Biomedical subjects

F Bermúdez-Rattoni

Publications and source records attributed to F Bermúdez-Rattoni.

At least 37 records · Page 2Linked to original sources

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↗

PubMed1997

Insular cortex and amygdala lesions induced after aversive training impair retention: effects of degree of training.

These experiments examined the effects of N-methyl-D-aspartate (NMDA)-induced lesions of the amygdala and insular cortex induced 1 week after rats were trained on a footshock motivated escape task in a two-compartment runway. In the first experiment, male rats were given 10 training trials and, 1 week later, received microinjections of a buffer solution or NMDA into either the insular cortex (IC) or the amygdala (AM). In an inhibitory avoidance retention test 1 week after the microinjections, the retention latencies (i.e., latencies to enter the compartment where shock had been delivered) of both the AM- and "IC-lesioned" groups were significantly lower than those of the buffer-injected groups. Additionally, in comparison with the buffer controls, rats in the two lesioned groups made significantly more crossings between the two compartments during the retention test. In a second experiment, male rats were given 1, 10, or 20 escape training trials 1 week before receiving either sham or NMDA lesions in the IC. The retention test was given 1 week after microinjection. Those sham or lesioned animals that were given only one training trial did not demonstrate retention. Both lesioned groups given 10 or 20 training trials were significantly disrupted on both the step-through latencies, and the number of crossings between the two compartments. The retention-impairing effects of NMDA-induced lesions were slightly attenuated in the group given 20 escape training trials. The findings provide additional evidence that the AM and the IC are involved in regulating the long-term retention of aversively motivated training.

Amygdala↗

PubMed1996

Insular cortex lesions impair the acquisition of conditioned immunosuppression.

Conditioned immunosuppression can be readily obtained in animals by associating a taste with an immunosuppressive drug. On subsequent exposure to the conditioned taste, the animals show an attenuated immune response and also exhibit a conditioned taste aversion. It has been established that insular cortex lesions disrupt the acquisition of conditioned taste aversion. The effect of NMDA-induced lesions in either the insular cortex or the parietal cortex of male Wistar rats was evaluated in the acquisition of conditioned immunosuppression in two experiments. Unlesioned control rats showed the conditioned immunosuppressive response after reexposure to the taste, as indicated by lower hemagglutinating titers to sheep red blood cells in the first experiment and by a decreased IgM production to ovalbumin, measured by ELISA, in the second experiment. Insular cortex-lesioned rats did not show the conditioned immunosuppression in either experiment, while parietal cortex lesions and the sham-lesioned animals presented a clear decrease of hemagglutinating titer and a low IgM production. The insular cortex lesions did not affect the normal immune response, showing normal hemagglutinating titers and IgM production when compared to nonconditioned controls. The immunosuppressive action of cyclophosphamide also remained unaltered. In conclusion, these results show that the insular cortex is essential for the acquisition of conditioned immunosuppression.

Animals↗

PubMed1996

Differential effects of anterior and posterior insular cortex lesions on the acquisition of conditioned taste aversion and spatial learning.

In this study, we evaluated the effects of NMDA-induced lesions in different sites of the insular cortex of the rat on the acquisition of conditioned taste aversion and spatial learning in the Morris water maze. The lesions were produced by bilateral microinjections of NMDA in the insular cortex at +3.7 mm (Anterior group), +1.7 mm (Central group), and -0.3 mm (Posterior group) anteroposterior from bregma. The results showed that the central and posterior, but not the anterior, lesions disrupted the acquisition of water maze learning as measured by the high latency to reach the target. In contrast, the conditioned taste aversion learning was disrupted by lesions in the central but not in the anterior or posterior insular cortex. These data confirm functional heterogeneity of the insular cortex and demonstrate that the more caudal parts are only necessary for acquisition of the water maze task, while the central insular cortex is crucial for the acquisition of both the conditioned taste aversion learning and the Morris water maze.

Animals↗

PubMed1995

Enhancement of antibody production by a learning paradigm.

The experiments described here show that production of serum antibody to a defined protein antigen (hen egg-white lysozyme) can be elicited by classical Pavlovian conditioning in Wistar rats. Reexposure of animals to a gustatory conditioned stimulus that had previously been paired with antigen induces a reliable increase in antibody production. This conditioned production of antibodies of IgM and IgG isotypes is similar to that found in secondary responses elicited by reinjection of antigen. These findings demonstrate that the immune system can be stimulated to produce apparently normal antibody responses by a simple behavioral paradigm.

Animals↗

PubMed1994

Accelerating behavioral recovery after cortical lesions. I. Homotopic implants plus NGF.

We recently demonstrated that fetal brain implants produced a significant recovery in the ability of insular cortex (IC)-lesioned rats to learn a conditioned taste aversion (CTA). We now report effects on the recovery of CTA and of a second measure of learning, inhibitory avoidance (IA), of supplementing the implants with nerve growth factor (NGF). Four groups of male Sprague-Dawley animals showing disrupted taste aversion following IC lesions, plus two control groups, received different experimental treatments: Group 1, unlesioned control; Group 2, homotopic IC implants without NGF; Groups 3 and 4, IC implants + NGF; Group 5, heterotopic occipital cortical implants + NGF; and Group 6, without an implant as a lesioned control. All groups except Group 4 were trained pre- and postimplant in the CTA paradigm. Two days after CTA testing postimplant, all groups received IA training. Behavioral results showed that insular cortex implants with NGF promoted recovery to control levels of the ability to learn both tasks at 15 days postimplant. Those animals that received occipital implants with NGF or insular cortex with vehicle or remained without implants did not show any significant behavioral recovery at 15 days postimplant. These findings suggest that NGF associated with homotopic implants facilitates recovery of learning abilities in insular cortex-lesioned rats and suggest that similar treatments with NTFs may have analogous effects when lesions involve other brain areas.

Animals↗

PubMed1994

Accelerating behavioral recovery after cortical lesions. II. In vivo evidence for cholinergic involvement.

We recently demonstrated that insular cortex (IC) fetal implants supplemented by nerve growth factor (NGF) can accelerate the recovery of behavioral deficits induced by IC brain lesions. In the present report we describe results on in vivo assays of acetylcholine (ACh) turnover in the IC of rats subjected to the same brain lesion and implant treatments used in that research and for which detailed behavioral data are available. The neurochemical assays were carried out immediately after completion of the behavioral measurements. The assays showed that implants or NGF with heterotopic tissue continued to be associated with elevated levels of ACh and with deficits in learning and memory at a time postlesion when both behavior and ACh turnover in vivo, after treatment with homotopic implants and NGF combined, were at nonlesioned control levels. The results support the concept that, in vivo, the cholinergic neurotransmitter system is intimately involved in recovery from IC lesion-induced deficits in behavior and show that a combination of homotopic implant and NGF may be used as a means of manipulating that system to accelerate the repair of such deficits. Mechanisms by which this combination produces its effects are considered and the possibility is suggested that other neurotrophic factors (NTF) may also be useful when other types of brain lesions are involved.

Acetylcholine↗

PubMed1994

Differential recovery of inhibitory avoidance learning by striatal, cortical, and mesencephalic fetal grafts.

Four groups of male Wistar rats showing disrupted inhibitory avoidance conditioning due to striatal lesions were studied. Three groups received striatal, cortical, or ventral mesencephalic brain grafts and the fourth group remained as a lesioned control. Sixty days postgraft the animals were retrained in an inhibitory avoidance task. The striatal-grafted animals were the only group that significantly improved in the ability to acquire the inhibitory avoidance task. Acetylcholinesterase histochemistry revealed positive patches of cells in the striatal grafts. Cortical grafts showed less reactivity, without patches. Immunocytochemical analyses for tyrosine hydroxylase revealed positive cell reactivity in the mesencephalic grafts and few positive fibers were detected in the border between the striatal grafts and the host tissue. These results demonstrate that striatal but not cortical or mesencephalic brain grafts can promote the restoration of the ability to acquire an inhibitory avoidance task and suggest that the acetylcholine tissue content is involved in the behavioral recovery.

Acetylcholine↗

PubMed1993

Hypothalamic but not cortical grafts induce recovery of sexual behavior and connectivity in medial preoptic area-lesioned rats.

We have previously shown that hypothalamic fetal brain grafts induced recovery of sexual behavior in medial preoptic area (MPOA)-lesioned male rats. In the present series of experiments, male rats with completely abolished sexual behavior by MPOA lesions received either hypothalamic or frontal cortical fetal grafts. The animals that received hypothalamic grafts showed a gradual recovery of sexual behavior. In contrast, those animals who received cortical grafts did not recover sexual behavior during the 15 weeks after the graft. In addition, to evaluate the connectivity of the grafted tissue with the host brain, a retrograde tracer, fluorogold, was injected in the dorsal tegmental area. Fluorogold-labeled cells were found in the hypothalamic, but not in the cortical grafts. These results suggest that specificity of the grafted tissue and connectivity between brain grafts and host tissue are necessary for the recovery of male sexual behavior in MPOA-lesioned rats.

Animals↗

PubMed1993

Effects of excitotoxic lesions of the nucleus basalis magnocellularis on conditioned taste aversion and inhibitory avoidance in the rat.

The role of the nucleus basalis magnocellularis (NBM) in a variety of learning tasks is well known. Lesions of this nucleus result in a reduction of cholinergic transmission throughout a vast portion of the cortex. Because cholinergic transmission in the insular cortex seems to be important for the acquisition of conditioned taste aversion, the aim of the present work was to study the effects of bilateral chemically induced lesions of the NBM on this conditioning, as correlated with some cholinergic markers in the insular cortex. The effect on inhibitory avoidance was also studied. Lesions prevented the acquisition of the aversion and disrupted retention of the task in previously trained animals. Learning in the inhibitory avoidance paradigm was also notably affected. Postlesion reductions of choline acetyltransferase and acetylcholinesterase activities and of K(+)-stimulated [3H]acetylcholine release were found in the insular cortex. Further, in intact rats labeling of NBM neurons was observed by retrograde tracing after injection of Fluoro-Gold into the insular cortex. These findings indicate that the NBM is involved in the neural integration of feeding behavior and that its cholinergic projection to the insular cortex is one of the implicated neurotransmitter systems.

Acetylcholinesterase↗

PubMed1993

Effects of catecholaminergic depletion of the amygdala and insular cortex on the potentiation of odor by taste aversions.

This experiment examined the effects of catecholamine depletion of the amygdala or insular cortex on the acquisition of olfactory and gustatory learning tasks. Bilateral lesions with 6-hydroxydopamine (4 micrograms/0.5 microliters) were done in either amygdala or insular cortex of Wistar male rats, with two groups receiving sham lesions. All four groups of animals were trained and tested in the potentiation of odor by taste aversion paradigm. The results showed that the amygdala-lesioned group acquired the taste, but not hte odor aversion, while the insular cortex-lesioned group acquired odor, but not taste aversion. Both sham groups showed strong taste and odor aversions. Catecholamine levels in both lesioned groups were significantly lower than those in the sham groups. These results suggest that catecholamines are necessary in the insular cortex for the acquisition of taste and in the amygdala for the acquisition of odor aversion in the potentiation of odor by taste aversion paradigm.

Amygdala↗

PubMed1991

Time-dependent recovery of taste aversion learning by fetal brain transplants in gustatory neocortex-lesioned rats.

We recently showed that fetal brain transplants produced a significant recovery in the ability of gustatory neocortex-lesioned rats to learn a conditioned taste aversion. In this report we assessed the capability of gustatory neocortex fetal brain transplants to produce behavioral recovery at different times. Four groups of male Wistar rats showing disrupted taste aversions due to gustatory neocortex lesions were studied. The lesioned animals received fetal cortical grafts, obtained from 16-day-old fetuses, and were retrained in the behavioral procedure after 15, 30, 45, or 60 days postgraft. Behavioral results showed a very good functional recuperation at 60 days, slight recovery at 45 and 30 days, and a poor recovery at 15 days postgraft. Results with HRP histochemistry revealed that at 30, 45, and 60 days postgrafting there were increased connections with the ventromedial nucleus of the thalamus and with the amygdala. At 15 days postgrafting there was an absence of HRP-labeled cells. In addition, behavioral recovery was correlated with increased acetylcholinesterase activity, detected histochemically, and with morphological neuronal maturation, revealed by Golgi staining. These results suggest that morphological maturity and reconnectivity between grafts and host tissue are important for behavioral recovery in gustatory neocortex-lesioned rats.

Acetylcholinesterase↗

PubMed1990

Fetal brain transplants induce recovery of male sexual behavior in medial preoptic area-lesioned rats.

Male rats received bilateral lesions within the medial preoptic area which completely abolished sexual behavior. Hypothalamic fetal brain transplants gradually restored sexual behavior to prelesion levels by the 6th week after the transplant. Immunocytochemical analyses revealed tyrosine hydroxylase immunoreactivity neurons within the transplanted tissue. These results demonstrate that fetal brain transplants can restore an innate complex behavior in which no spontaneous recovery is observed.

Animals↗

PubMed1990

Release of acetylcholine, gamma-aminobutyrate, dopamine and glutamate, and activity of some related enzymes, in rat gustatory neocortex.

The gustatory neocortex (GN), final relay along the gustatory pathway, is a region of the brain involved in the neural integration of feeding behavior. Since information on the neurotransmitters in this nucleus is scarce, the aim of the present work was to establish whether acetylcholine (ACh), gamma-aminobutyric acid (GABA), dopamine and glutamate may act as transmitters within this structure. It was found that GN slices are able to release labeled GABA, ACh and glutamate but not dopamine. Additionally, it was possible to detect significant glutamic acid decarboxylase, choline acetyltransferase and acetylcholinesterase activities in GN homogenates. The activity of the two enzymes involved in acetylcholine metabolism was higher than that observed in other cortical regions. These findings suggest that GABA, ACh and glutamate probably are neurotransmitters in the GN, whereas dopamine is not.

Acetylcholine↗

PubMed1990

Correlation between acetylcholine release and recovery of conditioned taste aversion induced by fetal neocortex grafts.

Rats with lesions of the gustatory neocortex (GN) show deficits in the acquisition of taste aversion. Fetal GN grafts to a lesioned animal restore taste aversion learning and establish connections with the host brain. In this work, we examined whether the grafts are biochemically functional and whether this fact can be related to behavioral recovery. Gustatory or occipital cortices from rat fetuses were transplanted to GN-lesioned rats. Two months later, taste aversion recovery was tested and the release of labeled gamma-aminobutyric acid (GABA), acetylcholine (ACh), dopamine and glutamate from the grafted tissue was assayed. Fetal GN grafts promoted recovery of learning and released GABA, ACh and glutamate in response to K+ depolarization. Occipital cortex grafts did not induce behavioral recovery, although they were capable of releasing GABA. In contrast, these grafts did not release ACh. Moreover, GN-grafted rats in which behavioral recovery was not seen also failed to release ACh. These results are in agreement with previous findings that cholinergic transmission is important in the GN and suggest that ACh may play a role in the graft-mediated behavioral recovery observed in this model.

Acetylcholine↗

PubMed1989

Fetal brain grafts induce recovery of learning deficits and connectivity in rats with gustatory neocortex lesion.

Three groups of rats showing disrupted taste aversion due to gustatory neocortex lesions, were studied. One group received a transplant of homotopic cortical tissue, another of heterotopic tectal tissue, obtained from 17-day-old fetuses. The third group remained without transplant as a lesioned control group. Comparisons of the taste aversion scores before and after graft, revealed that cortical grafted animals significantly improved the taste aversion, whereas those which received tectal grafts, and the cortical-lesioned controls did not. Moreover, results with horseradish peroxidase (HRP) histochemistry revealed that the homotopic, but not the heterotopic, brain transplants were able to re-establish connections with amygdala and with the ventromedial nucleus of the thalamus areas who normally kept connectivity with the gustatory neocortex. These results support the hypothesis that fetal brain transplants can reestablish cognitive functions, as well as connectivity with its host tissue.

Amygdala↗

PubMed1987

Fetal brain transplants induce recuperation of taste aversion learning.

Rats showing disrupted taste aversion due to gustatory neocortex or amygdala lesions were transplanted into the lesioned area with homologous brain tissue obtained from 17-day-old fetuses. Comparisons of taste aversions scores before and after the graft, revealed that the grafted animals significantly recuperated taste aversions, whereas cortical lesioned animals without grafts did not. Surprisingly, however, amygdala-lesioned animals without graft presented spontaneous recovery. These results not only support the hypothesis that fetal brain transplants can restore cognitive functions, but also that there are some fundamental functional differences between the gustatory neocortex and the amygdala in the regulation of the processes involved in the acquisition and retention of taste aversion.

Amygdala↗

PubMed1987

Potentiation of odor by taste and odor aversions in rats are regulated by cholinergic activity of dorsal hippocampus.

Limbic cholinergic activity is critically involved in the retention of learned aversions tasks. The purpose of these experiments was to assess the role of cholinergic mechanisms of the dorsal hippocampus in the acquisition of both odor and potentiated odor aversions through taste aversion. Cholinergic activity was increased by physostigmine (Phys). When Phys was applied before the presentation of an odor-taste compound during acquisition, the potentiation of odor-aversion was disrupted, while taste aversion was left intact. When hippocampal cholinergic activity was reduced with the muscarinic antagonist scopolamine (Scop), enhancement of potentiated odor aversion was observed, again with no effect on taste aversion. Moreover, when Phys was applied before an odor alone it also disrupted odor avoidance in two different odor tests conditioning situations, i.e., odor was followed immediately by lithium chloride or foot shock. Neither Scop nor Phys had any effect on taste or potential odor aversions when applied to fronto-parietal cortex. These results suggest that cholinergic activity of the hippocampus is involved in the acquisition of odor aversion conditioning.

Animals↗