Klur, S. et al. Hippocampal-dependent spatial memory functions might be lateralized in rats: an approach combining gene expression profiling and reversible inactivation. Hippocampus 19, 800-816

RCMG, F. Hoffmann-La Roche Limited, CH 4070 Basel, Switzerland.
Hippocampus (Impact Factor: 4.3). 09/2009; 19(9):800-16. DOI: 10.1002/hipo.20562
Source: PubMed

ABSTRACT The hippocampus is involved in spatial memory processes, as established in a variety of species such as birds and mammals including humans. In humans, some hippocampal-dependent memory functions may be lateralized, the right hippocampus being predominantly involved in spatial navigation. In rodents, the question of possible lateralization remains open. Therefore, we first microdissected the CA1 subregion of the left and right dorsal hippocampi for analysis of mRNA expression using microarrays in rats having learnt a reference memory task in the Morris water-maze. Relative to untrained controls, 623 genes were differentially expressed in the right hippocampus, against only 74 in the left hippocampus, in the rats that had learnt the hidden platform location. Thus, in the right hippocampus, 299 genes were induced, 324 were repressed, and about half of them participate in signaling and transport, metabolism, and nervous system functions. In addition, most differentially expressed genes associated with spatial learning have been previously related to synaptic plasticity and memory. We then subjected rats to unilateral (left or right) or bilateral reversible functional inactivations in the dorsal hippocampus; lidocaine was infused either before each acquisition session or before retrieval of a reference spatial memory in the Morris water maze. We found that after drug-free acquisition, right or bilateral lidocaine inactivation (vs. left, or bilateral phosphate buffered saline (PBS) infusions) of the dorsal hippocampus just before a delayed (24 h) probe trial impaired performance. Conversely, left or bilateral hippocampus inactivation (vs. right, or bilateral PBS infusions) before each acquisition session weakened performance during a delayed, drug-free probe trial. Our data confirm a functional association between transcriptional activity within the dorsal hippocampus and spatial memory in the rat. Further, they suggest that there could be a leftward bias of hippocampal functions in engram formation or information transfer, and a rightward bias in spatial memory storage/retrieval processes.

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    • "According to previous research (Meyer-Lindenberg et al. 2006) the amygdala, the hippocampus (face-matching task), and the ACC (flanker NoGo task) were defined as ROIs using the anatomical masks implemented in the WFU PickAtlas v2.4 (Maldjian et al. 2003). Separate masks for the left and right amygdala and hippocampus were defined due to lateralized effects of MAOA (Meyer- Lindenberg et al. 2006) as well as evidence for a functional distinction between the 2 hemispheres (Frings et al. 2006; Klur et al. 2009; Schneider et al. 2011; Vrticka et al. 2012). To adjust for multiple comparisons, a P < 0.05 family-wise error (FWE) correction was applied in the ROIs. "
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    ABSTRACT: Converging evidence emphasizes the role of an interaction between monoamine oxidase A (MAOA) genotype, environmental adversity, and sex in the pathophysiology of aggression. The present study aimed to clarify the impact of this interaction on neural activity in aggression-related brain systems. Functional magnetic resonance imaging was performed in 125 healthy adults from a high-risk community sample followed since birth. DNA was genotyped for the MAOA-VNTR (variable number of tandem repeats). Exposure to childhood life stress (CLS) between the ages of 4 and 11 years was assessed using a standardized parent interview, aggression by the Youth/Young Adult Self-Report between the ages of 15 and 25 years, and the VIRA-R (Vragenlijst Instrumentele En Reactieve Agressie) at the age of 15 years. Significant interactions were obtained between MAOA genotype, CLS, and sex relating to amygdala, hippocampus, and anterior cingulate cortex (ACC) response, respectively. Activity in the amygdala and hippocampus during emotional face-matching increased with the level of CLS in male MAOA-L, while decreasing in male MAOA-H, with the reverse pattern present in females. Findings in the opposite direction in the ACC during a flanker NoGo task suggested that increased emotional activity coincided with decreased inhibitory control. Moreover, increasing amygdala activity was associated with higher Y(A)SR aggression in male MAOA-L and female MAOA-H carriers. Likewise, a significant association between amygdala activity and reactive aggression was detected in female MAOA-H carriers. The results point to a moderating role of sex in the MAOA× CLS interaction for intermediate phenotypes of emotional and inhibitory processing, suggesting a possible mechanism in conferring susceptibility to violence-related disorders.
    Cerebral Cortex 10/2014; DOI:10.1093/cercor/bhu249 · 8.67 Impact Factor
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    • "However, when the lesion spares the ventral (temporal) part, learning remains possible (Moser et al., 1993, 1995), suggesting that although the ventral hippocampus contributes to learning, the dorsal hippocampus is required for optimal performance. This has been confirmed using temporal inactivation of the dorsal hippocampus (Hock and Bunsey, 1998; Bannerman et al., 1999; Pothuizen et al., 2004; Klur et al., 2009). The idea that the dorsal hippocampus is involved in spatial navigation is also supported by an electrophysiological study (Jung et al., 1994) as the proportion of cells exhibiting firing related to a specific place is lower in the ventral CA1 than in the dorsal area. "
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    ABSTRACT: In recent years, both major depression and antidepressant therapy have been linked to adult hippocampal neurogenesis. The hippocampus is not a homogeneous brain area, and a converging body of evidence indicates a functional dissociation along its septo-temporal axis, the dorsal part being involved more in learning/memory and spatial navigation, while the ventral sub-region is linked more to emotional behavior and regulation of the neuroendocrine stress axis. Research has therefore been conducted in an attempt to relate effects of models of depression and of antidepressant therapies to adult neurogenesis along the septo-temporal axis of the hippocampus. The present paper reviews the current literature addressing this question and discusses the possible mechanisms involved and the functional significance of such regional effects. This review shows that animal models of depression elicit an effect restricted to the ventral hippocampus more frequently than a dorsal-specific effect. However, this is also stage specific, and concerns neurogenesis, rather than cell proliferation or survival. Surprisingly, the same does not apply regarding the effects of selective serotonin re-uptake inhibitors that act in a more uniform way on dorsal and ventral adult neurogenesis in most studies. Some recently introduced clinical compounds (e.g., agomelatine) or putative antidepressants have a specific action on the ventral sub-region, indicating that an action restricted to this part of the brain may be sufficient to achieve remission. Finally, non-pharmacological manipulations that are also endowed with antidepressant effects, such as environmental enrichment or physical exercise, also act on both subdivisions, although some studies pointed to specificity of dorsal neurogenesis. The different treatments, acting either on the dorsal or on the ventral sub-regions, could promote recovery by improving either ventral- or dorsal-related functions, both contributing in a different way to treatment efficacy.
    Neuroscience 08/2013; 252. DOI:10.1016/j.neuroscience.2013.08.017 · 3.33 Impact Factor
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    • "In this regard, it may seem surprising that pre-acquisition infusions of LIDO into the DHipp failed to induce a dramatic impairment of task acquisition in the current study. This failure, however, is in line with the outcome of our previous study (Klur et al. 2009). The fact that we found no clear impairments of acquisition performance when the DHipp was inactivated could suggest that the hippocampal subregions that were not affected by the drug (i.e., VHipp and intermediate hippocampus) might have been sufficient to support improvement of performance during task acquisition, although they were insufficient to permit optimal performance during the probe trial. "
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    ABSTRACT: Current views posit the dorsal hippocampus (DHipp) as contributing to spatial memory processes. Conversely, the ventral hippocampus (VHipp) modulates stress, emotions and affects. Arguments supporting this segregation include differences in (i) connectivity: the DHipp is connected with the entorhinal cortex which receives visuospatial neocortical inputs; the VHipp is connected with both the amygdala and hypothalamus, (ii) electrophysiological characteristics: there is a larger proportion of place cells in the DHipp than in the VHipp, and an increasing dorsoventral gradient in the size of place fields, suggesting less refined spatial coding in the VHipp, and (iii) consequences of lesions: spatial memory is altered after DHipp lesions, less dramatically, sometimes not, after VHipp lesions. Using reversible inactivation, we report in rats, that lidocaine infusions into the DHipp or VHipp right before a probe trial impair retrieval performance in a water-maze task. This impairment was found at two post-acquisition delays compatible with recent memory (1 and 5 days). Pre-training blockade of the VHipp did not prevent task acquisition and drug-free retrieval, on the contrary to pre-training blockade of DHipp, which altered performance in a subsequent drug-free probe trial. Complementary experiments excluded possible locomotor, sensorimotor, motivational or anxiety-related biases from data interpretation. Our conclusion is that a spatial memory can be acquired with the DHipp, less efficiently with the VHipp, and that the retrieval of such a memory and/or the expression of its representation engages the dorsoventral axis of the hippocampus when the task has been learnt with an entirely functional hippocampus.
    Brain Structure and Function 06/2011; 217(1):93-106. DOI:10.1007/s00429-011-0332-y · 4.57 Impact Factor
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