Search PubMed⌕ Search

Biomedical subjects

G Riedel

Publications and source records attributed to G Riedel.

At least 19 recordsLinked to original sources

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↗

Elements of a neurobiological theory of the hippocampus: the role of activity-dependent synaptic plasticity in memory.

The hypothesis that synaptic plasticity is a critical component of the neural mechanisms underlying learning and memory is now widely accepted. In this article, we begin by outlining four criteria for evaluating the 'synaptic plasticity and memory (SPM)' hypothesis. We then attempt to lay the foundations for a specific neurobiological theory of hippocampal (HPC) function in which activity-dependent synaptic plasticity, such as long-term potentiation (LTP), plays a key part in the forms of memory mediated by this brain structure. HPC memory can, like other forms of memory, be divided into four processes: encoding, storage, consolidation and retrieval. We argue that synaptic plasticity is critical for the encoding and intermediate storage of memory traces that are automatically recorded in the hippocampus. These traces decay, but are sometimes retained by a process of cellular consolidation. However, we also argue that HPC synaptic plasticity is not involved in memory retrieval, and is unlikely to be involved in systems-level consolidation that depends on HPC-neocortical interactions, although neocortical synaptic plasticity does play a part. The information that has emerged from the worldwide focus on the mechanisms of induction and expression of plasticity at individual synapses has been very valuable in functional studies. Progress towards a comprehensive understanding of memory processing will also depend on the analysis of these synaptic changes within the context of a wider range of systems-level and cellular mechanisms of neuronal transmission and plasticity.

Animals↗

Functions of cannabinoid receptors in the hippocampus.

Marijuana smoking is recognised to impair human cognition and learning, but the mechanisms by which this occurs are not well characterised. This article focuses exclusively on the hippocampus to review the effects of cannabinoids on hippocampal function and evaluate the evidence that hippocampal cannabinoid receptors play a role in learning and formation of memory. Activation of cannabinoid receptors inhibits release of a variety of neurotransmitters, and modulates a number of intrinsic membrane conductances. Suppression of inhibitory GABAergic synaptic transmission has been repeatedly described, but whether there is also control of excitatory glutamatergic transmission is more controversial. The recognition that the commonly used WIN55,212-2 also acts via non-cannabinoid receptors may help resolve this issue. The involvement of endocannabinoids in depolarisation induced suppression of inhibition (DSI) and the demonstration that activation of metabotropic glutamate receptors can stimulate endocannabinoid release have provided the first insights into the physiological roles of the cannabinoids. Cannabinoids have consistently been reported to inhibit high frequency stimulation induced synaptic long-term potentiation but the experimental design of most behavioural experiments have meant it is not possible to categorically demonstrate a role for hippocampal cannabinoid receptors in learning and memory.

Animals↗

Aluminium toxicity in the rat brain: histochemical and immunocytochemical evidence.

Although the neurotoxic actions of aluminium (Al) have been well documented, its contribution to neurodegenerative diseases such as Alzheimer's disease remains controversial. In the present study, we applied histochemical techniques to identify changes induced by intracerebroventricular Al injections (5.4 microg in 5.5 microl, daily over a period of 5 successive days) in the adult rat brain after survival periods of either 1 or 6 weeks. For both Al- and saline-infused controls, no major signs of gross histological changes were evident in cresyl violet-stained sections. Al (as indicated by the fluorescent Morin staining) was concentrated in white matter of the medial striatum, corpus callosum, and cingulate bundle. Immunoreactivity of astrocytes and phagocytic microglia based on glial fibrillary acidic protein and ED1 markers, respectively, revealed a greater inflammatory response in Al-injected animals compared to controls. Damage of the cingulate bundle in Al-treated animals led to a severe anterograde degeneration of cholinergic terminals in cortex and hippocampus, as indicated by acetylcholinesterase labelling. Our data suggest that the enhancement of inflammation and the interference with cholinergic projections may be the modes of action through which Al may cause learning and memory deficits, and contribute to pathological processes in Alzheimer's disease.

Acetylcholine↗

Visual discrimination learning in the water maze: a novel test for visual acuity.

Learning about space, the environment and specific objects comprising three-dimensional arrangements requires processing of visual information. As learning and memory experiments in mammals rely heavily on normal processing of visual cues, drug-induced disruption of acquisition learning or memory formation necessitates the important control for visual acuity. A popular task used frequently for rats is the Morris water maze. However, previously used visual tasks in the water maze only control for gross visual disturbances. Here we describe a new training procedure enabling visual acuity to be tested in the water maze. Animals were trained to discriminate between two cue cards containing a pattern of vertical black and white stripes. Cards were presented in two adjacent quadrants separated by a barrier with the escape platform located in front of the smaller stripes (1 cm wide). Once 80% correct responses were attained, the wider cue card (normally 5 cm wide stripes) was randomly changed to gratings of 1,2,3,4,5, and 10 cm width. Animals learned the discrimination with acuity of 1.5 c/deg. A detailed analysis of the swim patterns further suggests that, independent of the grating used, animals make a choice immediately after release and swim along the walls towards the cue. In a further acuity test taken a few weeks later when animals were given saline infusions, performance was better than in the first test suggesting an effect of learning. This novel test may prove useful in determining subtle drug-induced deficits in visual acuity that may contribute to disruption of spatial performance in the water maze.

Animals↗

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↗

Hematogenous cervical spondylodiscitis after severe burn injury.

A 47-year-old man sustained a 31% TBSA burn injury. In spite of early escharectomy and mesh-graft-transplantation the patient suffered a septicaemic phase in the first week, which was treated by a specific antibiotic. Five weeks after the burn injury a cervical spondylodiscitis was diagnosed. Immediate wound debridement, ventral and dorsal spondylodesis with a tricortical bone-graft from the left iliac crest and titanium plates and specific antibiotic therapy led to the stabilization and healing of the cervical spinal column. The spondylodiscitis was microbiologically proved to be hematogenous after spread of Staphylococcus aureus from the blood in the early septicaemic phase. Swab culture from the burn surface wound, infected vertebrae and blood during the septicaemic phase revealed coagulase positive S. aureus. The aetiology, predisposing factors and management of this rare, but recognized, complication of major burns are discussed. Case features of this patient are compared with the single site's reported case of hematogenous cervical spondylodiscitis after severe burn injury.

Anti-Bacterial Agents↗

Fear conditioning-induced time- and subregion-specific increase in expression of mGlu5 receptor protein in rat hippocampus.

Memory formation involves encoding, consolidation and retention. These processes have been the subjects of considerable research, but physiological mechanisms underlying consolidation have proved difficult to dissociate experimentally. Previous reports have indicated a role for metabotropic glutamate receptors (mGluRs) in memory formation, and we here examined the specific role of mGluRs in the consolidation phase of memory formation. Particular weight was given to the hippocampus due to a high expression level for group I mGluRs and its outstanding role in spatial learning. Rats were first trained in a combined context and cue conditioning paradigm. Then, ex vivo analysis of neuronal tissue taken from hippocampal CA1, CA3 or dentate gyrus of behaviourally trained animals showed a 3-fold hyper-expression of mGluR5 protein in CA3 one day after acquisition training. This increase was transient and greatly diminished within ten days. The decline was paralleled by an increase in mGluR5 protein expression in CA1 and, to a lesser extent, in dentate gyrus, ten days posttraining. Overexpression in CA1 was also obtained after 9 days of extinction training. These data provide new insight into the role of the hippocampus and its subregions in memory consolidation. They support the notion that mGluRs in CA3 may play a part in short-term, and those in CA1 may play a part in long-term consolidation of memory.

Animals↗

Activation of nicotinic acetylcholine receptors patterns network activity in the rodent hippocampus.

1. Intracellular and extracellular recordings from area CA3 of rat and mouse hippocampal slices revealed two distinct modes of synchronous network activity in response to continuous application of muscarinic acetylcholine receptor (mAChR) agonists. At low concentrations (e.g. 0.1-1 microM oxotremorine-M), 'burst-mode' activity comprised regular individual AMPA receptor-mediated depolarizing events, each generating several action potentials. At higher concentrations (5-50 microM), 'theta-mode' prevailed in which ordered clusters of depolarizing theta-frequency oscillations occurred. 2. Whilst theta-mode activity was abolished by the mAChR antagonist atropine (5 microM), the nicotinic acetylcholine receptor (nAChR) antagonists tubocurarine (100 microM), mecamylamine (100-500 microM) and dihydro-beta-erythroidine (250 microM) converted this mode of activity to burst-mode. 3. Likewise, disruption of synaptically available ACh using inhibitors of choline uptake (hemicholinium-3; 20-50 microM) or vesicular ACh transport (vesamicol; 50 microM) converted theta-mode into burst-mode activity. 4. Hippocampal slices prepared 2-3 weeks after transection of the primary cholinergic efferent pathway from the medial septum exhibited reduced vesicular ACh transporter immunoreactivity but still supported nAChR-dependent theta-mode activity suggesting that ACh released from this pathway was not critical for the activation of these receptors. 5. In summary, ACh-mediated activation of nAChRs tailors the pattern of network activity into theta-frequency depolarizing episodes as opposed to synchronized individual events at much lower frequencies.

Animals↗

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↗

If phosphatases go up, memory goes down.

Previous work has provided conclusive support for a role of various protein kinases in processes underlying learning and memory formation. While these processes are not yet established in full detail, it is interesting to entertain the idea of protein phosphatases being involved in such mechanisms as well. Recent advances in this respect have provided preliminary support of this view. From the pharmacological as well as the transgenic analysis, it appears that especially the calcineurin/inhibitor-1 cascade plays an important role in the transition of intermediate-term into long-term memory formation.

Animals↗

Task-specific enhancement of short-term, but not long-term, memory by class I metabotropic glutamate receptor antagonist 1-aminoindan-1,5-dicarboxylic acid in rats.

Pharmacological application of broad agonists and antagonists has supported the notion of a potential role of metabotropic glutamate receptors (mGluRs) in learning and memory formation, but the specific function of the different classes or individual subtypes remains elusive. Furthermore, our knowledge with respect to different learning mechanisms is still fragmentary. In an attempt to clarify further the function of mGluRs in learning, rats were trained in various paradigms in the presence/absence of the specific class I antagonist 1-aminoindan-1,5-dicarboxylic acid (AIDA). Intraperitoneal application of AIDA prior to training led to enhanced within-session performance in animals trained in a positively reinforced reference memory task in a three-choice maze. However, this enhancement did not result in increased retention as measured by the number of correct responses during the first four trials of each session on subsequent days. The increase was purely an enhancement in within-session performance, required doses higher than 2 mg/kg, and was not accompanied by an unspecific increase in activity as monitored in the open field. By contrast, AIDA animals trained in a combined shock-reinforced contextual and cue conditioning paradigm demonstrated a pronounced retention deficit compared with controls in conditioning to the context, but not the cue (a high-frequency tone). Although within-session performance during context and cue periods was slightly increased in the AIDA group, the difference did not reach significance. Drug-induced hyperactivity, which could account for the memory deficit, was excluded by recordings of activity in specific activity cages. These results shed new light on the possible function of class I mGluRs in learning and memory formation and imply that systemic blockade of class I mGluRs may enhance short-term memory under certain learning conditions.

Animals↗

Transient translocation of protein kinase Cgamma in hippocampal long-term potentiation depends on activation of metabotropic glutamate receptors.

Protein kinase C has been implicated in long-term regulation of cellular functions including induction and maintenance of hippocampal long-term potentiation. In the present study the time-course of long-term potentiation-induced translocation of Ca(2+)-dependent protein kinase C isoenzymes (PKCalpha/beta and PKCgamma) was investigated. Quantitative immunoblot analysis was used to measure translocation of these isoenzymes between cytosolic, membrane-associated and membrane-inserted fraction at 5, 15 and 60 min after induction of long-term potentiation in the dentate gyrus in vivo. To investigate the involvement of metabotropic glutamate receptors in protein kinase C regulation during long-term potentiation induction, additional animals were treated before tetanization with (R,S)-alpha-methyl-4-carboxyphenylglycine, an antagonist of metabotropic glutamate receptors. Brief tetanic stimulation of the perforant path resulted in a 100-150% increase in the population spike amplitude in response to test stimuli 5, 15 or 60 min after stimulation in both untreated and (R,S)-alpha-methyl-4-carboxyphenylglycine-treated animals. Only those rats showing clear potentiation were selected for further biochemical analysis of the potentiated dentate gyrus. Five minutes after high-frequency stimulation the subcellular distribution of all studied protein kinase C isoenzymes was unchanged compared with controls. PKC-gamma translocated into the cytosol 15 min after tetanization and this redistribution was blocked by (R,S)-alpha-methyl-4-carboxyphenylgly-cine pretreatment. By contrast, PKC alpha/beta levels increased in the cytosolic fraction only 60 min after tetanization, but in a (R,S)-alpha-methyl-4-carboxyphenylglycine-independent manner. In an additional set of experiments it was shown that (R,S)-alpha-methyl-4-carboxyphenylglycine alone applied intraventricularly had no effect on the subcellular distribution of the studied isoenzymes. The data suggest that PKCalpha/beta and PKCgamma are activated during different post-tetanic phases and metabotropic glutamate receptor activation might be essential for tetanus-induced translocation of postsynaptic PKCgamma only.

Animals↗

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↗

Nucleus accumbens lesions impair context, but not cue, conditioning in rats.

Previous work has provided evidence of a role for the hippocampal formation in contextual as opposed to cue conditioning. Similar deficits have been observed after transection of the fimbria/fornix, part of which consists of the hippocampal-nucleus accumbens (N.Acc) connection arising from both the dorsal and ventral subiculum. By means of electrolytic lesions of the N.Acc, we showed that the subiculo-accumbens projection appears to participate in aversive conditioning to context, but not to a cue (tone). Freezing, measured as an index of learning, in the experimental context was greatly reduced in animals with lesions of the N.Acc, as compared with sham-operated controls. No difference was found in freezing to a distinct tone. These data lend further support to the notion that the N.Acc is an important interface between limbic structures and motor output.

Acoustic Stimulation↗

Class I mGlu receptor antagonist 1-aminoindan-1,5-dicarboxylic acid blocks contextual but not cue conditioning in rats.

It is widely believed that metabotropic glutamate (mGlu) receptors play a potential role in memory formation. However, the particular function of different classes of mGluRs, or even subtypes, remains elusive. We show here that intraperitoneal injection of the class I selective antagonist 1-aminoindan-1,5-dicarboxylic acid (AIDA) in concentrations of 0.18 or 1.8 mg/kg 25 min prior to acquisition training blocks hippocampus-dependent contextual, but not hippocampus-independent cue, conditioning in rats. These data provide the first evidence for a specific role of mGlu receptors, class I in particular, in hippocampus-dependent learning tasks.

Acoustic Stimulation↗