Biomedical subjects

F Bermúdez-Rattoni

Publications and source records attributed to F Bermúdez-Rattoni.

At least 19 recordsLinked to original sources

PubMed2002

Differential effects of bicuculline and muscimol microinjections into the nucleus basalis magnocellularis in taste and place aversive memory formation.

The role of the nucleus basalis magnocellularis (NBM) in learning and memory has been demonstrated in different learning paradigms such as conditioned taste aversion (CTA) and inhibitory avoidance (IA). This participation has been related to the cholinergic system, but recent studies have reported the potential role of other neurotransmitters such as GABA. The effects of acute intracerebral administration of the GABAergic antagonist bicuculline (0.05 microg) and the GABAergic agonist muscimol (0.05 microg) into the NBM of male Wistar rats were assessed in CTA and IA learning. In both learning tasks, the drug administration was performed before the acquisition. Taste aversion learning was not affected by the infusion of any of the drugs administered. IA acquisition was not affected by the administration of bicuculline or muscimol, requiring similar number of trials to reach the learning criterion. However, when the rats were tested 24 h later, those injected with bicuculline or muscimol showed an impairment of the IA learning. The present results support a role of the GABAergic system in the consolidation process of IA learning.

Animals↗

PubMed2002

Differential involvement of cortical muscarinic and NMDA receptors in short- and long-term taste aversion memory.

In conditioned taste aversion, an animal avoids a taste previously associated with toxic effects, and this aversive memory formation requires an intact insular cortex. In this paper, we investigated the possible differential involvement of cholinergic and glutamatergic receptors in the insular cortex in short-term memory (STM) and long-term memory (LTM) of taste aversion in rats. Taste aversion was induced by intraperitoneal administration of lithium chloride (a malaise-inducing drug) 15 min after experience with an unfamiliar taste. In order to test STM and LTM of taste aversion, taste stimulus was again presented 4 h and 72 h after lithium injection, respectively. During the acquisition, microinjection of the muscarinic antagonist, scopolamine, in the insular cortex before, but not after, the presentation of the new taste, abolished STM as well as LTM. Blockade of the NMDA receptor, in the insular cortex, by AP5 before, but not after, the presentation of the taste stimulus, impaired LTM but left STM intact. Moreover, when injected 1 h after malaise induction (i.e., during taste-illness association), AP5 disrupted both STM and LTM. These results suggest that activation of muscarinic receptors in the insular cortex is involved in the acquisition of taste memory, whereas NMDA receptors participate in taste memory consolidation. These data demonstrate that different neurochemical mechanisms subserve different memory phases. NMDA receptors are also probably involved in processing the visceral input, thus allowing subsequent taste-illness association. This indicates that in the same cortical area the same neurotransmitter system can be involved in distinct processes: taste memory consolidation vs. taste-illness association.

2-Amino-5-phosphonovalerate↗

PubMed2001

Spatial long-term memory is related to mossy fiber synaptogenesis.

Structural synaptic changes have been suggested to underlie long-term memory formation. In this work, we investigate if hippocampal mossy fiber synaptogenesis induced by water maze overtraining can be related with long-term spatial memory performance. Rats were trained in a Morris water maze for one to five identical daily sessions and tested for memory retrieval 1 week and 1 month after training. After the last test session, the rat brains were obtained and processed for Timm's staining to analyze mossy fiber projection. The behavioral results showed that with more training, animals showed a better performance in the memory tests, and this performance positively correlates with Timm's staining in the stratum oriens. Furthermore, with the use of the NMDA antagonist MK801 before, but not after acquisition, water maze spatial memory was impaired. Increased Timm's staining in the stratum oriens was observed in the animals treated with MK801 after acquisition but not in those treated before. Finally, we observed that mossy fiber synaptogenesis occurs mainly in the septal region of the dorsal hippocampus, supporting the idea that this anterior region is important for spatial memory. Altogether, these results suggest that mossy fiber synaptogenesis can be related with spatial long-term memory formation.

Animals↗

PubMed2000

Differential participation of the NBM in the acquisition and retrieval of conditioned taste aversion and Morris water maze.

Deficits in both learning and memory after lesions of the cholinergic basal forebrain, in particular the nucleus basalis magnocellularis (NBM), have been widely reported. However, the participation of the cholinergic system in either acquisition or retrieval of memory process is still unclear. In this study, we tested the possibility that excitotoxic lesions of the NBM affect either acquisition or retrieval of two tasks. In the first experiment, animals were trained for two conditioned taste aversion tasks using different flavors, saccharine and saline. The acquisition of the first task was before NBM lesions (to test retrieval) and the acquisition of the second task was after the lesions (to test acquisition). Accordingly, in the first part of the second experiment, animals were trained in the Morris water maze (MWM), lesioned and finally tested. In the final part of this experiment, another set of animals was lesioned, then trained in the MWM and finally tested. All animals were able to retrieve conditioned taste aversion (CTA) and MWM when learned before NBM lesions; however, lesions disrupted the acquisition of CTA and MWM. The results suggest that the NBM and cholinergic system may play an important role in acquisition but not during retrieval of aversive memories.

Acetylcholinesterase↗

PubMed2000

Cortical cholinergic activity is related to the novelty of the stimulus.

A number of studies have related cholinergic activity to the mediation of learning and memory. However, the acetylcholine (ACh) participation has been recently implicated in the early stages of memory formation but not during retrieval. The aim of the present study is to evaluate ACh release in the insular cortex (IC) during presentation of different taste stimuli and during their re-exposition by means of the free-moving microdialysis technique. We evaluated the changes in ACh release when a novel taste, saccharin or quinine was presented to the rat and after several presentations of saccharin. Unilateral microdialysis was performed in the IC 1 h before and 1 h after the presentation of: (1) a familiar stimulus (water), (2) a novel taste (quinine), (3) another novel taste (saccharin), (4) a second presentation, (5) a third presentation, and (6) a fourth presentation of saccharin. The volume consumed by the animals was registered as a behavioral parameter. The ACh levels from the microdialysis fractions were analyzed by an HPLC-ED system. Biochemical results showed a significant increment in the cortical ACh release induced by a novel stimulus compared with the release observed during the presentation of a familiar stimulus. The ACh release observed after several presentations of the stimuli decreased to the same levels as those produced by the familiar taste, indicating an inverse relationship between familiarity and cortical ACh release. These results suggest that the cholinergic system plays an important role in the identification and characterization of different kinds of stimuli.

Acetylcholine↗

PubMed2000

Long-term potentiation in the insular cortex enhances conditioned taste aversion retention.

Long-lasting changes in synaptic strength, such as long-term potentiation (LTP), are thought to underlie memory formation. Recent studies on the insular cortex (IC), a region of the temporal cortex implicated in the acquisition and retention of conditioned taste aversion (CTA), have demonstrated that tetanic stimulation of the basolateral nucleus of the amygdala (Bla) induce LTP in the IC of adult rats in vivo, as well as, that blockade of N-methyl-D-aspartate (NMDA) receptors disrupts CTA and IC-LTP induction in vivo. Here, we present experimental data showing that induction of LTP in the Bla-IC projection previous to CTA training enhances the retention of this task. These findings are of particular interest since they provide support for the view that the neural mechanisms underlying neocortical LTP may contribute to memory related functions performed by the IC.

Amygdala↗

PubMed1999

Redundant basal forebrain modulation in taste aversion memory formation.

Mnemonic deficits resulting from excitotoxic lesion of the basal forebrain have been classically attributed to the resulting depletion of cortical acetylcholine activity. It has been demonstrated that in spite of the strong cholinergic depletion after injections into the basal forebrain of the immunotoxin 192IgG-saporin, no detectable deficit can be found in the acquisition of several learning tasks, including conditioned taste aversion. Conversely, NMDA-induced lesions of the basal forebrain strongly impair taste aversion learning. In this study we show that 192IgG-saporin produces an efficient and selective cholinergic deafferentation of the rat neocortex but not the amygdala. Furthermore, a stronger relationship between severity of memory impairment after NMDA lesions and basoamygdaloid cholinergic deafferentation was found. Therefore, in a second experiment, we show that combining NMDA-induced lesions into the basolateral amygdala with 192IgG-saporin injections into the basal forebrain results in a strong disruption of taste aversion learning, whereas none of these treatments were by themselves capable of producing any detectable impairment in this learning task. The double lesion effect was only paralleled by simple NMDA lesions into the basal forebrain, suggesting that the learning deficits associated to excitotoxic lesions of the basal forebrain are the result of the simultaneous destruction of the corticopetal and basoamygdaloid interaction. A model is proposed, according to which the modulation of learning processes exerted by the basal forebrain can be redundantly performed by both the basocortical and basoamygdaloid pathway.

Acetylcholinesterase↗

PubMed1999

Differential effects of 192IgG-saporin and NMDA-induced lesions into the basal forebrain on cholinergic activity and taste aversion memory formation.

Mnemonic deficits resulting from excitotoxic lesion of the basal forebrain have been classically attributed to the resulting depletion of cortical acetylcholine activity. In this study, we have performed a detailed analysis of the cholinergic status of the insular cortex (IC) following local injections of either 192IgG-saporin (192IgG-sap) or N-methyl-D-aspartate (NMDA) directly into the nucleus basalis magnocellularis (NBM). By means of in vivo microdialysis, we show that the immunotoxin lesion results in an almost complete lack of extracellular acetylcholine release, whereas NMDA-induced lesions result in a marginal reduction in cortical cholinergic activity. Choline-acetyltransferase activity in the IC further confirmed this differential pattern of cortical deafferentation. Surprisingly, however, only NMDA-induced lesions showed a strong disruptive effect upon taste aversion learning whereas no detectable deficits could be found following 192IgG-sap lesions. By combining intrabasal injections of 192IgG-sap with acute pre-training infusions of the cholinergic antagonist scopolamine into the IC, a strong disruption of taste aversion was attained. These results imply that residual cholinergic activity, following 192IgG-saporin lesions, might be still critical for normal cortical mediation of memory processing. They also support the role of basal forebrain in mediating learning and memory processes, and demonstrate that mnemonic deficits resulting from excitotoxic lesions of the basal forebrain are not the sole result of cortical acetylcholine activity hypofunction.

Acetylcholine↗

PubMed1999

Reversible inactivation of the nucleus basalis magnocellularis induces disruption of cortical acetylcholine release and acquisition, but not retrieval, of aversive memories.

The basal forebrain complex, which includes the nucleus basalis magnocellularis (NBM), provides widespread cholinergic and gamma-aminobutyric acid-containing projections throughout the brain, including the insular and pyriform cortices. A number of studies have implicated the cholinergic neurons in the mediation of learning and memory processes. However, the role of basal forebrain activity in information retrieval mechanisms is less known. The aim of the present study is to evaluate the effects of reversible inactivation of the NBM by tetrodotoxin (TTX, a voltage-sensitive sodium channel blocker) during the acquisition and retrieval of conditioned taste aversion (CTA) and to measure acetylcholine (ACh) release during TTX inactivation in the insular cortex, by means of the microdialysis technique in free-moving rats. Bilateral infusion of TTX in the NBM was performed 30 min before the presentation of gustative stimuli, in either the CTA acquisition trial or retrieval trial. At the same time, levels of extracellular ACh release were measured in the insular cortex. The behavioral results showed significant impairment in CTA acquisition when the TTX was infused in the NBM, whereas retrieval was not affected when the treatment was given during the test trial. Biochemical results showed that TTX infusion into the NBM produced a marked decrease in cortical ACh release as compared with the controls during consumption of saccharin in the acquisition trial. Depleted ACh levels were found during the test trial in all groups except in the group that received TTX during acquisition. These results suggest a cholinergic-dependent process during acquisition, but not during memory retrieval, and that NBM-mediated cholinergic cortical release may play an important role in early stages of learning, but not during recall of aversive memories.

Acetylcholine↗

PubMed1999

Synaptogenesis of mossy fibers induced by spatial water maze overtraining.

Synaptic plasticity has been proposed as a mechanism underlying learning and memory. Synaptic reorganization of hippocampal mossy fibers has been observed after experimentally induced epilepsy, and after brief high-frequency activation inducing long-term potentiation. Furthermore, it has been suggested that synaptic changes in the hippocampus may occur after spatial learning. In this study, by using a zinc-detecting histologic technique (Timm), we demonstrate a significant increase of mossy fiber terminals in the CA3 stratum oriens region induced by training rats during 3 days in a spatial Morris water maze. In contrast, animals trained for only 1 day and animals that were just allowed to swim or were overtrained in a stress-motivated inhibitory avoidance task did not show increments of mossy fiber terminals in the stratum oriens. Electron microscopy confirmed that synaptic density of mossy fiber terminals in the stratum oriens increases significantly in water maze overtrained animals compared with the swimming control animals. Taken together, these results suggest that overtraining in a spatial learning task induces mossy fiber synaptogenesis that could be involved in the mechanisms underlying long-term memory storage. Hippocampus 1999;9:631-636.

Analysis of Variance↗

PubMed1999

Conditioned enhancement of antibody production is disrupted by insular cortex and amygdala but not hippocampal lesions.

Pavlovian conditioning procedures can be used to activate the immune system. A reliable conditioned increase of antibody production can be obtained in rats that have previously received a gustative or odor stimulus as the conditioned stimulus paired with an antigen, by exposing the animals to the conditioned stimulus alone. We showed evidence that an excitotoxic lesion bilaterally applied into the insular cortex or the amygdala, but not into the dorsal hippocampus, impaired the acquisition of both odor and gustatory conditioned immune enhancement. We found no effects of lesions on normal antibody production. These results suggest that the amygdala and the insular cortex are involved in the neural-immune interactions that mediate conditioned immunity.

Amygdala↗

PubMed1999

Blockade of N-methyl-D-aspartate receptors in the insular cortex disrupts taste aversion and spatial memory formation.

The present experiments examined the effects of direct intracortical microinjections of the N-methyl-D-aspartate receptor antagonist 2-amino-5-phosphonovaleric acid directly into the insular cortex of rats, before or immediately after training of conditioned taste aversion and the water maze spatial learning task. In the first series of experiments animals received bilateral injections of 2-amino-5-phosphonovaleric acid prior to taste aversion conditioning or spatial training. A strong disruptive effect was found in the acquisition of training tasks. To determine the possible involvement of N-methyl-D-aspartate receptors in the early post-training processes taking place in the cortex during both learning paradigms, in a second series of experiments, animals received bilateral 2-amino-5-phosphonovaleric acid microinjections 30, 60 or 120 min after the acquisition trial, and 15 min before the retention test. For spatial learning successive treatments were independently done either starting at the onset of the asymptotic phase of the learning curve, 0, 30 or 120 min after finishing the training session, as well as 15 min before the retention test trial. The conditioned taste aversion task remained sensitive to N-methyl-D-aspartate blockade during a period of at least 2 h after the first presentation of the gustatory stimulus, while in the case of the spatial learning task, a gradually decreasing effect was observed from the onset of the asymptotic phase onwards. Taken together, these results provide direct evidence for N-methyl-D-aspartate receptor involvement in cortical regulation of memory formation. Furthermore, our results suggest that in the same cortical region, a different time-course for the activation of N-methyl-D-aspartate-dependent mechanisms occurs during the early formation of cortically mediated memories, depending on the particular behavioural task.

2-Amino-5-phosphonovalerate↗

PubMed1998

In vivo long-term potentiation in the insular cortex: NMDA receptor dependence.

It has been demonstrated that the insular cortex (IC) plays an important role in the acquisition and storage of different aversive motivated learning tasks like conditioned taste aversion, spatial maze and inhibitory avoidance. It is of particular interest to investigate whether activity-dependent modification of synaptic efficacy, a presumptive mechanism for learning and memory, is present in this cortical region. Here, we address this issue by examining the induction of synaptic plasticity, long-term potentiation (LTP) in in vivo preparations. The results showed that high frequency stimulation of the basolateral amygdaloid nucleus (Bla) induced LTP in the IC. The LTP induced by tetanus was blocked by application of the N-methyl-D-aspartate (NMDA) receptor antagonists CPP and MK-801, indicating that NMDA receptors were responsible for its induction. These results suggest that in vivo tetanus induced LTP of the Bla-IC projection is a possible mechanism for the memory-related functions performed by the IC.

Amygdala↗

PubMed1998

Differential effects of NMDA-induced lesions into the insular cortex and amygdala on the acquisition and evocation of conditioned immunosuppression.

It has been established that the insular cortex (IC) mediates conditioned taste aversion, and recently we have demonstrated that lesions of this structure disrupt the acquisition of conditioned immunosuppression (CIS). The IC is functionally and reciprocally interconnected with the amygdala (AM) which has been suggested to be involved in neural-immune interactions. The aim of this work was to test the effects of NMDA-induced lesions in either the IC or AM in the acquisition (lesions made before conditioning) and evocation (lesions made after conditioning) of a conditioned immunosuppression task, obtained by one single pairing of saccharin taste and the immunosuppressive drug, cyclophosphamide. AM and IC lesioned rats were separated into four groups: the first two received lesions before and the other two were lesioned after the acquisition of conditioned immunosuppression. Twenty days after conditioning, animals were reexposed to saccharin and immunized with ovalbumin. After immunization, blood samples were taken, and analyzed by ELISA. The results showed that IC lesions disrupted the acquisition and evocation of CTA and CIS. Conversely, AM lesions disrupted only the acquisition of CIS. These data suggest that the IC is involved in the neural mechanisms underlying the acquisition and evocation of conditioned immunosuppression, and the amygdala could be important in mediating the input of the immune information necessary for the acquisition of conditioned immunosuppression.

Amygdala↗

PubMed1998

Acetylcholine determination of microdialysates of fetal neocortex grafts that induce recovery of learning.

The microdialysis technique for acetylcholine (ACh) first became possible when sensitive and specific assays for ACh (pmol/sample range) were developed [G. Damsma, B.H.C. Westerink, P. de Boer, J.B. de Vries, A.S. Horn, Determination of basal acetylcholine release in freely moving rats by transstriatal dialysis coupled to on-line HPLC analysis: pharmacological aspects, Life Sci. 43 (1988) 1161-1168; G. Damsma, B.H.C. Westerink, A. Imperato, H. Rollema, J.B. de Vries, A. S. Horn, Automated brain dialysis of acetylcholine in freely moving rats: detection of basal acetylcholine, Life Sci. 41 (1987) 873-876; P.E. Potter, J.L. Meek, N.H. Neff, Acetylcholine and choline in neural tissue measured by HPLC with electrochemical detection, J. Neurochem. 41 (1983) 188-194; B.H.C. Westerink, G. Damsma, Determination of acetylcholine in microdialysates by HPLC and electrochemical detection, Neurosci. Protocols 20 (1993) 1-9.]. In the present protocol, the microdialysis technique was used to correlate ACh release with the recovery of the ability to acquire a conditioning taste aversion (CTA), by fetal brain grafts in insular cortex (IC) lesioned rats [M.I. Miranda, A.M. Lopez-Colome, F. Bermúdez Rattoni, Recovery of conditional taste aversion induced by fetal neocortex grafts. In vivo correlation of acetylcholine levels, Brain Res. 759 (1997) 141-148]. Three groups of IC lesioned rats showing disrupted CTA received cell suspension grafts of fetal tissue dissected from either the IC or occipital cortex (OC) of 16-day-old rat fetuses. One of the groups of IC-grafted animals was tested after 15 days post-graft; the other groups, IC- and OC-grafted animals, were tested after a recovery time of 45 days, as well as the groups of lesioned and unoperated animals used as control. After the CTA test, guide cannulas were stereotaxically implanted into the IC of all groups. Two days later, microdialysis was performed to determine the extracellular levels of ACh inside the graft. The dialysates were analyzed by high-performance liquid chromatography and electrochemical detection. The ACh was converted by the enzyme acetylcholinesterase to choline, and subsequently by choline oxidase to hydrogen peroxide [J.L. Meek, C. Eva, Enzymes adsorbed on an ion exchanger as a post-column reactor: application to acetylcholine measurement, J. Chromatogr. 317 (1984) 343-347.]. The reactor with these enzymes was placed between the analytical column and the electrochemical detector. The hydrogen peroxide produced was detected with a platinum electrode, and choline was determined concurrently. We believe that the application of free-moving microdialysis as a method to measure the cholinergic levels inside the transplant at two post-graft periods, is a good, direct technique to correlate the effects of ACh levels from the fetal grafts in lesioned rats.

Acetylcholine↗

PubMed1998

Long-term memory retrieval deficits of learned taste aversions are ameliorated by cortical fetal brain implants.

In this study, the effects that fetal brain implants have on the ability to retrieve the memory for a previously acquired conditioned taste aversion (CTA) in insular cortex (IC) lesioned rats were tested. Several groups of rats were trained for a CTA, were lesioned in the IC 4 days later, were implanted with different fetal cortical tissues, were treated or untreated with nerve growth factor (NGF), and then were tested for recall either 15 or 45 days later. Rats were then retrained and tested with a different taste and in the inhibitory avoidance (IA) task. All implanted animals recovered the retrieval of CTAs learned before IC lesions; however, only the homotopic IC implants at 45 days or NGF supplemented at 15 days induced recovery of the ability to learn CTA. The latter effect was also true for IA learning. The results suggest that the brain mechanisms for recovery of memory functions are different from those of learning abilities.

Animals↗

PubMed1997

Recovery of taste aversion learning induced by fetal neocortex grafts: correlation with in vivo extracellular acetylcholine.

Rats showing disrupted taste aversion due to insular cortex lesions, received either homotopic or heterotopic (occipital) cortical fetal brain grafts. Behavioral results showed that the recovery of the ability to acquire conditioned taste aversions induced by fetal grafts depended on post-graft time (45 but not at 15 days) and tissue specificity (homotopic but not heterotopic). In vivo analysis of acetylcholine (ACh) release revealed that only the group receiving homotopic grafts and tested 45 days post graft had a release of ACh after KCl stimulation similar to that in the control group. Furthermore, homotopic grafts and lesioned groups showed significantly weaker specific receptor binding of [3H]L-glutamate compared with controls. These results suggest that ACh is specifically involved in the process of behavioral recovery induced by homotopic cortical transplants.

Acetylcholine↗

PubMed1997

Learning impairment and cholinergic deafferentation after cortical nerve growth factor deprivation.

Cholinergic basal forebrain (CBF ) neurons have been shown to respond in vivo to exogenous administration of NGF. Although neurotrophins and their receptors are widely expressed in the CNS, little data exist for the physiological significance of endogenous neurotrophin signaling in CNS neurons. To test directly whether cortically derived NGF is functionally required for the cholinergic functions mediated by the cerebral cortex, repeated injections of anti-NGF mAbs were locally applied into the insular cortex (IC) of rats. The biochemical results, using an in vivo microdialysis technique, showed a dramatic lack of extracellular release of acetylcholine after high potassium stimulation compared with controls. Furthermore, by using small injections of the neurotracer fluorogold, we found a corresponding disruption in the connectivity between the IC and the CBF. Behavioral experiments showed that the NGF antibodies applied into the IC produced a significant disruption on the acquisition of conditioned taste aversion and inhibitory avoidance learning. However, the same animals were able to recall the taste aversion when the conditioning trial was established before injections of NGF antibodies. Given these results, it seems that cortical cholinergic functions are actively dependent on locally derived NGF in the adult normal brain, and that the cholinergic activity from the CBF is not necessary for recalling aversive stimuli, but is necessary for the acquisition of aversively motivated conditionings.

Age Factors↗