Exposure to a retrieval cue in rats induces changes in regional brain glucose metabolism in the amygdala and other related brain structures.

Pre-test exposure to training-related cues is known to improve subsequent retention performance. To identify brain regions engaged in processes promoted by retrieval cues, a brain imaging approach using the [6-14C]glucose autoradiographic technique was used. Sprague-Dawley rats trained in a brightness discrimination avoidance task were submitted to different cueing conditions after a 1- or a 21-day training-to-test interval (TTI).

Differential learning-stage dependent patterns of c-Fos protein expression in brain regions during the acquisition and memory consolidation of an operant task in mice.

The present study analysed the effects of the stage of learning of an appetitive operant conditioning task on the spatial and temporal patterns of c-Fos protein levels in the brain of BALB/c mice. c-Fos levels were assessed by immunohistochemistry at either 60, 120 or 180 min after either the first, the second or the fifth daily training session and compared to sham animals. The results show an increase of c-Fos-positive nuclei in several subcortical and cortical brain regions, 60-min post-acquisition.

Time-dependent reorganization of brain circuitry underlying long-term memory storage.

Retrograde amnesia observed following hippocampal lesions in humans and animals is typically temporally graded, with recent memory being impaired while remote memories remain intact, indicating that the hippocampal formation has a time-limited role in memory storage. However, this claim remains controversial because studies involving hippocampal lesions tell us nothing about the contribution of the hippocampus to memory storage if this region was present at the time of memory retrieval. We therefore used non-invasive functional brain imaging using (14C)2-deoxyglucose uptake to examine how the brain circuitry underlying long-term memory storage is reorganized over time in an intact brain.

Sex-linked behavioural differences in mice expressing a human insulin transgene in the medial habenula.

We previously reported that a human insulin transgene was specifically expressed in the medial habenula of the adult mouse brain, and that this expression was ascribed to the delta-168 transgene. The present study analyses the possible behavioural consequences of this insulin transgene expression using measures of food intake, spontaneous activity, emotional reactivity, learning and extinction performance of an operant task. The delta-168 transgenic mice did not differ from the C57BL/6 control mice as concerns food intake, behaviour in the open field, or emotional response in an elevated plus maze.

Blockade of spontaneous posttraining performance improvement in mice by NMDA antagonists.

We investigated the effects of immediate post-training systemic administration of gamma-L-glutamyl-L-aspartate (gamma-LGLA) and 3-(2-carboxypiperazine-4-yl)-propyl-1-phosphonate (CPP), antagonists at the N-methyl-D-aspartate receptor, in a lever-press task in two inbred strains of mice. When retention performance was tested in control animals 24 h after partial acquisition of the task. BALB/c mice exhibited a spontaneous performance improvement whereas C57BL/6J mice did not gamma-LGLA at doses of 2.

Effects of radiofrequency versus neurotoxic cingulate lesions on spatial reversal learning in mice.

Mice with radiofrequency (RF) lesions of the posterior (PC) or anterior (AC) cingulate cortex were trained on spatial discrimination reversal learning in a T-maze. The results were compared with those obtained in an earlier study after ibotenic acid (IBO) cingulate lesions. PC-RF lesions facilitated the initial discrimination and first reversal, whereas they retarded subsequent reversals; in contrast, PC-IBO lesions yielded a deficit on the initial discrimination and first reversal, but had no effect on subsequent reversals.

Differential temporal evolution of post-training changes in regional brain glucose metabolism induced by repeated spatial discrimination training in mice: visualization of the memory consolidation process?

The present study analyses the effects of the stage of learning on the spatial patterns and time-course of [14C]glucose uptake in BALB/c mice brain regions produced by spatial discrimination training in an eight-arm radial maze. Our particular approach was designed to follow, during the post-training period, the level of functional activity in individual brain areas which may underlie the memory consolidation process. Regional mapping of relative [14C]glucose uptake was assessed at three post-training time intervals (5 min, 1 and 3 h) after either the first (Day 1), the fourth (Day 4) or the last (Day 9) daily training session of the discrimination task and compared with sham-conditioned animals placed in the same experimental environment.

Reduction of regional brain glucose metabolism following different durations of chronic ethanol consumption in mice: a selective effect on diencephalic structures.

The effects of chronic alcohol consumption on regional brain glucose metabolism were examined in Balb/c mice using the [14C]2-deoxyglucose autoradiographic technique. Animals were given a solution of 12% v/v ethanol as their only source of fluid for either 6, 12 or 18 months and compared to control groups receiving either an isocaloric solution or saccharose or tap water. Alterations of cerebral brain glucose metabolism were assessed in mice who were returned to a non-alcoholic diet and allowed to freely explore a T-maze.

Differential time courses of c-fos mRNA expression in hippocampal subfields following acquisition and recall testing in mice.

Spatio-temporal patterns of c-fos mRNA expression were studied in the mouse brain following the partial acquisition of an appetitive conditioning task in a Skinner box. We used two experimental situations: during the initial acquisition of the task (acquisition paradigm) and during the retention test (recall paradigm). In both paradigms the in situ hybridization signal was exclusively located in the hippocampal formation and the posterior cingulate cortex.

Post-test apamin injection suppresses a Kamin-like effect following a learning session in mice.

BALB/c mice were trained in a partial acquisition session of an appetitive bar-pressing task. They then received an immediate post-acquisition i.p.

Expression of a human insulin transgene in cholinergic neurons of the mouse medial habenula.

We explored the possibility that an insulin gene deleted in its 5'-flanking region is expressed in adult mouse brain. We used three independent lines of mice carrying a human insulin transgene which included the insulin gene transcription unit flanked by 168 base pairs upstream and 5.5 kb downstream.

Relationships between septo-hippocampal cholinergic activation and the improvement of long-term retention produced by medial septal electrical stimulation in two inbred strains of mice.

This experiment was designed to highlight the relationships between septo-hippocampal cholinergic activation and the processing of memory consolidation. For that purpose, we have analyzed the consequences of a medial septal electrical stimulation (100 Hz, 30 microA) applied soon after partial acquisition session of an appetitive operant conditioning task on in vivo hippocampal cholinergic activity on the one hand and on subsequent retention 24 h later on the other hand. For maximize our data base for such comparison we used two neurochemically and behaviorally distincts strains of mice, BALB/c and C57BL/6.

Memory processing and apamin induce immediate early gene expression in mouse brain.

The present study analyses the effects of learning on the spatial pattern and the time-course of changes of immediate early gene messenger RNA's (c-fos and c-jun) in mouse brain produced by training in an appetitive bar-pressing task. Activation of c-fos and c-jun after training is strictly located in the hippocampal formation and is learning-dependent. Levels of both proto-oncogene mRNAs in the trained group were 4 to 5 times higher than in the sham-conditioned group.

Locomotor bias produced by intra-accumbens injection of dopamine agonists and antagonists.

Several experiments have shown that the dopamine (DA) receptors in the nucleus accumbens control the intensity of locomotor activity; however, there are several contradictory results concerning the role of the accumbens in the regulation of the direction of locomotion. To further evaluate the contribution of dopaminergic function in the accumbens to the direction of locomotion, we first compared the effect on the direction of locomotor activity of unilateral intra-accumbens injections of the nonspecific DA antagonist haloperidol, the specific D-1 antagonist SCH-23390, the specific D-2 antagonist metoclopramide. In the second part of the experiment, we examined the effect on the direction of locomotor activity of unilateral intra-accumbens injections of the non-specific DA agonist apomorphine, the specific D-1 agonist SKF-38393, the specific D-2 agonist LY-171555, and the combination of SKF-38393 and LY-171555.

Differential involvement of anterior and posterior cingulate cortices in spatial discriminative learning in a T-maze in mice.

The contribution of the anterior and posterior cingulate cortical areas to spatial learning and memory was examined in mice using a behavioral paradigm based on a spatial discrimination task in a T-maze. Multiple injections of small amounts of ibotenic acid were used to produce fiber-sparing lesions of either the anterior (ACC) or the posterior (PCC) cingulate area. Mice with ACC lesions, though learning the initial acquisition and first reversal of the discrimination at about the normal rate, were impaired during the subsequent four reversal sessions.

Time-dependent sequential increases in [14C]2-deoxyglucose uptake in subcortical and cortical structures during memory consolidation of an operant training in mice.

Previous results have suggested that memory processing may involve the sequential activation of subcortical and cortical structures. To study this phenomenon, we have examined the immediate (15 min) and delayed (220 min) metabolic changes produced in BALB/c mice by a partial training session in a bar-pressing appetitive task, using the [14C]-2-deoxyglucose (2-DG) relative glucose uptake method. These relative metabolic changes were compared to the ones produced in several control groups: untrained animals, sham-conditioned animals, overtrained animals, and animals forced to walk on a moving belt (immediate and delayed condition).

Effect of apamin, a toxin that inhibits Ca(2+)-dependent K+ channels, on learning and memory processes.

Apamin, a neurotoxin extracted from bee venom, specifically binds to a particular class of Ca(2+)-activated K+ channels which are involved in the slow afterhyperpolarization (S-AHP) that follows action potentials in many excitable cells. We tested in mice the effects of apamin on learning and memory processes. The results showed that pre-training injection of apamin accelerated the acquisition of a bar-pressing response but also increased the bar-pressing rates of the animals.

[Analysis of kinetics of consecutive metabolic cerebral activations induced by spatial discrimination testing, using (14C)-glucose, in an eight-arm radial maze in mice].

Regional mapping of relative (14C)-glucose (GLU) uptake was analyzed in Balb/c mice at 3 time intervals (5 min., 1 hr., 3 hrs.

Locomotor bias produced by intra-accumbens and intracaudate injection of polyclonal dopamine anti-idiotypic antibodies.

The preceding article described anti-idiotypic antibodies to conjugated dopamine (AIDA); results were consistent with the hypothesis that these antibodies contained the internal image of conjugated dopamine (DA-G-BSA) and binded to dopamine (DA) receptors. We further tested these anti-idiotypic antibodies to conjugated dopamine by examining the functional changes produced by unilateral injection of AIDA (or DA-G-BSA) into the nucleus accumbens or into the medio-dorsal caudate in mice. Our results showed that unilateral injection of AIDA (or DA-G-BSA) into the nucleus accumbens or into the medio-dorsal caudate produced an ipsilateral locomotor asymmetry in amphetamine-treated animals which was similar to the one produced by unilateral intra-caudate injection of haloperidol (a non-specific DA antagonist).

Bidirectional potentiation between D1 and D2 dopamine agonists: effects of unilateral intra-accumbens injections on locomotor activity in mice.

We tested the effect of a single unilateral injection of a specific D1 agonist into the nucleus accumbens on the behavioral response to a subsequent unilateral intra-accumbens injection of a selective D2 agonist ten days later. The effect of the inverse order of presentation (D2 agonist followed ten days later by a D1 agonist) was also tested. No significant differences between the locomotor effects of the intra-accumbens injection of either SKF-38393 (3.

Memory-improving action of glucose: indirect evidence for a facilitation of hippocampal acetylcholine synthesis.

The effect of a 3 g/kg glucose injection on the velocity of the sodium-dependent high-affinity choline uptake mechanism in the hippocampus was both measured in quiet control mice and in mice immediately after training in an operant bar pressing task. Glucose did not significantly change high-affinity choline uptake in resting animals. High-affinity choline uptake in the hippocampus was increased by training in the operant bar pressing task.