Research reportAssessing rodent hippocampal involvement in the novel object recognition task. A review
Introduction
We can all recall a time when walking down a crowded corridor, we happen upon a person who looks familiar. While we are confident that we have encountered this person before, we are unable to remember how or when we previously met. It is only through the information gathered during interactive conversation that we are able to recall who this person is and where we encountered them for the first time. This uncomfortable, yet common, scenario depicts our ability to subjectively recall previous information through distinct memory processes.
Memory can be divided into two distinct categories, declarative and non-declarative forms. Declarative memory, or explicit memory, is the ability to recall personal history, facts and events, and is dependent on the interconnected structures of the medial temporal lobe. Recognition, a subtype of declarative memory, reflects that of people, objects, and experiences. Clearly, the example stated above illustrates the two forms of recognition memory that are commonly experienced during a test of information retrieval, that is, familiarity and recollection. Familiarity is the immediate feeling that an event, individual, or item was previously encountered. This experience, referred to as ‘knowing’, does not involve the conscious recollection of details from the prior experience. For example, “I know I have seen that person (or item) before; I just don’t remember where or when”. Recollection, or ‘remembering’ on the other hand, involves a slower process whereby full attention to the present stimuli (if any) induces an intended or conscious recall of the contextual details of the prior event or experience – that is, specific information as to where and when the original experience occurred [1], [2]. For example, “I remember you. We met at the 2012 Society for Neuroscience meeting; our posters were next to one another on the second day of that conference, and you commented on how well I coordinated my outfit with the color scheme of my poster”. Originally defined by Tulving [3], the remember/know distinction is considered by many to reflect separate underlying behavioral processes of recognition memory. Although the processes of recollection and familiarity are distinct in the manner that they are experienced, it remains unclear whether different neurobiological mechanisms support them. Dual-process models of recognition memory state that recollection and familiarity are functionally separate systems [4], [5], [6], [7], [8]. Studies of human amnesiacs have revealed selective impairment of recollection, while sparing familiarity, and numerous functional imaging studies have identified that the separate processes are associated with region-specific activation patterns. These findings are largely considered support for the view that familiarity and recollection utilize different underlying systems [9], [10], [11]. On the other hand, single-process models view the two declarative memory forms as a part of one distinct category of recognition memory [7], [10], [12]. Here, memories are represented along a scale that ranges from weak to strong. Studies have demonstrated that these two processes have a significant structural commonality that would point to a single process model. Similar structural activation is observed with both familiarity and recollection [11]. Regardless of how these forms of memory are thought to function, the fundamental concepts derived from the distinction between familiarity and recollection are useful for improving understanding of recognition memory mechanisms in both humans and laboratory animals.
The medial temporal lobe is organized in a manner that supports memory. Various sub-regions have been identified as the structures critical in supporting memory in a variety of species [13]. The perirhinal cortex, parahippocampal cortex, and entorhinal cortex are anatomical structures identified as components of the “what” and “where” streams of experience-dependent sensory inputs that converge within the hippocampus. Traditionally, it is believed that the “what” information is conveyed through the perirhinal cortex, while the “where” information is transmitted through the parahippocampal and entorhinal cortices. It is only in the hippocampus that the “what” and “where” information is associated [1]. However, in recent years, debate over whether the hippocampus is directly involved in encoding memories of the “what” information has increased. Similarly, many studies claim that familiarity is structurally distinct from that of recollection, with familiarity attributed to the perirhinal cortex and recollection to the hippocampus [14]. Nevertheless, it is apparent that during recollection, it is the “what” and “where” associations that are being recovered.
In general, memories are formed and stabilized through three distinct processes. Encoding refers to the initial acquisition of the memory. Then, through phases of consolidation, the memory is preserved and stored for later recall. Finally, retrieval is the process by which the previously stored memories are reactivated. Many different tasks have been developed to investigate the neural basis of memory and its distinct stages. However, it is important to note that all methodologies have limitations, which should be considered when analyzing outcomes. Human recognition memory is commonly tested in the visual paired comparisons task [15], [16], while a modified version of the task has been implemented for rodents [17]. Functional imaging studies, in humans, have identified patterns of region-specific neural activation associated with recollection and familiarity; however, animal models enable investigation of the neurobiological circuitry and cellular mechanisms of recognition memory, which are not possible in humans.
Section snippets
Task procedures and behavior quantification
Implicit to the animal model approach is the necessity that the behavioral constructs that are modeled in rodents match to a large extent, human recognition memory. To this end, the spontaneous novel object recognition (NOR) task has emerged as the most popular test for assessing a rodent's ability to recognize a previously presented stimulus [18]. Describing the task as such is misleading since it is not theoretically possible to recognize a novel object since recognition reflects prior
Effects by size of permanent lesion
The NOR task has been applied extensively to decipher the differential contributions of rodent medial temporal lobe structures to object recognition memory. Permanent lesions have been traditionally used to investigate the role of a brain structure in a given behavior, or to establish brain region–behavioral relationships. The functions impaired, or the differences in behavior observed between sham and lesioned rodents, are then interpreted as those dependent upon the damaged or absent region.
Conclusions
In summary, the goal of our review was to evaluate the current literature regarding the role of the rodent hippocampus in object recognition memory as assessed with the NOR task. As discussed, this literature is divisive and replete with conflicting results. Our analysis of those 12 published reports that met our exclusion criteria and in which temporary or permanent lesions were employed, revealed remarkable differences in experimental outcomes depending on the method of hippocampal lesion
Acknowledgment
This work was supported in part by NIMH MH086591 to RWS.
References (79)
- et al.
Human recognition memory: a cognitive neuroscience perspective
Trends Cogn Sci
(2003) The nature of recollection and familiarity: A review of 30 years of research
J Mem Lang
(2002)- et al.
The eyes have it: hippocampal activity predicts expression of memory in eye movements
Neuron
(2009) - et al.
Dissociable correlates of recollection and familiarity within the medial temporal lobes
Neuropsychologia
(2004) Memory in the infant
J Exp Child Psychol
(1970)- et al.
Measuring infant memory: utility of the visual paired-comparison test paradigm for studies in developmental neurotoxicology
Neurotoxicol Teratol
(2012) One-trial object recognition in rats and mice: methodological and theoretical issues
Behav Brain Res
(2010)- et al.
A new one-trial test for neurobiological studies of memory in rats. 1: Behavioral data
Behav Brain Res
(1988) - et al.
Object recognition memory: neurobiological mechanisms of encoding, consolidation and retrieval
Neurosci Biobehav Rev
(2008) - et al.
Distinct patterns of behavioural impairments resulting from fornix transection or neurotoxic lesions of the perirhinal and postrhinal cortices in the rat
Behav Brain Res
(2000)
The rodent hippocampus is essential for nonspatial object memory
Curr Biol
On the delay-dependent involvement of the hippocampus in object recognition memory
Neurobiol Learn Mem
Chronic stress effects on memory: sex differences in performance and monoaminergic activity
Horm Behav
The rodent hippocampus is essential for nonspatial object memory
Curr Biol
On the delay-dependent- involvement of the hippocampus in object recognition memory
Neurobiol Learn Mem
Changes in immediate early gene expression in the rat brain after unilateral lesions of the hippocampus
Neuroscience
Experience-dependent structural plasticity in the adult human brain
Trends Cogn Sci
Teaching an adult brain new tricks: a critical review of evidence for training-dependent structural plasticity in humans
NeuroImage
Imaging the spread of reversible brain inactivations using fluorescent muscimol
J Neurosci Methods
Intraseptal administration of muscimol produces dose-dependent memory impairments in the rat
Behav Neural Biol
A method to measure the effective spread of focally injected muscimol into the central nervous system with electrophysiology and light microscopy
J Neurosci Methods
Autoradiographic estimation of the extent of reversible inactivation produced by microinjection of lidocaine and muscimol in the rat
Neurosci Lett
Temporary inactivation reveals an essential role of the dorsal hippocampus in consolidation of object recognition memory
Neurosci Lett
The pharmacology, neuroanatomy and neurogenetics of one-trial object recognition in rodents
Neurosci Biobehav Rev
Recognition memory: an old idea given new life
Curr Biol
The medial temporal lobe and the attributes of memory
Trends Cogn Sci
Of mice and mazes: similarities between mice and rats on dry land but not water mazes
Physiol Behav
The role of the hippocampus in object recognition in rats: examination of the influence of task parameters and lesion size
Behav Brain Res
The effects of neurotoxic lesions of the perirhinal cortex combined to fornix transection on object recognition memory in the rat
Behav Brain Res
The medial temporal lobe and recognition memory
Annu Rev Neurosci
Dissociating familiarity from recollection in human recognition memory: different rates of forgetting over short retention intervals
Psychon Bull Rev
Memory and consciousness
Can Psychol
Combined pharmacological and electrophysiological dissociation of familiarity and recollection
J Neurosci
Modeling hippocampal and neocortical contributions to recognition memory: a complementary-learning-systems approach
Psychol Rev
Separating the brain regions involved in recollection and familiarity in recognition memory
J Neurosci
Episodic memory, amnesia, and the hippocampal-anterior thalamic axis
Behav Brain Sci
Recognition memory and the medial temporal lobe: a new perspective
Nat Rev Neurosci
Dual-process theory and signal-detection theory of recognition memory
Psych Rev
The parahippocampal region: corticocortical connectivity
Ann N Y Acad Sci
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Author contributions: S.J.C. and R.W.S. wrote the paper.