The spatial working memory performances of young (2 months) and aged (24-26 months) mice of the C57BL/6 strain were compared using a delayed nonmatching to place (DNMTP) protocol in an automated 8-arm radial maze. The aged mice were observed to exhibit a selective and interference-related memory deficit. Parallel neurochemical analysis of the activity of septo-hippocampal and nbm-cortical cholinergic neurones in vivo was conducted using measures of sodium-dependent high-affinity choline uptake. Results showed that whereas the level of cholinergic activity in both brain regions varied less than 10% between young and aged mice in quiet conditions (basal) the activation usually observed at 30-sec posttest (+20-25%) in young mice was greatly attenuated in the frontal cortex and almost totally absent in the hippocampus of aged mice. In view of these results a complementary experiment was carried out in order to test the intrinsic ability of septo-hippocampal cholinergic neurones to activate using acute injection of scopolamine (1 mg/kg IP 20 min) to both young and aged mice in quiet conditions. The drug injection resulted in a very large (+70%) increase in hippocampal high-affinity choline uptake and with amplitudes which did not vary significantly between young and aged subjects. These observations attest to a relatively well-preserved state of central cholinergic neurones and an intact capacity to activate normally when challenged pharmacologically in aged mice. The results strongly suggest that the loss of cholinergic activation and associated memory deficit in aged mice might rather be related to a hypofunction of phasically active transsynaptic processes which normally mediate the activation of these cholinergic pathways during memory testing.

Age Factors↗

PubMedDate not supplied

[Memory consolidation and the hippocampal system].

Explore the source record for details and available documents.

Amnesia, Retrograde↗

PubMedDate not supplied

Further evidence for a dissociation between different forms of mnemonic expressions in a mouse model of age-related cognitive decline: effects of tacrine and S 17092, a novel prolyl endopeptidase inhibitor.

It has been demonstrated previously on the radial maze that the emergence of an age-related mnemonic impairment is critically dependent on the form which the discrimination problems took. Hence, when the arms were presented one by one (i.e., successive go-no-go discrimination), both adult and aged mice learned to distinguish between positive (baited) and negative (unbaited) arms readily, as evidenced by their increased readiness to enter positive relative to negative arms (i.e., by a differential in arm-entry latencies). A selective impairment in the aged mice was seen when these arms were presented subsequently as pairs, such that the mice were confronted with an explicit choice (i.e., simultaneous 2-choice discrimination). When discriminative performance was measured by the differential run speed between positive and negative arms, aged mice were also impaired. This was particularly pronounced in the 2-choice discrimination condition. We examined the effects of tacrine (3mg/kg, subcutaneously) or S 17092 (10mg/kg, orally) in aged mice on the three behavioral indices of this 2-stage spatial discrimination paradigm. The results indicated that: (1) Tacrine, but not S 17092, enhanced the acquisition of go-no-go discrimination as reflected in arm-entry latencies; (2) both drugs improved choice accuracy in simultaneous discrimination, although the effect of tacrine was less striking and, in particular, far from statistical significance in the very first 2-choice responses; and (3) neither drugs significantly affected run-speed performance. We conclude further that the specific patterns of drug effects on the three indices of discriminative performance might suggest that each index is associated with a distinct form of mnemonic expression relying on separate neural systems.

Aging↗

PubMedDate not supplied

[An animal model of human declarative (relational) memory and of its dysfunction].

The present work was aimed at determining, both at the psychological and at the neurobiological levels, aspects of rodent memory that fall into line with human declarative memory which is known to be selectively impaired in amnesic subjects and during the course of ageing. The ability to compare and to contrast items in memory, and to support inferential use of memories in novel situations (flexibility), were considered to be the two key psychological features of human declarative memory that were altered by both hippocampal lesions and hippocampal dysfunction. Adult and aged mice were trained on learning tasks using two-stage paradigms, the aim of which was to assess memory performance through these two psychological aspects in the same subjects. Results suggest that ageing specifically impairs the ability to both compare and contrast items in memory (declarative/relational memory based on complex associations), without altering memory based on simple S-R associations (procedural memory). Hippocampal lesions in adult mice produced the same dissociation between relational memory (impaired) and procedural memory (spared). Pharmacological experiments showed that, depending on the drug used, the relational memory deficit of aged mice may be selectively reversed (i.e. without changes in procedural memory) and that the behavioural efficacy of certain treatments was shown to parallel their potency in re-establishing normal (i.e. adult) levels of hippocampal plasticity-related mechanisms. Together with previous findings, these results suggest that the storage and use of relational representations would critically depend on the plasticity of hippocampal synapses, which via their connections with cortical areas, would support the storage of associations between perceptual, behavioral and cognitive events.

Animals↗

PubMedDate not supplied

[Comparison of the effects of tianeptine and paroxetine on amnesic deficits induced by prolonged alcohol drinking in mice].

Previous experiments have shown that chronic ethanol consumption in mice for 12 months produced memory deficits associated with both alterations in diencephalic structures (ie, cellular loss, hypometabolism, particularly in mamillary bodies) and with hippocampal and cortical cholinergic hypofunction (Béracochéa et al., Pharmacol Biochem Behav 1992; 42: 749-53). The present study was aimed at comparing the effects of tianeptine and paroxetine (10 mg.kg-1, i.p.), that have opposite properties on serotoninergic transmission, on this alcohol-induced memory deficits. For this purpose, animals were submitted to a T-maze sequential alternation task in which they were given daily series of 6 successive trials separated by a 30-second interval. Behavioural testing began following a 4-week complete withdrawal period. The experiment was conducted in two steps. In the first part, animals received no treatment. Results showed that, as compared to the control group (pair-fed, n = 7), alcohol-treated mice (n = 20) displayed a trial-specific impairment of alternation rates. Specifically, they were impaired on the last three trials (4-6) of the series (52.2 vs 81.0%, p < 0.001), but performed normally on the first ones (2-3), suggesting thereby an increased sensitivity to proactive interference (Béracochéa et al., Behav Brain Res 1987; 25: 63-74). In the second part of the experiment the alcohol group was divided into three homogeneous groups according to the treatment they received 30 minutes before each daily session (ie, placebo, tianeptine, paroxetine).(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Amnestic Disorder↗