Biomedical subjects

R Jaffard

Publications and source records attributed to R Jaffard.

At least 91 records · Page 5Linked to original sources

PubMed1989

The durations of hippocampal and cortical cholinergic activation induced by spatial discrimination testing of mice in an eight-arm radial maze decrease as a function of acquisition.

Sodium-dependent high-affinity choline uptake velocities in P2 fractions of the hippocampus and cortex of mice were analyzed at different times following both the first (Day 1) and last (Day 9) daily sessions of a spatial discrimination testing procedure in an eight-arm radial maze. Results showed that the immediate (30 s) post-training increase in mean hippocampal and cortical cholinergic activity observed on Day 1 did not significantly vary over days despite a marked and progressive improvement of discrimination performance. In contrast, the duration of these activations was considerably shortened in both structures between Days 1 (more than 1 hr) and 9 (about 15 min). The possible involvement of these changes in memory consolidation processes is discussed.

Animals↗

PubMed1989

Effects of anterior or dorsomedial thalamic ibotenic lesions on learning and memory in rats.

Sprague-Dawley rats were used to study the effects of ibotenic acid lesions of the anterior (A.Th.) and the dorsomedial (MD) thalamic nuclei on learning and memory. Memory was assessed by employing a temporal alternation task in a straight alley with varying intertrial intervals. In addition, spatial orientation and response flexibility were evaluated on a radial maze and on a spatial reversal task (SSDR). The results indicated that MD rats required more trials to learn the temporal alternation task and exhibited impaired performance compared to A.Th. and control groups at the shortest delay (15 s). In contrast, compared to the control group, A.Th. subjects which required less trials to master the task and exhibited normal performance at the 15-s delay were impaired when the intertrial interval was increased to 45 s. Whatever the lesion, no impairments were found in the SSDR or the radial maze while only MD lesions were found to result in a night hyperactivity associated with greater food and water consumptions. These findings indicate that A.Th. and MD are differentially involved in learning and memory processes. It is suggested that the MD is mostly involved in registering new information while the A.Th. plays a role in the maintenance of information over time.

Animals↗

PubMed1989

[P 300 wave and additive or self-terminated processes in short-term image recognition].

The study of the P 300 wave during the acquisition and the recognition of simple symbolic pictures shows a self-terminated treatment in short-term visual recognition processes. The results of this study plead in favour of a general principle of psychobiological economy and of a decrease of the mental charge. This principle is at variance with one of the postulates of Sternberg's additive processes theory.

Adult↗

PubMed1989

Experimental dissociation of memory systems in mice: behavioral and neurochemical aspects.

Evidence for different types of memory in mice may lead to development of animal models for human memory disorders and provides informations on neurobiological systems underlying these processes. Series of experiments in mice, using a 8-arm radial maze with or without cholinergic drugs or chronic alcohol consumption supply arguments for multiple memory stores and for cholinergic influence greatest for short-term system. Studies of differential cholinergic activation following training militate for dissociation in time of hippocampal and cortical cholinergic pathways. Age-related memory involvement seems to be associated with an attenuation of central cholinergic activation. Several problems inherent to sensitivity and selectivity of the tasks remain in discussion.

Animals↗

PubMed1988

Differential hippocampal and cortical cholinergic activation during the acquisition, retention, reversal and extinction of a spatial discrimination in an 8-arm radial maze by mice.

Possible differentiation of the intervention of cholinergic septohippocampal and magnocellular forebrain (NBM) projections to cortex during learning and memory processes has been investigated directly using mice. High-affinity choline uptake velocities in the hippocampus and cortex were analyzed, in parallel, at various periods during the acquisition, over 8 days, as were the subsequent retention, reversal and extinction of a spatial discrimination in an 8-arm radial maze. Initial acquisition induced an immediate (30 s) and long-lasting (approx. 3 h) increase in mean hippocampal (+33%) and cortical (+23%) cholinergic activities. The time course of this activation was structure-dependent and correlations of hippocampal-cortical cholinergic activities showed large and consistent alterations as a function of time after training. Cholinergic activation in both brain regions was observed immediately following each daily training session with amplitudes which did not vary significantly in spite of a progressive daily increment in performance. Following acquisition mice were tested for retention, reversal and extinction: 30 s following the retention session, cholinergic activation was observed in both cortex and hippocampus, with magnitudes similar to those observed at the end of acquisition. However, in the reversal and extinction groups, a treatment-dependent attenuation of cholinergic activation was observed which was accompanied by a significant loss of correlation of cholinergic activity between these two brain regions. The results are discussed in relation to the concepts of reference and working memory and also to novelty, stress, arousal and frustrative non-reward. The data constitute direct experimental evidence for a differential involvement of cholinergic septohippocampal and NBM-cortical projections in learning and memory processes.

Animals↗

PubMed1987

The effect of diazepam on hippocampal EEG in relation to behavior.

Male mice of the BALB/cByJ and C57BL/6 strains were implanted with electrodes in the CA1 area of the hippocampus to record rhythmic slow-wave activity (RSA) or 'theta' EEG activity. The EEG spectral characteristics and the animal's motor behavior were studied while the animals walked on a moving belt (2.2 cm/s) both before and after i.p. injections of diazepam (Valium, 2 mg/kg) or vehicle. EEG spectral analyses were carried out on-line by computer. Diazepam produced a dissociation of locomotion and RSA. (1) Uninjected and vehicle-injected mice showed typical RSA (7-8 Hz) while walking. (2) Under diazepam, 7-8 Hz RSA virtually disappeared and was replaced in the temporally averaged records by RSA with a sharp, narrow-band peak at 4-5 Hz. (3) This lower-frequency RSA was associated with immobility if, and only if, the immobility immediately followed walking. This was true whether the animal itself stopped walking or the experimenter stopped the moving belt. This theta activity predominated for about 30 s and had disappeared after 2 min. Locomotion, on the other hand, was accompanied by irregular EEG activity. (4) Scopolamine (i.p. 1 mg/kg), a cholinergic blocker, greatly reduced the diazepam-induced 4-5 Hz RSA, but also partially restored 7-8 Hz RSA. The possibility that the effects of diazepam on hippocampal EEG involve changes in septohippocampal cholinergic activity is discussed.

Animals↗

PubMed1987

Neuroanatomical effects of chronic ethanol consumption on dorsomedial and anterior thalamic nuclei and on substantia innominata in mice.

Quantitative analysis, using histological sections, showed that chronic ethanol consumption for 7 months produced a weak but significant cellular loss in the dorsomedial thalamic nucleus, anterior thalamus and substantia innominata in the mouse. These results are in agreement with patterns of neuroanatomical damage observed in human alcoholics.

Animals↗

PubMed1987

Build-up and release from proactive interference during chronic ethanol consumption in mice: a behavioral and neuroanatomical study.

Male mice of the BALB/c strain were given a solution of 15% ethanol as their only source of fluid during either 24 or 48 weeks. They were submitted to a sequential alternation (SA) task in a T-maze (6 successive trials). It was found that 48 but not 24 weeks of alcohol administration lead to a deficit as compared to pair-fed or tap-water controls. Whereas experimental mice performed as well as controls on the first 3 choices, they exhibited a gradual decrease in the SA rate on subsequent trials. We suggest that this deficit might result from an exaggerated vulnerability to proactive interference (PI). In order to further test this hypothesis, a second experiment investigated whether a between-trials variation of context of the maze would increase performance. It was found that the SA rate improved as soon as the variation was provided (5th trial). We suggest that the deficit of experimental mice results from an impairment of retrieval processes. A neuroanatomical study was conducted to quantify cell losses resulting from 8, 24 or 48 weeks of ethanol treatment in the mammillary bodies (MM) or the hippocampus (HPC). At the time of appearance of the deficit, MM exhibited a -32% cellular loss, whereas this was only -18% in the HPC. This result emphasises the importance of MM lesion in memory deficits resulting from long-term alcohol consumption.

Alcohol Amnestic Disorder↗

PubMed1987

Impairment of spontaneous alternation behavior in sequential test procedures following mammillary body lesions in mice: evidence for time-dependent interference-related memory deficits.

The experiments reported here examined the effects of either radio frequency or kainic acid lesions of the median mammillary nucleus (MM) on spatial spontaneous alternation (SA) in mice. Animals were tested in a T-maze with sessions of six to nine successive trials given at varying intertrial intervals (ITIs). In the first experiment, conducted with an ITI of 30 s, damaged animals exhibited normal rates of SA on the second trial of the session but were progressively impaired on subsequent trials compared with controls. This finding was interpreted as an increased vulnerability to proactive interference. The second experiment was designed to investigate the effect of the ITI, and the results indicated that the previously observed impairment was completely suppressed by reducing the ITI from 30 s to 5 s. In order to further test our interference hypothesis, a third experiment was designed to investigate whether providing the animals with an extrinsic cue on one trial (5th) would increase the rate of SA on the subsequent (6th) trial (release from interference). Unexpectedly, results from this experiment showed that performance dramatically improved as soon as the cue was provided (i.e., on the 5th trial). These results are discussed in relation to a possible role of the mammillary bodies in memory processes. Specifically, it is suggested that as for Korsakoff patients, MM damaged mice suffer from an impaired ability to make temporal order judgments. Thus changing the context serves to help the animal actively reconstruct the sequence of past events.

Animals↗

PubMed1986

The effects of acute intraseptal injection of haloperidol in vivo on hippocampal cholinergic function in the mouse.

Acute injection of haloperidol into the lateral septum in mice produced an immediate and long-lasting increase in hippocampal sodium-dependent high-affinity choline uptake. Parallel electrophysiological investigations revealed that the increased septo-hippocampal cholinergic activity augmented CA1 pyramidal cell excitability and also accelerated the extinction of a conditioned reinforcement. These results constitute further evidence that septal dopaminergic terminals, via their control of septo-hippocampal cholinergic activity play a significant role in the modulation of hippocampal function.

Animals↗

PubMed1986

On the involvement of the central cholinergic system in memory deficits induced by long term ethanol consumption in mice.

Male mice of the BALB/c strain were given a solution of 12% v/v ethanol as their only source of fluid for 7 months. Memory performance was tested after ethanol was omitted from the diet for 3 to 9 weeks, and was compared with performance of control animals (no ethanol) which had been pair-fed or had received tap water. The spontaneous alternation task that was used consisted of two forced trials (acquisition) followed, at varying intervals ranging from 30 sec to 6 hr, by a free test trial (retention). Experimental subjects exhibited an accelerated rate of decay of spontaneous alternation, reaching chance level at 6 hours. All animals were then tested at this 6-hour interval following injections of either physostigmine or neostigmine that were given before both acquisition and retention (0.05 mg/kg IP). Results showed that physostigmine, but not neostigmine, dramatically improved performance of alcohol-treated subjects. Parallel neurochemical analysis showed that chronic ethanol treatment induced a slight (12%) but significant decrease in hippocampal sodium-dependent high affinity choline uptake. Though these findings suggest that the observed memory deficits (i.e., an accelerated rate of forgetting) might be related to a cholinergic dysfunction, alternative explanations are also proposed.

Alcoholism↗

PubMed1985

Facilitation of spontaneous and learned spatial behaviours following 6-hydroxydopamine lesions of the lateral septum: a cholinergic hypothesis.

Mice received injections of 6-hydroxydopamine (6-OHDA) in the lateral septum; they were tested for spontaneous alternation, acquisition and reversal of a spatial discrimination in a T-maze. In each of these tasks, performance of 6-OHDA lesioned mice was improved relative to controls. Neurochemical analysis revealed that 6-OHDA lesioned mice exhibited a significant increase in the rate of sodium-dependent high affinity choline uptake in the hippocampus. These results are discussed in relation to current theories concerning the role of the septo-hippocampal complex and cholinergic system in the control of behaviour.

Animals↗

PubMed1985

Chronic administration of sulbutiamine improves long term memory formation in mice: possible cholinergic mediation.

Thiamine deficiency in both man and animals is known to produce memory dysfunction and cognitive disorders which have been related to an impairment of cholinergic activity. The present experiment was aimed at testing whether, inversely, chronic administration of large doses of sulbutiamine would have a facilitative effect on memory and would induce changes in central cholinergic activity. Accordingly mice received 300 mg/kg of sulbutiamine daily for 10 days. They were then submitted to an appetitive operant level press conditioning test. When compared to control subjects, sulbutiamine treated mice learned the task at the same rate in a single session but showed greatly improved performance when tested 24 hr after partial acquisition of the same task. Parallel neurochemical investigations showed that the treatment induced a slight (+ 10%) but significant increase in hippocampal sodium-dependent high affinity choline uptake. The present findings and previous results suggest that sulbutiamine improves memory formation and that this behavioral effect could be mediated by an increase in hippocampal cholinergic activity.

Animals↗

PubMed1985

Memory deficits subsequent to chronic consumption of alcohol in mice: an analysis based on spontaneous alternation behavior.

Male mice of the BALB/c strain were given a solution of 15% ethanol as their only source of fluid for periods varying from 5 weeks to 8 months. For behavioral testing, they were compared with control groups which had received either an isocaloric solution of sucrose or tap water. Memory was tested by using spontaneous alternation behavior in a T maze. Each test consisted of two forced trials (acquisition) followed by a free trial (test) given at different acquisition--test intervals (from 30 s to 24 h). Results from two independent experiments showed that after 25 weeks of ethanol administration there was an accelerated rate of decay of spontaneous alternation as a function of the acquisition--test interval. Such a phenomenon persisted after ethanol was omitted from the diet. A third experiment showed that when tested on two successive sessions separated by a 5 h interval, experimental subjects exhibited a decreased ability to perform normally on the second test. Our data are interpreted as showing that long-term ethanol administration results in accelerated forgetting and increased vulnerability to proactive interference and, as such, they are compared to the memory dysfunctions observed in amnesic patients.

Alcohol Drinking↗

PubMed1985

Physostigmine reverses memory deficits produced by pretraining electrical stimulation of the dorsal hippocampus in mice.

The aim of the present experiments was to test the validity of the hypothesis that presynaptic cholinergic activity has a functional significance for memory formation. The results show that electrical stimulation of the dorsal hippocampus delivered before learning in BALB/c mice which induces a decrease of about 40% in hippocampal choline acetyltransferase (ChAT) activity at the time of learning results in deficits in retention scores in two appetitive learning tasks (operant conditioning in the Skinner box or a spatial memory task using a 4-hole board). In both behavioral tasks intraventricular injection of 1 microgram of physostigmine 20 min before the acquisition session reverses the disruptive effect of pretraining hippocampal stimulation. Our results seem to indicate that the memory deficits produced by pretraining electrical stimulation of the hippocampus result from both a decrease in ChAT activity and a corresponding reduction of acetylcholine availability in the hippocampal formation.

Acetylcholine↗

PubMed1984

Chronic ethanol consumption induces neuronal loss in mammillary bodies of the mouse: a quantitative analysis.

Quantitative analysis, using histological sections, showed that chronic ethanol consumption in the mouse produced neuronal loss in the medial mammillary bodies. This cellular loss was not uniform and was more marked in posterior (-30.1%) than in anterior (-8.8%) parts. Moreover, a reduction of the nucleus diameter of the remaining neurons was found. These results are in agreement with patterns of neuroanatomical damage observed in human alcoholics.

Alcoholism↗

PubMed1984

[Improvement in spontaneous and acquired spatial behaviors following lesions of septal dopaminergic afferents in mice: possible relations with hippocampal cholinergic activity].

Recent evidence from pharmacological studies support the view that dopaminergic afferents to the septal complex which originate from the mesencephalic A10 area, exert a tonic inhibitory control over the activity of the septal-hippocampal cholinergic neurons. Accordingly one could predict that the release from such an inhibition by lesion of the septal dopaminergic terminals might improve performance in tasks known to be related to hippocampal cholinergic activity. In order to test this hypothesis mice of the C57BL/6 strain received a bilateral injection of 6-hydroxydopamine in the lateral septal nucleus; they were compared to subjects receiving saline and to unoperated control mice in tests performed in a T-maze: spontaneous alternation, acquisition and reversal of spatial discrimination. In all tasks, performance of experimental subjects was improved relative to controls. However, subsequent experiments showed that this improvement was not observed when visual (light/dark) discrimination was used. Finally, 6-hydroxydopamine injected mice exhibited a substantial increase in hippocampal sodium-dependent high affinity choline uptake (+ 16.7%). These results are discussed in relation to the three main theories concerning the role of the septo-hippocampal complex and cholinergic system in the control of behavior (i.e. Pavlovian internal inhibition, spatial mapping and working memory). Only the theory of spatial cognition seems to account for our present findings.

Afferent Pathways↗

PubMed1983

Influence of the medial septal nucleus on the excitability of the commissural path-CA1 pyramidal cell synapse in the hippocampus of freely moving mice.

Changes in the excitability of the commissural path-CA1 pyramidal cell synapse were studied by varying the interval between the application of a conditioning pulse in the medial septal nucleus and a test pulse in the contralateral hippocampus in freely moving mice. The results showed that septal prestimulation results in marked changes in the excitability of pyramidal cells (population spikes) without any associated changes in the averaged evoked excitatory post synaptic potentials. Thus, as a result of septal stimulation, population spikes were first potentiated for interpulse intervals ranging from 10 to 30 ms; this was followed by inhibition at intervals between 40 and 60 ms and then by another phase of hyperexcitability between 100 and 160 ms. Possible mechanisms underlying this phenomenon are discussed and these successive changes in excitability are compared to the phase-locked ones which occur spontaneously during theta waves.

Afferent Pathways↗