Interrogating rodents regarding their object and spatial memory Robert E Clark 1 and Stephen J Martin 2 Today, neuroscientists have access to a host of advanced techniques — ranging from targeted genetic interventions to brain imaging — that are rapidly providing new insights. Ultimately, however, memory must be inferred from its behavioral read-out. Thus, to fully utilize the advanced technologies available today, we must select the most appropriate behavioral procedures from those currently available, or else devise novel behavioral techniques to meet a specific demand. If we merely use standard tests of memory in a non-optimal way, we risk collecting incomplete information and reaching erroneous conclusions. Relevant to these issues, there have been substantial developments in the methods used to evaluate two of the most frequently studied forms of memory in the rodent — recognition memory and spatial memory. Addresses 1 Department of Psychiatry, 0603 University of California San Diego and Veterans Affairs Medical Center, San Diego, La Jolla, CA 92093, USA 2 Laboratory for Cognitive Neuroscience, Division of Neuroscience, University of Edinburgh, 1 George Square, Edinburgh, EH8 9JZ, UK Corresponding author: Clark, Robert E (reclark@ucsd.edu) Current Opinion in Neurobiology 2005, 15:593–598 This review comes from a themed issue on New technologies Edited by Gero Miesenbo ¨ ck and Richard GM Morris 0959-4388/$ – see front matter # 2005 Elsevier Ltd. All rights reserved. DOI 10.1016/j.conb.2005.08.014 Introduction Declarative memory supports the recollection of facts and events and the encoding of memories in terms of relationships among the elements being learned. The stored representations are flexible and can guide suc- cessful performance under a wide range of test condi- tions. Recognition memory refers to the capacity to identify a previously encountered item and spatial mem- ory refers to the ability to remember a place. Recogni- tion and spatial memory are both forms of declarative memory in humans and are two of the most widely studied examples of memory in rodents. Here, we review recent advances in two behavioral paradigms that have become benchmark tests for these forms of mem- ory in rodents. Recognition memory: have you seen this before? Early work on recognition memory was conducted in the monkey [1] using, what for many years was regarded as the benchmark test of visual recognition memory, the delayed nonmatching to sample task (DNMS). In this task, the animal must displace an object to receive a food reward (sample phase). Following a delay, the object from the sample phase is presented with a novel object and the animal receives a food reward for displacing the novel object (choice phase). This task and the subsequent development of analogous versions for the rat [2,3  ] have been enormously productive in identifying the specific structures that are important for recognition memory [4]. However, during the past few years, DNMS has largely been supplanted by the novel object recognition (NOR) task (also referred to as ‘spontaneous object recognition’ or ‘visual paired-comparison’). Novel object recognition NOR consists of familiarization, delay and test phases, and rats’ spontaneous preference for novelty provides the index of memory (Figure 1). The NOR task was originally designed to measure memory in preverbal human infants (e.g. [5]), and has been adapted for use in the monkey [6] and rodent [7,8]. Work in humans indicates that perfor- mance depends on the subject’s voluntary search of the environment, and is guided by what is recognized as familiar or novel. In this sense the task provides a measure of declarative, or declarative-like, memory [9]. This task has several advantages over other tests of recognition memory such as DNMS. One of the most obvious is that NOR exploits the subject’s innate pre- ference for novelty, and, thus, does not require explicit rule learning. This is a logistical advantage in that the task does not require extensive pre-training to teach the sub- ject the nonmatching rule. Furthermore, the inherent variability introduced during rule acquisition is avoided. There is also good evidence that the NOR task is more sensitive to recognition memory impairments than DNMS [10  ,11  ]. Finally, the NOR task can be adminis- tered to humans, monkeys, rats and mice in essentially the same way (humans and monkeys typically view 2-D pictures and rodents are allowed to explore 3-D objects), and the behavioral findings have been remarkably con- sistent across species. For example, when the delay between the familiarization and test phase is short (i.e. when memory is strongest) humans, monkeys, rats and mice tend to explore the novel stimulus approximately twice as much as the familiar stimulus, and damage that www.sciencedirect.com Current Opinion in Neurobiology 2005, 15:593–598