Elsevier

Behavioural Brain Research

Volume 256, 1 November 2013, Pages 140-150
Behavioural Brain Research

Research report
Determinants of novel object and location recognition during development

https://doi.org/10.1016/j.bbr.2013.07.055Get rights and content

Highlights

  • Object and spatial novelty recognition is evident around the time of weaning.

  • Spatial recognition requires NMDA receptor function in juvenile rats.

  • Neonatal alcohol exposure does not impair novel object or spatial recognition.

Abstract

In the novel object recognition (OR) paradigm, rats are placed in an arena where they encounter two sample objects during a familiarization phase. A few minutes later, they are returned to the same arena and are presented with a familiar object and a novel object. The object location recognition (OL) variant involves the same familiarization procedure but during testing one of the familiar objects is placed in a novel location. Normal adult rats are able to perform both the OR and OL tasks, as indicated by enhanced exploration of the novel vs. the familiar test item. Rats with hippocampal lesions perform the OR but not OL task indicating a role of spatial memory in OL [1]. Recently, these tasks have been used to study the ontogeny of spatial memory but the literature has yielded conflicting results [2], [3]. The current experiments add to this literature by: (1) behaviorally characterizing these paradigms in postnatal day (PD) 21, 26 and 31-day-old rats; (2) examining the role of NMDA systems in OR vs. OL; and (3) investigating the effects of neonatal alcohol exposure on both tasks. Results indicate that normal-developing rats are able to perform OR and OL by PD21, with greater novelty exploration in the OR task at each age. Second, memory acquisition in the OR but not OL task requires NMDA receptor function in juvenile rats. Lastly, neonatal alcohol exposure does not disrupt performance in either task. Implications for the ontogeny of incidental spatial learning and its disruption by developmental alcohol exposure are discussed.

Introduction

Previous research concerning the developmental emergence of hippocampus-dependent learning and memory has largely focused on reinforcement-driven tasks, such as Pavlovian fear conditioning and appetitive maze learning [4], [5], [6]. Typically, performance of the hippocampus-dependent variant emerges later in ontogeny than control tasks that do not require the hippocampus. For example, auditory fear conditioning emerges by postnatal day (PD)16–18, followed by contextual fear conditioning, which emerges around PD23 [4], [7], [8], [9] and T-maze delayed alternation develops later than position discrimination [5], [10]. These findings have been attributed to a delay in hippocampal development and function, which causes spatial learning to develop later than non-spatial forms of learning.

Incidental learning encompasses an animal's natural exploratory tendency when presented with novel environmental stimuli [11], [12]. There are spatial and nonspatial variants of incidental learning. The standard object recognition task (OR) includes exposure to two identical objects (sample phase). Following a delay, the animal is presented with a familiar, as well as a novel object (testing phase). The spatial variant, the object location task (OL), is identical to the object version; however, the testing phase includes a familiar object situated in a novel spatial location [1], [13], [14], [15], [16], [17], [18]. In both cases, preference for the novel object or the object in a novel location is a result of incidental learning occurring during the sample phase and exploratory behavior during the testing phase. One-trial object recognition paradigms provide an opportunity to examine incidental conjunctive processing functions of the hippocampus without the need for repeated conditioning trials or reinforcement contingencies. Incidental learning is thought to be more sensitive than reinforcement-driven learning to disruptions of hippocampal function [12].

Different brain regions contribute to performance of the OR and OL tasks, at least during adulthood. Perirhinal cortex (PER) is required for OR task performance, while the hippocampus (HPC) is required for OL performance [1], [15], [16], [17], [18]. Studies of the OR task and hippocampal NMDA-receptor (NMDAr) function have produced mixed results, depending on the delay interval between the sample and testing phases [19]. For example, NMDAr antagonists administered either systemically or intrahippocampally prior to acquisition of the OR task disrupts performance with delays ranging from 1 to 24 h [20], [21], [22], [23]. However, OR performance remains intact following intra-hippocampal infusions with a 5-min delay between the sample and testing phases [22]. Similarly, intra-perirhinal cortex infusion of AP5 prior to the sample phase impairs OR after a 3 h but not a 5-min delay [24]. Studies in adult rats implicate the role of NMDArs in the OL task [25], [26]; however, the effect of NMDAr antagonists in the OR and OL task has, to our knowledge, not been examined during development.

The sensitivity of incidental conjunctive learning to hippocampal injury [12] makes it of great value to study developmental neurobehavioral disorders that involve the hippocampus [27], [28]. For example, developmental alcohol exposure produces teratogenic effects in various brain regions, such as the cerebellum and hippocampus [29], [30] and impairs neurobehavioral function, including spatial memory in humans [31], [32]. Fetal alcohol spectrum disorders (FASDs) affect approximately 2–5 in 100 young children in the U.S. and abroad [33]. In rat models of FASDs, in which alcohol exposure is limited to PD4–9, the third trimester equivalent of human pregnancy, converging neuroanatomical and behavioral evidence reveals hippocampal CA1 [34], [35], [36] and CA3 pyramidal cell loss [34]. Ethanol administration restricted to PD7–9 also impairs performance in hippocampus-dependent maze and fear conditioning tasks [37], [38], [39], possibly through inhibited induction and transmission of long-term potentiation (LTP) and reduction of hippocampal NMDArs [40], [41], [42].

The current report extends previous work from our lab addressing spatial learning and NMDAr function during development and the effect of neonatal alcohol exposure on this function [27], [28], [43], [44], [45]. The OR and OL tasks are being developed here as a probe for examining these issues with incidental learning paradigms. Previous research concerning the developmental emergence of various object recognition paradigms has provided mixed results [2], [3] and the developmental role of NMDArs in the non-spatial OR and spatial OL tasks has not been examined. Recent findings from our lab demonstrate that PD7-9 ethanol administration impairs performance of a contextual fear conditioning task that involves incidental learning [27]. Thus, the OR and/or the OL tasks may provide converging evidence for incidental learning deficits as a function of developmental alcohol exposure.

In summary, the purpose of this study was to examine the effects of age, NMDAr antagonists, and neonatal alcohol on OR and OL in juvenile rats. Experiment 1 evaluated the ability of normally-developing weanling and juvenile rats to perform both tasks. The amount of habituation to the empty chamber was manipulated in order to determine how much exposure to the spatial environment was optimal for task performance. Experiment 2 determined whether or not antagonism of NMDArs would impair performance in either or both of these tasks. Based on prior studies with systemically administered MK-801 in spatial learning tasks, we predicted administration prior to acquisition would impair the OL, but not the OR task. Finally, Experiment 3 examined the effects of neonatal alcohol exposure with a dose and window of administration found to be effective in disrupting hippocampal-dependent forms of learning.

Section snippets

Experiment 1A: behavioral determinants of developmental object and spatial location memory

Previous research concerning variations of the OR and OL object recognition paradigms during development has produced mixed results [2], [3], [46], [47], [48], highlighting the need for a more systematic approach for examining these tasks. Thus, Experiment 1A sought to compare the OR and OL tasks as a function of empty chamber habituation and sex by using an age during the late stage of postnatal development when performance in these tasks would be expected.

Experiment 1B: ontogeny of object and spatial location memory

The ability of animals to express learning of spatial tasks develops around PD21 in the rat, whereas performance of non-spatial control tasks develops earlier (e.g., [4], [5], [6], [49]). Experiment 1B extends the findings of Experiment 1A by examining object vs. spatial novelty in PD21 and 26 rats. This experiment seeks converging evidence on previous developmental studies of spatial learning that examined spatial learning that is “incidental” rather than “reinforcement-driven” [11], [45], [49]

Experiment 2: the effect of NMDA receptor antagonism on object vs. spatial novelty

NMDA receptor function in areas such as the hippocampus and prefrontal cortex has been implicated in the postnatal development of various forms of contextual and spatial memory (e.g., [45], [51]. In Experiment 2, PD31 rats received systemic administration of an NMDA receptor antagonist or vehicle prior to acquisition in the novel object and spatial recognition tasks in order to determine whether learning and performance of these tasks (especially spatial novelty) is NMDA-dependent in juveniles,

Experiment 3: the effect of neonatal alcohol exposure on object and spatial location memory

Neonatal alcohol exposure has been found to disrupt a variety of spatial learning tasks, including context representations incidentally acquired during the context preexposure facilitation effect (CPFE) [27], [28]. Using an identical alcohol dose and window of exposure (PD7-9), Experiment 3 asked if these findings would extend to another incidental form of spatial learning, novel location recognition.

General discussion

Four experiments behaviorally characterized the non-spatial OR (novel object recognition) task and the spatial OL (object location) task during development in the rat. Experiment 1A demonstrated the ability of normal-developing juvenile rats to perform both the OR and OL tasks. Experiment 1B extended these findings to pups as young as PD21. Experiment 2 determined that performance of the OL but not OR task requires NMDA receptor function. Lastly, Experiment 3 found that neonatal alcohol

Conflict of interest

The authors have no conflict of interest to declare.

Acknowledgements

The authors would like to thank Lisa B. Dokovna for assistance with behavioral data collection and the University of Delaware Office of Laboratory Animal Medicine (OLAM) for the care of the animals. The study was supported by 1-R21-HD070662-01.

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