimized for the age of the animal in the study, is an elegantly simple technique for assessment of associative learning and memory. When design caveats described above are taken into account, this important type of memory, with its well-defined neural substrates, should definitely be included in cognitive assessment batteries for the aged.

Keywords: associative learning; cognitive assessment battery; delay conditioning; optimization; trace conditioning.

Figure 1

Diagram of the temporal relationship in the Delay (A) and Trace (B) eyeblink conditioning paradigms. The main difference between the delay and trace conditioning is that the CS and US do not overlap in the trace conditioning paradigm. The duration of the CS in the delay paradigm can vary in time. The duration of the CS and the trace interval in the trace paradigm can also vary in time. The optimal duration of the CS and the trace interval in the delay and trace paradigm is species-specific.

Figure 2

Behavioral audiograms (solid lines) for the domestic mouse, Norway rat, rabbit, and human. Audigram based upon eyeblink conditioning (dashed line) in the rabbit. The frequency of the auditory CS used across the majority of eyeblink conditioning studies is marked (asterisks). However, the importance of optimizing the auditory stimulus for each species is highlighted in studies in mice where the CS that has been used is near the bottom of the audible range for this species. Audiograms derived from: the domestic mouse (Koay et al., 2002), the Norway rat (Heffner et al., 1994), the rabbit (Heffner and Masterton, ; Martin et al., 1980), and the human (Kojima, ; Jackson et al., 1999).