Research reportc-Fos expression correlates with performance on novel object and novel place recognition tests
Introduction
When rats are exposed to a previously-encountered object and a novel object, they frequently approach and spend more time exploring the novel object than the familiar one. This preference for a novel object indicates that rats maintain a representation of the familiar object in memory (Ennaceur, 2010). This spontaneous behaviour is the basis for one-trial object recognition tests (Dere et al., 2005, Ennaceur and Delacour, 1988, Ennaceur et al., 2005, Ennaceur et al., 2009), which have been widely used to study recognition memory in mice and rats. Tests assessing this type of memory, which consists of the ability to judge a previously encountered item as familiar, have often been used in basic research to investigate the neural basis of recognition memory (Winters et al., 2008). The most well-known recognition test is the one-trial object recognition test, which assesses the ability of rats to identify a particular object as novel or familiar based on the memory of an earlier experience with one of the two objects encountered in the same open-field (memory of “what”). However, this novelty preference paradigm has also been used to assess memory of the location of an object. This test assesses to what extent animals recognize the non-displaced object and, thus, spend more time exploring the displaced one (memory for “where”).
There is a large body of evidence about the role of the perirhinal cortex and the hippocampus in these two tasks. Many studies using a variety of methods and techniques have indicated that the perirhinal cortex is fundamental in novel object recognition (“what”). Lesion and electrophysiological studies suggest that the perirhinal cortex is critical for encoding object information, maintaining the object memory trace during the consolidation period and retrieving object information during the test trial (Brown and Aggleton, 2001, Winters and Bussey, 2005, Winters et al., 2008). At the same time, the hippocampus plays a fundamental role in place memory (“where”). Damage to the hippocampal system affects tasks involving the recognition of stimuli rearranged within a scene (Gaffan and Parkerm, 1996). Other studies, using measures of neuronal activation, also reveal an important role of the hippocampus in remembering what particular objects are located in specific locations (Manns and Eichenbaum, 2009, Castilla-Ortega et al., 2012).
Functional evidence about the role of the perirhinal cortex and hippocampus in the recognition of objects and places, respectively, has also been provided by imaging experiments using the products of the immediate early gene c-fos as an index of neuronal activation in response to stimulus exposure. The c-fos-encoded protein, c-Fos, is the product of the c-fos oncogene, an immediate-early gene. c-Fos can provide information about the neuronal plasticity required for memory processes and object recognition tests. Specifically, c-Fos studies showed increasing activity in rats’ perirhinal cortex following exposure to novel objects, whereas novel spatial arrangements of familiar objects significantly activated area CA1 of the hippocampus (Aggleton and Brown, 2005, Wan et al., 1999, Zhu et al., 1995, Zhu et al., 1996).
Therefore, perirhinal cortex involvement has been clearly shown in the representation of individual object information useful for recognition processes, whereas the hippocampus plays a specific role in more spatial functions (for review, see Winters et al., 2008). However, these studies do not explore whether levels of c-Fos in these brain areas correlate with performance on the respective versions of the novelty preference tests. For this purpose, in this study we employed novelty-preference tests similar to those developed by Ennaceur and Delacour (1988) and Mitchell and Laiacona (1998), which distinguish “what” and “where” information in order to assess whether c-Fos expression in these specific brain areas depends on the magnitude of novel object or novel place exploration.
Section snippets
Animals
We used 24 male Wistar rats from the vivarium of the University of Oviedo that weighed 290–330 gm at the beginning of the study. Rats were housed in groups of 4 three weeks prior to the beginning of the experiments and maintained under standard laboratory conditions (20–22 °C, 65–70% relative humidity and a 12 h light/dark cycle). Food and water were available ad libitum throughout all the experiments, and sessions were performed during the light phase, between 9:00 a.m. and 13:00 p.m. All
What
The results showed that rats were able to discriminate between a previously-encountered object and a novel object, as the means for d1 and d2 were both significantly higher than zero (d1: t7 = 4.663, p = 0.002; d2: t7 = 5.407, p = 0.001) (Fig. 3B). There were no significant differences in exploration between the sample and test phases (e1 = 0.496 ± 0.021, e2 = 0.485 ± 0.032: t7 = 0.276, p = 0.791) (Fig. 3A).
Where
The results showed that rats were able to discriminate between a location within the open field that had
Discussion
We assess whether the expression of the immediate-early gene c-fos in the dorsal hippocampus and perirhinal cortex correlates with the performance discrimination ratio (d2) on the “what” and “where” variants of a novelty-preference paradigm. This study related c-fos activity and the level of effective recognition in rats performing the test trial of novelty-preference tests of object and place discrimination. The results of this study reveal that CA1 is specifically involved in the recognition
Conflict of interest
All authors declare that there are no actual or potential conflicts of interest including any financial, personal or other relationships with other people or organizations that could inappropriately influence this work.
Acknowledgements
This research was supported by Project Grants of the Spanish Ministry of Economy and Competitiveness: PSI 2010-19348 and PSI 2013-45924; MEC Grant AP2009-1714 and Alfonso Martín Escudero Foundation to NA and USE-07750-E to SU.
References (46)
- et al.
Contrasting brain activity patterns for item recognition memory and associative recognition memory: insights from immediate-early gene functional imaging
Neuropsychologia
(2012) - et al.
Object recognition testing: methodological considerations on exploration and discrimination measures
Behav. Brain Res.
(2012) - et al.
Expression of c-fos, ICER, Krox-24 and JunB in the whisker-to-barrel pathway of rats: time course of induction upon whisker stimulation by tactile exploration of an enriched environment
J. Chem. Neuroanat.
(2002) - et al.
Hippocampal c-fos activation in normal and LPA₁-null mice after two object recognition tasks with different memory demands
Behav. Brain Res.
(2012) - et al.
Integrated memory for objects, places, and temporal order: evidence for episodic-like memory in mice
Neurobiol. Learn. Mem.
(2005) - et al.
Extending the spontaneous preference test of recognition, evidence of object–location and object–context recognition
Behav. Brain Res.
(1999) One-trial object recognition in rats and mice: methodological and theoretical issues
Behav. Brain Res.
(2010)- et al.
The effects of neurotoxic lesions of the perirhinal cortex combined to fornix transection on object recognition memory in the rat
Behav. Brain Res.
(1997) - et al.
A new one-trial test for neurobiological studies of memory in rats. 1: behavioral data
Behav. Brain Res.
(1988) - et al.
Detailed analysis of the behavior of Lister and Wistar rats in anxiety, object recognition and object location tasks
Behav. Brain Res.
(2005)
Do rats really express neophobia towards novel objects? Experimental evidence from exposure to novelty and to an object recognition task in an open space and an enclosed space
Behav. Brain Res.
Incidental (unreinforced) and reinforced spatial learning in rats with ventral and dorsal lesions of the hippocampus
Behav. Brain Res.
Object familiarization and novel-object preference in rats
Behav. Processes
Prolonged inactivation of the hippocampus reveals temporally graded retrograde amnesia for unreinforced spatial learning in rats
Neurobiol. Learn. Mem.
A computational theory of hippocampal function, and tests of the theory: new developments
Neurosci. Biobehav. Rev
The medial frontal cortex and temporal memory: tests using spontaneous exploratory behaviour in the rat
Behav. Brain Res.
Perirhinal cortex damage and anterograde object-recognition in rats after long retention intervals
Behav. Brain Res.
Perspectives on object-recognition memory following hippocampal damage: lessons from studies in rats
Behav. Brain Res.
Cholinergic neurotransmission is essential for perirhinal cortical plasticity and recognition memory
Neuron
Object recognition memory: neurobiological mechanisms of encoding, consolidation and retrieval
Neurosci. Biobehav. Rev.
Differential induction and decay curves of c-fos and zif268 revealed through dual activity maps
Brain Res. Mol. Brain Res.
Effects of the novelty or familiarity of visual stimuli on the expression of the immediate early gene c-fos in rat brain
Neuroscience
Contrasting hippocampal and perirhinal cortex function using immediate early gene imaging
Q. J. Exp. Psychol. B
Cited by (36)
Increased hippocampal CREB phosphorylation after retrieval of remote contextual fear memories in Carioca high-conditioned freezing rats
2023, Neurobiology of Learning and MemoryHippocampal alterations after SARS-CoV-2 infection: A systematic review
2023, Behavioural Brain ResearchCopper nanoclusters based short-term memory “eraser”
2023, Chemical Engineering JournalOntogeny of spontaneous recognition memory in rodents
2021, Neurobiology of Learning and Memory