Biomedical subjects

R Jaffard

Publications and source records attributed to R Jaffard.

At least 55 records · Page 3Linked to original sources

PubMed1995

Spatial location learning in mice with ibotenate lesions of entorhinal cortex or subiculum.

This study examined the effects of ibotenate lesions of either the entorhinal cortex (EC) or the subiculum (SUB) on the ability of mice to memorize a single spatial location (initial discrimination), and on their capacity to switch to a new location (transfer) following the initial learning in an eight-arm radial maze. Results indicated that mice with ibotenate lesions of the EC or SUB were impaired in postoperative acquisition of the spatial discrimination task, making more reference, but not working memory, errors and displaying fewer first correct response trials than sham-operated control mice. Furthermore, additional damage to the ventral hippocampus exacerbated the impairment of performance induced by lesions of the SUB alone. In addition, all mice, except for the combined lesion group, exhibited similar performance levels when they were trained to choose another arm of the maze that had not previously been baited (transfer). These findings suggest that both the EC and the SUB play important roles in spatial information processing in mice.

Animals↗

PubMed1995

Effects of mammillary bodies and mediodorsal thalamic lesions on the acquisition and retention of a learning set in mice: paradoxical effect of the intersession interval.

The effects of ibotenic acid lesions of either the mediodorsal thalamus (MD) or the mammillary bodies (MB) on the acquisition and retention of a reversal learning set in a T-maze were studied in mice. Both the MB and MD lesions disrupted performance in this task, but only MD lesions slowed down the rate of learning, MD-lesioned subjects requiring more trials than the other two groups to master the discrimination at the end of the learning phase. Surprisingly, increasing the intersession interval from 24 h to 10 days totally alleviated the deficit of MD-subjects and even improved their performance as compared to the last (8th day) session. The overall results of the study show that both MD and MB lesions do not induce important learning deficits nor anterograde amnesia in the reversal learning set task.

Animals↗

PubMed1995

The effects of mammillary body lesions on delayed matching and delayed non-matching to place tasks in the mice.

This study was designed to investigate the effects of different recognition procedures on memory performance in Balb/c mice. To this end, mice were submitted to spontaneous or contingently reinforced delayed non-matching (DNMTP) and delayed matching (DMTP) to place tasks in a T-maze. Results indicate that mammillary bodies (MM)-lesioned subjects are significantly impaired in the DNMTP tasks at the long (6 h) but not the short (5 min) delays; in contrast, they did not exhibit deficits in the DMTP task, whatever the delay considered. We stress the importance of task difficulty as a major factor explaining the different effects of the lesion in the two tasks.

Animals↗

PubMed1994

The entorhinal cortex and a delayed non-matching-to-place task in mice: emphasis on preoperative training and presentation procedure.

This study examined the effects of ibotenate lesions of the entorhinal cortex (EC) on performance of a spatial recognition memory task, the delayed non-matching-to-place task (DNMTP), varying in level of difficulty according to the number of interpolated arm visits between sample-place presentation and subsequent recognition in mice. Results of experiment 1, designed to test the rate of acquisition of the task, showed that experimental animals were impaired in the basic non-matching task. However, with further training they were able to learn the task. Impairments were also observed when the amount of interpolating information inserted was gradually increased, and then all problem difficulties were pseudorandomly tested. There was no measurable recovery of function over time when the animals were retested on the task approximately 1 month later. Experiment 2 showed that the animals that received extensive training on the task prior to lesions of the EC were only transiently impaired in the DNMTP task. These data suggest that the EC plays an important role in acquisition rather than retention of the spatial recognition memory task.

Animals↗

PubMed1994

Effects of intraseptally injected noradrenergic drugs on hippocampal sodium-dependent-high-affinity-choline-uptake in 'resting' and 'trained' mice.

It has been shown in numerous studies that memory testing can alter presynaptic cholinergic activity within the hippocampus. In the present experiments, the role of the noradrenergic input to the septal cholinergic neurons in the immediate increase in cholinergic activity induced by the first training session of a spatial reference memory task in an 8-arm radial maze was investigated. The effects of bilateral intraseptal injections of noradrenergic drugs on hippocampal sodium-dependent-high-affinity-choline-uptake (SDHACU) were studied in 'resting' animals (basal level) or in 'trained' animals injected 20 min before training and sacrificed immediately after the test. The results showed that: (1) the injection of maprotiline, a noradrenaline reuptake inhibitor (0.06 ng/site), induced an increase in hippocampal SDHACU in 'resting' animals, whereas the alpha 2-adrenoceptor agonist UK 14304 (1.5 ng) significantly reduced the basal level of SDHACU; (2) none of the alpha-adrenoceptor antagonists used (phenoxybenzamine, 10 and 100 ng; BE 2254, 100 and 500 ng; yohimbine, 0.5 and 50 ng) significantly affected the basal level of hippocampal SDHACU, and only the alpha 1-adrenoceptor antagonist BE 2254 (500 ng) significantly reduced the testing-induced activation of SDHACU. Taken together, these findings suggest that noradrenaline may exert a bimodal regulatory influence on the activity of septo-hippocampal cholinergic neurons. The behavior-induced activation of hippocampal SDHACU could be partly mediated by the stimulation of alpha 1-adrenoceptors, whereas postsynaptic alpha 2-adrenoceptors may be important for the maintenance of a tonic inhibition of the steady-state cholinergic activity in the hippocampus.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic Agents↗

PubMed1994

Effects of anterior thalamic lesions on spatial memory in mice.

The present study was aimed at determining whether or not lesions of the anterior thalamic nuclei induced deficits in sequential or delayed spatial alternation (SA) in mice, these procedures enabling measures of sensitivity to interference and rate of forgetting respectively. Results showed that sequential SA comprising six successive trials separated by a 30 s inter-trial interval was not impaired by the lesion; in contrast, delayed SA in lesioned animals was impaired by a long (6 h) but not by a short (5 min) delay, compared with controls. These results support the view that lesions of anterior thalamic nuclei can produce anterograde amnesia for spatial informations selective to relatively long delay.

Animals↗

PubMed1994

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. In these conditions, our results showed that BALB/c mice evidenced better performance in retention than C57BL/6 mice after medial septal stimulation. On the other hand, the stimulation applied in resting conditions produced a moderate and similar hippocampal cholinergic activation in the two strains. Moreover, in BALB/c mice the only strain which exhibited good consolidation capacities the stimulation do not induced any additive effect on the substantial increase of the hippocampal cholinergic activity produced by the previous acquisition session. Finally, a correlative study realized in C57BL/6 mice seems to indicate that the higher the hippocampal cholinergic activity was the lower were the consolidation capacities. These results lead us to suggest that the improvement of memory consolidation induced by the medial septal stimulation is the consequence of the recruitment of non cholinergic elements located close to the electrode tip. Consequently the septo-hippocampal cholinergic activation is more likely to facilitate certain information processes prior to the consolidation mechanisms proper.

Animals↗

PubMed1994

Protein kinase C activity in the hippocampus following spatial learning tasks in mice.

Protein kinase C (PKC) is highly concentrated in the hippocampus and is thus a possible neural substrate of learning and memory. This study was designed to determine whether partial acquisition (i.e., the minimal amount of training leading to above-chance performance) of a spatial discrimination in an eight-arm radial maze alters hippocampal PKC activity. Mice were sacrificed at different times (5 minutes, 1 hour, 24 hours) after the second learning session, and PKC activity was measured in both cytosolic and membrane fractions of the hippocampus. In order to determine which component of the task was involved in the alterations in enzymatic activity, hippocampal PKC activity was also measured in a group of mice that was allowed to explore the maze freely. Significantly less PKC activity was found in the cytosolic fraction from the trained animals than from the quiet or active control groups. No differences were observed between the quiet and active controls. In contrast, there were no significant between-groups differences in membrane-bound PKC activity, although a negative correlation between the membrane-bound PKC activity and learning scores (accuracy) was noted. These results suggest that hippocampal PKC activity is involved essentially in the associative component of the task. The lack of learning-induced alterations in membrane-bound PKC activity and the negative correlation between this enzymatic activity and learning accuracy are discussed.

Animals↗

PubMed1994

Effects of intraseptally injected glutamatergic drugs on hippocampal sodium-dependent high-affinity choline uptake in "naive" and "trained" mice.

We have previously reported that spatial reference memory (RM) training-induced alterations in hippocampal cholinergic activity as measured by sodium-dependent high-affinity choline uptake (SDHACU). Each training session was found to induce an immediate (30 s) increase in SDHACU followed (30 s to 15 min posttest) by a deactivation and long-lasting inhibition (15 min to 24 h) of this cholinergic marker. The present experiments were designed to assess the role of septal glutamatergic receptors in this posttraining cholinergic deactivation. In the first experiment, the effects of intraseptal injections of different doses of glutamic acid and glutamatergic antagonists (kynurenic acid, KYN, and AP5) on hippocampal SDHACU were studied in awake but otherwise resting (i.e., naive) mice. The results showed that glutamic acid at the lowest dose used (5 ng) produced a decrease in SDHACU, whereas both glutamatergic antagonists produced a dose-related increase in this cholinergic marker. It was concluded that septal glutamatergic receptors mediate a tonic inhibitory input on the cholinergic cells. Hence, in a second experiment the effect of intraseptal injections of KYN (5 ng) on the training-induced changes in hippocampal cholinergic activity were assessed following variable amounts of radial maze RM training. Trained mice were injected 20 min before the first or the ninth training session and killed 30 s or 15 min posttraining for determination of SDHACU. KYN slowed the posttesting cholinergic deactivation (disinhibition), this effect being more marked in good learners than in bad learners. The present findings suggest that septal glutamatergic receptors mediate an inhibitory input on the cholinergic cells, and that this input could play a role in memory consolidation.

Animals↗

PubMed1994

[Hippocampus as interaction sites between cerebral memory systems].

Most of the current theories assume that there are multiple forms of memory that are supported by separate brain systems and have different characteristics. Animals studies on the various dual-memory theories have been carried out mainly on the basis of hippocampal system function. Specifically, they have focused on aspects of learning and memory that are impaired (vs. spared) by lesions of the hippocampal formation. However, there are several instances in the animal literature showing that hippocampal lesions actually produced enhanced learning and memory function. Moreover, the acquisition of tasks that are facilitated by hippocampal lesions (or dysfunction) is nevertheless associated, in intact subjects, with specific neurobiological alterations in the hippocampus. This problem has been analysed using two different tasks in mice: a bar-press conditioning and a spatial discrimination task. Results showed that, depending on the task considered, the same pharmacological treatment produced either a facilitation or an impairment of acquisition. Moreover, each task induced significant alterations in hippocampal adenylate cyclase activity but in opposite directions. Together with previous findings, these results suggest that the hippocampus is involved in both the so-called "hippocampal-dependent" and "hippocampal-independent" forms of memory. It is postulated that some of the observed training-induced neurobiological alterations might reflect the interaction between two (or more) competing memory systems at the hippocampal level. Thus, in addition to its proposed specific information processing functions (i.e., relational), the hippocampus would play a role in addressing information to the brain memory system that, in a given situation, has the best adaptive value.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗

PubMed1993

Spatial discrimination learning induces LTP-like changes in the lateral septum of mice.

The efficacy of synaptic transmission from the fimbria to the lateral septum (LS) of freely moving mice was monitored electrophysiologically over 9 days of training in a spatial discrimination task (radial maze). Electrical stimulation of the fimbria evoked two negative waves (N2 and N3) in the ipsilateral LS. Compared to a control group exposed to muscular effort (treadmill), trained animals displayed a significant and progressive increase in the amplitude of N3 with no changes in N2. Moreover, this increase was of greater magnitude in fast learners than in slow learners and persisted for at least 24 h following the last (9th) training session. These changes might play a role in spatial learning through the regulation of septohippocampal cholinergic activity.

Animals↗

PubMed1993

Relationships between testing-induced alterations of hippocampal cholinergic activity and memory performance on two spatial tasks in mice.

Alterations in hippocampal cholinergic activity associated with different types and/or stages of learning were explored using measures of sodium-dependent high-affinity choline uptake (SDHACU) in the hippocampus of C57BL/6 mice. Animals were divided into 'active' subjects submitted to memory testing before being killed and 'quite' controls. 'Active' subjects were trained in a radial-arm maze on either a discrimination task (mixed Working Memory (WM)-Reference Memory (RM) task) or a Delayed-Non-Matching-To-Place task (more selective WM-task). In the discrimination task mice were sacrificed after either the 1st, 2nd, 3rd or 9th daily session of training and at intervals of either 30 s, 15 min, 24 h or 9 days post-test. In the DNMTP-task all subjects of the 'active' groups were sacrificed after 12 days of training at either 30 s or 24 h post-test. Results showed that: (1) Both types of training induced an immediate (30 s post-test) increase of hippocampal SDHACU as compared to 'quite' control condition. (2) In the discrimination task, this immediate increase in SDHACU was followed by a decrease leading to a long-lasting (24 h and 9 days) inhibition of this cholinergic marker. This secondary decrease in SDHACU occurred earlier (15 min post-test) at the end (9th session) than at the beginning (1st-3rd sessions) of training. Thus, as training progressed there was a shortening of the testing-induced cholinergic activation. (3) By contrast, in the DNMTP-task, SDHACU was still increased at the interval of 24 h following the last session of DNMTP-training. (4) The amplitudes of both the immediate (30 s) increase and subsequent secondary (15 min) decrease in SDHACU after the last (9th) session of discrimination training were significantly related to the rate of acquisition and behavioural profile for individual animals. Subjects that had displayed better response accuracy across the 9 days of training exhibited the highest SDHACU at 30 s post-test and the lowest at 15 min post-test. These results are discussed in the context both of previous findings on the effects of training on cholinergic activity, and of contemporary models of hippocampal function. It is suggested that (1) an increase in hippocampal cholinergic transmission during testing would facilitate the acquisition of a 'relational' kind of informations (spatial WM and RM); (2) the post-training consolidation (spatial RM) of information would be facilitated by a decrease and long-lasting inhibition of hippocampal cholinergic activity.

Animals↗

PubMed1993

A comparative study of age-related changes in inhibitory processes and long-term potentiation in the lateral septum of mice.

Anaesthetized C57 BL/6 mice of different ages (young: 5 months; middle-aged: 15 months; and old: 21 months) were used to determine whether aging alters the efficiency of synaptic inhibition and long-term potentiation (LTP) in the lateral septum (LS). Electrical stimulation of the fimbria induced field potentials in the ipsilateral LS comprising two initial negative components (N2 and N3) followed by a positive wave of low amplitude. Paired-pulse experiments showed a facilitation of the N2 component and a concomitant depression of the N3 components. Facilitation of the N2 component was stronger in both middle-aged and old mice as compared to young mice, whereas an inverse pattern of changes was observed for inhibition of the N3 component. High-frequency stimulation of the fimbria produced a persistent increase in the N3 amplitude. This LTP was of significantly higher amplitude in both young and middle-aged mice as compared to old mice. These results suggest that aging impairs both inhibitory processes and synaptic plasticity in the mouse LS, but that inhibitory processes appear to be affected earlier.

Aging↗

PubMed1993

Role of the hippocampal formation in learning and memory.

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Hippocampus↗

PubMed1993

Extended temporal gradient for the retrograde and anterograde amnesia produced by ibotenate entorhinal cortex lesions in mice.

Effects of ibotenic entorhinal cortex (EC) lesions on both retrograde and anterograde amnesia in mice were assessed using two-choice discrimination tasks learned at different intervals before surgery in two eight-arm radial mazes. The results indicated that EC-lesioned mice were severely impaired in postoperative retention of discrimination problems learned 3 d or 2 weeks prior to surgery, but showed no deficit on problems learned between 4, and up to 6 weeks before surgery, as compared to sham-operated controls. When trained on a novel two-choice discrimination problem (not acquired preoperatively), experimental subjects demonstrated quite normal rates of acquisition, but were impaired in learning its reversal. Furthermore, they exhibited a faster rate of forgetting (anterograde amnesia) relative to controls over a 2-week retention interval. These results indicate that approximately 4 weeks is required before memory for a two-choice spatial discrimination problem no longer depends on the integrity of the entorhinal cortex, and suggests that, beyond this time, an EC-independent memory storage system is capable of supporting the retrieval of information. The data, together with complementary behavioral results, are discussed in the context of current theories of memory storage.

Amnesia↗

PubMed1992

Post-training medial septal stimulation improves spatial information processing in BALB/c mice.

The experiment reported here was designed to highlight the effects of medial septal nucleus electrical stimulation on memory processes. To that end, we have used a learning task carried out in a 4-hole board in which animals were successively presented with the location of 2 baited holes. Under these conditions, the consequence of a weak stimulation (30 microA peak to peak, 80 s in duration) applied 30 s after acquisition of these 2 separate spatial informations was assessed on a retention test 24 h later. The results indicated that performance of stimulated animals was improved by medial septal stimulation as shown by an increase in the time duration of exploration of the second previously baited hole. However, post-training stimulation also produced a significant avoidance of the first previously baited hole not observed in the control groups. These results suggest that medial septal stimulation improves retroactive inhibition involved in working memory processes, thus leading to better retention of this kind of learning situation.

Animals↗

PubMed1992

Memory deficits following chronic alcohol consumption in mice: relationships with hippocampal and cortical cholinergic activities.

Chronic ethanol consumption (12% v/v for 12 months) produced an accelerated decay of T-maze spontaneous alternation (SA) rates as the interval that elapsed between forced trials, used as acquisition, and a free test trial, used as a retention test, increased. Thus, alcohol-treated mice that exhibited normal SA rates at a short interval (5 min) were impaired at the longer one (6 h) relative to controls. This alcohol-induced deficit was almost completely reversed by physostigmine (0.05 mg/kg, IP) given only before the test trial. Parallel neurochemical analysis showed that chronic alcohol intake produced a significant decrease in hippocampal and cortical sodium-dependent high-affinity choline uptake. In particular, the significant cholinergic activation produced by a T-maze exploration in controls was attenuated in experimental subjects so that the between-groups differences already present in the quiet condition were amplified in the active (exploration) state. These findings suggest that the memory deficits induced by chronic ethanol consumption stem from a failure of some cholinergic-dependent retrieval processes. An attempt is made to relate the present results with our previous ones that emphasized the importance of diencephalic damage in alcohol-induced retrieval deficits.

Acetylcholine↗

PubMed1992

The hippocampo-septal projection in mice: long-term potentiation in the lateral septum.

In anaesthetized young mice, the fimbria was stimulated and field potentials were recorded ipsilaterally in the lateral septum (LS). Evoked responses were typically characterized by a two-component negative wave (N2 and N3) followed by a low amplitude positive wave. The amplitudes and latencies were highest and shortest respectively in the dorsal LS for the N3 component and in the ventral LS for the N2 component. Tetanic stimulation of the fimbria induced long-term potentiation (LTP) only in the case of the N3 component. The differential changes in N2 and N3 following tetanic fimbrial stimulation are discussed in the context that the dorsal LS appears to exhibit a higher density of LTP-mediating receptors.

Animals↗