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J Micheau

Publications and source records attributed to J Micheau.

At least 19 recordsLinked to original sources
PubMed2004

Reversible hippocampal inactivation partially dissociates how and where to search in the water maze.

To assess the interaction between spatial and procedural memory systems, the authors developed a learning protocol in the water maze using a rising "Atlantis" platform that requires rats to learn to swim to a specific location and, once there, to learn a "dwelling" response to raise the platform. In this protocol, the effects of temporal inactivation of the dorsal hippocampus with the AMPA/kainate receptor antagonist LY326325 on different memory phases were investigated. Hippocampal inactivation impaired acquisition of the searching task, mainly because of disruption of procedural learning. Inactivation also impeded consolidation and retrieval of spatial information, while leaving expression of dwelling responses intact. These findings challenge the idea of a sharp demarcation between spatial and procedural learning with respect to hippocampal involvement.

Animals↗
PubMed2001

Function of the hippocampus in memory formation: desperately seeking resolution.

Despite considerable efforts and successes investigating the function of the hippocampal formation in memory processes, there are still numerous elusive key issues. Some of them will be addressed in this review. We will argue that recent evidence supports hippocampal participation in several memory processes, such as encoding, short-term and long-term consolidation and retrieval. While some processes, for example encoding and short-term consolidation, have been the subject of detailed investigations, at least for specific and repeatedly used behavioural paradigms, there appears to be considerable lack of information with respect to other processes, for example long-term consolidation. Although the existence of long-term consolidation is not at debate here, there is only very fragmented information as to the cellular processes enabling long-term consolidation. Recent ample evidence now suggests a potential role in metabotropic glutamate receptors, and more specifically the phospholipase C-coupled receptor 5, in long-term consolidation. The hyperexpression of receptor protein was limited to CA1 indicating a specific role of this brain region in the consolidation of memories. Future work should further explore this important issue especially since long-term consolidation appears to be a necessity for permanent storage of information, and may thus engage memory mechanism that fail during ageing and dementia.

Animals↗
PubMed2001

Intrahippocampal injections of somatostatin dissociate acquisition from the flexible use of place responses.

Previous studies showed that injections of somatostatin (SS-14) into the hippocampus facilitate the acquisition of spatial tasks in mice. The present study was aimed at better understanding the learning and memory processes that could be affected by hippocampal SS-14 stimulation. Balb/c mice were submitted to a two-stage learning paradigm. In stage 1, they were trained for acquisition of a spatial discrimination task in a radial maze and, in stage 2, were submitted to a probe test aiming at evaluating their ability to use flexibly their previously acquired knowledge. Injections of vehicle or SS-14 were given during the acquisition phase and/or before the probe test using a 2 x 2 factorial design. Mice receiving SS-14 during acquisition failed to succeed in the probe test despite showing a trend to faster acquisition of the initial spatial discrimination task. By contrast, when given only prior to probe trials, SS-14 did not yield any behavioural effects. Thus, SS-14 interfered with the establishment of a flexible form of memory, not with its expression per se, and therefore dissociated the acquisition of place responses from their flexible use. The theoretical issues raised by the present findings are discussed.

Animals↗
PubMed2000

Calpain-PKC inter-relations in mouse hippocampus: a biochemical approach.

In previous studies, we isolated and identified a mu-calpain/PKCalpha complex from rabbit skeletal muscle. Here, we have used specific purification procedures in order to study the interactions between mu-calpain and PKC in mouse hippocampus, a brain structure implicated in memory processes. We observed that mu-calpain and conventional PKCs (alpha, betaII and gamma) are co-eluted after anion exchange chromatography. In contrast to our previous results obtained on skeletal muscle, mu-calpain and PKC isoenzymes were dissociated after gel filtration chromatography. Furthermore, mu-calpain induced the proteolytic conversion of PKCalpha, betaII, and gamma into PKMalpha, betaII, and gamma with a preferential hydrolysis of PKCgamma, a specific isoenzyme of the nervous system. Although the mu-calpain/PKC interactions in the hippocampus are quite different from skeletal muscle, our results however, point out the functional importance of these inter-relations. Moreover, as PKCgamma has been involved in the biochemical events underlying learning and memory, the preferential relationship between mu-calpain and PKCgamma promotes the importance of the role that mu-calpain could play in the cellular mechanisms of memory formation.

Animals↗
PubMed1999

Protein kinases: which one is the memory molecule?

Encoding of new experiences is likely to induce activity-dependent modifications in the brain. Studies in organisms far apart on the phylogenetic scale have shown that similar, sometimes identical, signal transduction pathways subserve plasticity in neuronal systems, and they may play pivotal roles in the formation of long-term memories. It has become evident that phosphorylation/dephosphorylation reactions are critical for the initiation of cellular mechanisms that embody, retain and modify information in neural circuits. Although physiological investigations on synaptic plasticity have had a major impact, we have concentrated our review on behavioural studies that provide direct or indirect evidence for a role of kinases in mechanisms underlying memory formation. From these, it appears that the learning event induces activation of a variety of kinases with specific time courses. For instance, the calcium/calmodulin-dependent protein kinase II seems to participate in an early phase of memory formation. Apparently, activation of both protein tyrosine kinases and mitogen-activated protein kinases is required for much longer and may thus have a particular function during transformation from short-term into long-term memory. Quite different time courses appear for protein kinase C (PKC) and protein kinase A (PKA), which may function at two different time points, shortly after training and again much later. This suggests that PKC and PKA might play a role at early and late stages of memory formation. However, we have considered some examples showing that these signalling pathways do not function in isolation but rather interact in an intricate intracellular network. This is indicative of a more complex contribution of each kinase to the fine tuning of encoding and information processing. To decipher this complexity, pharmacological, biochemical and genetic investigations are more than ever necessary to unravel the role of each kinase in the syntax of learning and memory formation.

Animals↗
PubMed1999

Intrahippocampal injections of cysteamine improve the retention of a bar-pressing task in mice.

Cysteamine was used as a tool aimed at investigating the role of central somatostatin (SS-14) and was shown to modulate learning in a task-dependent manner. However, direct arguments have not yet been provided to support the hypothesis that impairments and facilitation of learning produced by cysteamine are both mediated by the hippocampus. Mice were given daily intrahippocampal injections of artificial cerebrospinal fluid (CSF) or cysteamine at doses of either 2.5 microg/0.2 microl or 25 microg/0.2 microl 1 h prior to each learning session of a bar-pressing task, for which the acquisition was previously shown to be improved by systemic injections. The results showed that, with respect to CSF, the mice injected with cysteamine learned the bar pressing task faster whereas no evidence of changes in locomotor activity was provided. Moreover, the results showed that retention was specifically increased in the two groups injected with cysteamine. It is argued that the action of cysteamine on the hippocampus is sufficient to modulate specifically learning-memory processes in a task-dependent manner. In conclusion, the blockade of some hippocampal information processing function by cysteamine is discussed to understand the bidirectional effects of drugs on learning and memory.

Animals↗
PubMed1999

Stimulation of 5-HT1A receptors by systemic or medial septum injection induces anxiogenic-like effects and facilitates acquisition of a spatial discrimination task in mice.

1. In the present study, the authors addressed the issue of the possible modulation of both emotional and learning processes by the stimulation of 5-HT1A receptors. In this respect, we have carried out two series of experiments: the first series examined the effects of systemic injections of 8-OH-DPAT, a 5-HT1A receptor agonist, successively on a model of anxiety and on a learning task; secondly the effects of selective infusions into the medial septum were studied in the same experimental design. 2. Mice were tested in an elevated plus-maze before being submitted to a spatial discrimination task in an 8-arm radial maze. The 8-OH-DPAT (1 mg/kg) administered intraperitoneally 30 minutes prior to testing, induced anxiogenic-like effects in the plus-maze and improved the acquisition of the spatial discrimination. 3. Moreover, a regression analysis showed that the index of anxiety measured in the elevated plus-maze was positively correlated with the performance level reached at the forth day of training in the spatial discrimination task. The intraseptal infusion of the drug (1 microgram) demonstrated the same pattern of results, although the effects were less pronounced. Again a correlation between the index of anxiety and acquisition performance was obtained. 4. These results suggest that anxiogenic-like effects induced by selective stimulation of 5-HT1A receptors have a positive influence on the acquisition of a memory task. As systemic injections appeared to be more effective than intra-septal infusions, these effects might be mediated by both pre- and postsynaptic 5-HT1A receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1999

Reversible neural inactivation reveals hippocampal participation in several memory processes.

Studies of patients and animals with brain lesions have implicated the hippocampal formation in spatial, declarative/relational and episodic types of memory. These and other types of memory consist of a series of interdependent but potentially dissociable memory processes-encoding, storage, consolidation and retrieval. To identify whether hippocampal activity contributes to these processes independently, we used a novel method of inactivating synaptic transmission using a water-soluble antagonist of AMPA/kainate glutamate receptors. Once calibrated using electrophysiological and two-deoxyglucose techniques in vivo, drug or vehicle was infused chronically or acutely into the dorsal hippocampus of rats at appropriate times during or after training in a water maze. Our findings indicate that hippocampal neural activity is necessary for both encoding and retrieval of spatial memory and for either trace consolidation or long-term storage.

Animals↗
PubMed1998

Cytosolic hippocampal PKC and aging: correlation with discrimination performance.

Adult and aged mice were submitted to a discrimination task in a radial maze (regular trials), and then to probe trials requiring them to form relational representations. Three weeks later, animals were again tested for regular and probe trials. Following another interval of 3 weeks, individual hippocampal cytosolic calcium-dependent and -independent PKC activities were measured. Performance of aged animals was impaired on probe but not regular trials and aged mice had lower hippocampal cytosolic calcium-dependent and -independent PKC activities than adults. Performance on probe trials was specifically correlated with calcium-dependent PKC activity. This suggests a specific relationship between the ability to form relational representations and hippocampal cytosolic calcium-dependent PKC activity.

Aging↗
PubMed1998

The opposite effects of cysteamine on the acquisition of two different tasks in mice are associated with bidirectional testing-induced changes in hippocampal adenylyl cyclase activity.

The hypothesis of a role for hippocampal somatostatin (SS-14) in learning and memory processes was further examined by means of 2 selective learning tasks that were previously shown to be either impaired (spatial discrimination task) or facilitated (barpressing task) by hippocampal lesions. Results showed that subcutaneous injections of cysteamine (160 mg/kg) (a) impaired acquisition of the spatial task while producing an opposite (i.e., facilitative) effect on acquisition of the barpressing task and (b) produced an up regulation of hippocampal adenylyl cyclase (AC) activity, which was antagonized by spatial discrimination training but enhanced by training in the barpressing task. Moreover, opposite task-dependent training-induced changes in hippocampal AC activity was observed in saline-treated mice. These results suggest that bidirectional regulatory mechanisms of hippocampal function involving both SS-14 and ACs may occur as a function of the type of learning.

Adenylyl Cyclases↗
PubMed1996

Investigations on the role of hippocampal protein kinase C on memory processes: pharmacological approach.

We report here investigations on the functional involvement of hippocampal protein kinase C (PKC) in learning and long-term retention of spatial discrimination in a radial maze. A pharmacological approach was employed to test the behavioural effects of intrahippocampal injections of drugs that either activate or inhibit PKC activity. Mice with intrahippocampal guide cannula were trained in a mixed spatial reference-working memory task during 7 daily sessions. Sixteen days later, the animals were submitted to a retention session. In the first experiment, the animals were treated before each learning session with polymyxin B (PMB, a PKC inhibitor) and their scores were compared to those of an appropriate control group. In the second experiment, a group received the injection of 1-oleoyl-2-acetyl glycerol (OAG, a PKC activator) before and after the 7th learning session in order to test the effect of activation of PKC on long-term retention. The results showed that: (1) PMB administration delayed the acquisition of the reference memory component of the task, whereas long-term retention appeared to be improved; and (2) administration of OAG at the end of the acquisition phase improved long-term retention. Neither PMB nor OAG appeared to affect working memory. Taken together, the results point to an involvement of hippocampal PKC in the acquisition of information destined for long-term storage.

Animals↗
PubMed1995

Glucose enhancement of scopolamine-induced increase of hippocampal high-affinity choline uptake in mice: relation to plasma glucose levels.

The administration of glucose has been shown to improve memory for various learning tasks in rodents. In humans, glucose also increases declarative memory performance in elderly people and in some patients with mild Alzheimer's disease. One of the possible physiological bases for the effect of glucose on memory processes is a facilitation of cholinergic function through increased synthesis. In support of this hypothesis, glucose was shown to attenuate the amnesia induced by scopolamine and, in similar conditions, glucose increased extracellular levels of acetylcholine following a scopolamine injection. To further examine the interaction between glucose and cholinergic function, the present experiment measured the effects of combined injections of glucose and scopolamine on hippocampal sodium-dependent high-affinity choline uptake, an indirect index of cholinergic activity. Results showed that the injection of 3 g/kg glucose enhanced the increase in high affinity choline uptake in hippocampal synaptosomes produced by scopolamine. A regression analysis revealed the existence of a positive correlation between plasma blood glucose level and hippocampal choline uptake particularly in the animals receiving a combined injection of scopolamine and glucose. These data further support the hypothesis that glucose administration can facilitate acetylcholine synthesis under certain conditions and that this action could explain how glucose attenuates scopolamine-induced amnesia.

Analysis of Variance↗
PubMed1995

Alteration of cortical and hippocampal cholinergic activities following lesion of the mammillary bodies in mice.

The effects of ibotenic acid lesions of the mammillary bodies (MM) on the sodium-dependent high affinity choline uptake (SDHACU) velocity into both the hippocampus and the frontal cortex were investigated in this study in either a quiet or an active (exploration of a T-maze) condition. Results showed that MM lesion globally produced a significant decrease of both hippocampal and cortical SDHACU. However, the magnitude of this decrease was not significantly different in the active as compared to the quiet condition. These findings suggest that MM lesion alters the tonically but not phasically active transynaptic control of cortical and hippocampal cholinergic activities.

Acetylcholine↗
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

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↗