Hippocampal Damage and Anterograde Object-Recognition in Rats After Long Retention Intervals Dave G. Mumby,* Annie Tremblay, Valerie Lecluse, and Hugo Lehmann ABSTRACT: Although several studies in rats have found that hippo- campal damage has negligible effects on anterograde object-recognition memory, the findings are not entirely conclusive, because most studies have used retention intervals lasting only a few hours. We assessed the effects of neurotoxic hippocampal lesions on anterograde object recog- nition, using a novel-object preference test, with retention intervals that were considerably longer than in previous studies—24 h, 1 week, and 3 weeks. To promote object recognition after such long intervals, rats were familiarized with a sample object in an open field for 5 min/day for 5 consecutive days. Recognition was assessed by comparing the amount of time spent investigating the sample versus a novel object on a preference test at one of the postlearning intervals. The rats with hip- pocampal lesions displayed a normal novelty preference after a 3-week interval, and their performance across the three delay conditions was not significantly different from that of control rats. The findings indicate that extensive hippocampal damage spares anterograde object recognition in rats, even after retention intervals lasting days or weeks. V V C 2005 Wiley-Liss, Inc. KEY WORDS: nonspatial memory; object recognition; novelty prefer- ence; exploratory behavior; open field INTRODUCTION Object-recognition memory is the ability to discriminate between objects that have been previously encountered and objects that have not. This ability tends to be impaired in amnesic patients with damage to temporal-lobe structures, which typically includes the hippocampus (HPC) and various parahippocampal structures. The effects of damage restricted to the HPC on anterograde object-recognition memory have been the focus of much debate over the past few decades. During the 1970s and 1980s, several studies suggested that damage to the HPC, either alone or in combination with damage to other medial-temporal- lobe structures, impairs anterograde object recognition in monkeys (Gaffan, 1974; Bachevalier et al., 1985; Zola-Morgan and Squire, 1985, 1986; Murray and Mishkin, 1986; Bachevalier and Mishkin, 1989). It has since become clear, however, that the capacity for restricted HPC damage to produce significant anterograde recognition deficits had been overestimated, and it is now widely accepted that damage to parahippo- campal regions, most notably the perirhinal cortex, can produce more severe impairments of visual recog- nition memory than HPC damage, both in rats (Mumby and Pinel, 1994; Wiig and Bilkey, 1995; Aggleton et al., 1997; Aggleton and Brown, 1999) and in monkeys (Zola-Morgan et al., 1989; Gaffan and Murray, 1992; Meunier et al., 1993; Murray, 1996). There is also evidence that anterograde recog- nition memory is largely spared in some amnesic patients with significant HPC damage (Aggleton and Shaw, 1996; cf. Manns and Squire, 1999). The finding of preserved anterograde recognition memory after extensive HPC damage has been con- firmed in several studies on rats (Mumby, 2001). The findings are not entirely conclusive, however, because most studies have used retention intervals lasting only a few minutes, and only a small number of them used retention intervals as long as 24–48 h. One of the latter studies reported that HPC lesions impaired performance on a novel-object preference (NOP) test of object recog- nition when the retention interval was 24 h (Clark et al., 2000), suggesting that the HPC makes an impor- tant contribution to object-recognition memory after intervals of more than a few hours. It may also be possi- ble under some conditions to detect object recognition deficits after HPC damage with retention intervals as brief as 1–3 h (Clark et al., 2000; Gould et al., 2002; Broadbent et al., 2004). More recent studies, however, have failed to detect any impairment of NOP in rats with extensive HPC damage after retention intervals last- ing 24 h (Gaskin et al., 2003) or 48 h (Winters et al., 2004; Forwood et al., 2005). Performance has not been assessed after longer delays. Some uncertainty, therefore, remains about the contribution of HPC functions to anterograde object-recognition memory after long reten- tion intervals. The aim of the present experiment was to help resolve the issue by assessing the effects of HPC damage on object recognition after substantially longer delays than those that were used in previous studies. Most procedures used to assess NOP are based on those described by Ennaceur and Delacour (1988). A subject is first habituated to an open-field arena, and later it is placed back in the open field and allowed to investigate two identical sample objects for a few minutes. The subject is then removed for a retention interval, after which it is returned to the arena, which now contains two new objects––one object is identical to the sample and the other is novel. Normal rats spend more time investigating the novel object during Department of Psychology, Center for Studies in Behavioural Neurobi- ology, Concordia University, Quebec, Canada Grant sponsor: Natural Science and Engineering Research Council (NSERC) of Canada; Grant number: 156937-02. *Correspondence to: Dave G. Mumby, Dept. of Psychology, SP-244, Concordia University, 7141 Sherbrooke St. W., Montreal, Quebec, Canada H4B 1R6. E-mail: mumby@vax2.concordia.ca Accepted for publication 1 July 2005 DOI 10.1002/hipo.20122 Published online 6 September 2005 in Wiley InterScience (www.interscience. wiley.com). HIPPOCAMPUS 15:1050–1056 (2005) V V C 2005 WILEY-LISS, INC.