Daniel B&#xE9;racoch&#xE9;a

Georges Chapouthier

Pathological Changes in Memory Processing

Chronic alcohol consumption (CAC) can lead to the Korsakoff syndrome (KS), a memory deficiency attributed to diencephalie damage and/or to medial temporal or cortical related dysfunction. The etiology of KS remains unclear. Most animal models of KS involve thiaminedeficient diets associated with pyrithiamine treatment. Here we present a mouse model of CAC-induced KS. We demonstrate that CAC-generated retrieval memory deficits in working/ episodic memory tasks, together with a reduction of fear reactivity, result from damage to the mammillary bodies (MB). Experimental lesions of MB in non-alcoholic mice produced the same memory and emotional impairments. Drugs having anxiogenic-like properties counteract such impairments produced by CAC or by MB lesions. We suggest (a) that MB are the essential components of a brain network underlying emotional processes, which would be critically important in the retrieval processes involved in working/ episodic memory tasks, and (b) that failure to maintain emotional arousal due to MB damage can be a main factor of CAC-induced memory deficits. Overall, our animal model fits well with general neuropsychological and anatomic impairments observed in KS.

Daniel Béracochéa

Interaction Between Emotion and Memory: Importance of Mammillary Bodies Damage in a Mouse Model of the Alcoholic Korsakoff Syndrome

Most brain insulin comes from the pancreas and is taken up by the brain by what appears to be a receptor-based carrier. Type 2 diabetes animal models associated with insulin resistance show reduced insulin brain uptake and content. Recent data point to changes in the insulin receptor cascade in obesity-related insulin resistance, suggesting that brain insulin receptors also become less sensitive to insulin, which could reduce synaptic plasticity. Insulin transport to the brain is reduced in aging and in some animal models of type 2 diabetes; brain insulin resistance may be present as well. Studies examining the effect of the hyperinsulinic clamp or intranasal insulin on cognitive function have found a small but consistent improvement in memory and changes in brain neuroelectric parameters in evoked brain potentials consistent with improved attention or memory processing. These effects appear to be due to raised brain insulin levels. Peripheral levels of Insulin Growth Factor-I (IGF-I) are associated with glucose regulation and influence glucose disposal. There is some indication that reduced sensitivity to insulin or IGF-I in the brain, as observed in aging, obesity, and diabetes, decreases the clearance of A&#946; amyloid. Such a decrease involves the insulin receptor cascade and can also increase amyloid toxicity. Insulin and IGF-I may modulate brain levels of insulin degrading enzyme, which would also lead to an accumulation of A&#946; amyloid.

Claude  Messier

Kevin  Teutenberg

The Role of Insulin, Insulin Growth Factor, and Insulin-Degrading Enzyme in Brain Aging and Alzheimer&#39;s Disease

Novelty-seeking and harm-avoidance personality traits influence Go/No-go (GNG) learning in humans. Animal studies have also indicated a link between response to novelty and spatial discrimination learning. In the present study, we test the hypothesis that learning rate in a GNG task correlates with the behavioral response of Göttingen minipigs to novelty. In a group of 12 minipigs of mixed genders, response to novelty was measured by numbers of contacts with a novel object, and the total duration of exploration of the novel object. These parameters were correlated to individual learning rate in a GNG task. The number of sessions to reach criterion in the GNG task correlated significantly with the number of contacts to a novel object (r = 0.70, p = 0.03), but not with the duration of object exploration (r = 0.29, p = 0.41). Thus, pigs with a low behavioral response to novelty learned the GNG task faster than did pigs with a strong behavioral response to novelty, indicated by the tendency to approach novel objects. We hypothesize that the critical factor in this relation is difference in emotional reactivity rather than difference in motivation for exploration. In conclusion, in addition to ‘cognitive’ ability, ‘temperamental’ factors are likely to influence learning in individual pigs.

Nanna Marie Lind

Anette Moustgaard

Response to Novelty Correlates with Learning Rate in a Go/No-Go Task in Göttingen Minipigs

Benzodiazepines are well established as inhibitory modulators of memory processing. This effect is especially prominent when applied before the acquisition phase of a memory task. This minireview concentrates on the putative subtype selectivity of the acquisition-impairing action of benzodiazepines. Namely, recent genetic studies and standard behavioral tests employing subtype-selective ligands pointed to the predominant involvement of two subtypes of benzodiazepine binding sites in memory modulation. Explicit memory learning seems to be affected through the <mml:math id="E1" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mtext>GABA</mml:mtext><mml:mtext>A</mml:mtext></mml:msub></mml:math> receptors containing the <mml:math id="E2" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>α</mml:mi><mml:mi>1</mml:mi></mml:msub></mml:math> and <mml:math id="E3" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>α</mml:mi><mml:mi>5</mml:mi></mml:msub></mml:math> subunits, whereas the effects on procedural memory can be mainly mediated by the <mml:math id="E4" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>α</mml:mi><mml:mi>1</mml:mi></mml:msub></mml:math> subunit. The pervading involvement of the <mml:math id="E5" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>α</mml:mi><mml:mi>1</mml:mi></mml:msub></mml:math> subunit in memory modulation is not at all unexpected because this subunit is the major subtype, present in 60% of all <mml:math id="E6" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mtext>GABA</mml:mtext><mml:mtext>A</mml:mtext></mml:msub></mml:math> receptors. On the other hand, the role of <mml:math id="E7" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>α</mml:mi><mml:mi>5</mml:mi></mml:msub></mml:math> subunits, mainly expressed in the hippocampus, in modulating distinct forms of memory gives promise of selective pharmacological coping with certain memory deficit states.

Miroslav M. Savic

Dragan I. Obradovic

Nenad D. Ugrešic

Dubravko R. Bokonjic

Memory Effects of Benzodiazepines: Memory Stages and Types Versus Binding-Site Subtypes

In the current minireview, we focus on genetic mouse models of Alzheimer&#39;s disease (AD). Because various excellent, up-to-date reviews, special issues, and reliable websites are already dedicated to the genetics of Alzheimer&#39;s disease in general and of animal models in particular, this review is not meant to be comprehensive. Rather, we aim to steer the Alzheimer&#39;s novice through the recent mouse literature on AD. Special attention will be paid to genetic models that have been tested behaviorally.

Yann S. Mineur

Declan  McLoughlin

Wim E. Crusio

Frans  Sluyter

Genetic Mouse Models of Alzheimer&#39;s Disease

Systemically administered human recombinant erythropoietin (EPO) may have the potential to reduce the cognitive and behavioral symptoms of mechanical brain injury. In a series of studies, we address this possibility. We previously found that EPO given to fimbriafornix transected rats at the moment of injury could substantially improve the posttraumatic acquisition of an allocentric place learning task when such a task is administered in a water maze. Due to the clinical importance of such results, it is important to scrutinize whether the therapeutic effect of EPO is specific to the experimental setup of our original experiments or generalizes across test situations. Consequently, here we studied the effects of similarly administered EPO in fimbria-fornix transected and control operated rats, respectively, evaluating the posttraumatic behavioral/cognitive abilities in an allocentric place learning task administered in an 8-arm radial maze. The administration of EPO to the hippocampally injured rats was associated with a virtually complete elimination of the otherwise severe behavioral impairment caused by fimbria-fornix transection. In contrast, EPO had no detectable effect on the task acquisition of non-lesioned animals. The results of the present study confirm our previous demonstration of EPO&#39;s ability to reduce or eliminate the behavioral/cognitive consequences of mechanical injury to the hippocampus, while adding the important observation that such a therapeutic effect is not restricted to the specific experimental setup previously studied.

Hana  Mal&#225;

Carina Gili Alsina

Kathrine Skak Madsen

Else la Cour Sibbesen

Henriette  Stick

Jesper  Mogensen

Erythropoietin Improves Place Learning in an 8-Arm Radial Maze in Fimbria-Fornix Transected Rats

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Neural Plasticity is an interdisciplinary journal dedicated to the publication of articles related to all aspects of neural plasticity, with special emphasis on its functional significance as reflected in behavior and in psychopathology.

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Pathological Changes in Memory Processing

Pathological Changes in Memory Processing

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