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M L Escobar

Publications and source records attributed to M L Escobar.

12 recordsLinked to original sources

Fine structural and cytochemical analysis of the processes of cell death of oocytes in atretic follicles in new born and prepubertal rats.

The process of cell death of oocytes was studied in atretic ovarian follicles of rats aged from 1 to 28 days using light and electron microscope and cytochemical methods. These methods were TUNEL procedure for DNA breaks, active caspase-3 and lysosome-associated membrane protein 1 (LAMP-1) immunolocalizations. The structural features of the process of oocyte death are mainly characterized by the presence of abundant clear vacuoles and autophagosomes, as well as by the absence of large clumps of compact chromatin associated to the nuclear envelope and apoptotic bodies. These features are common to oocytes in all types of follicles studied. Cytochemical features consisting in positive reactions to TUNEL method, active caspase-3 and LAMP-1 immunolocalizations, are common to the cell death of oocytes in all types of follicles. Particular features of the process of cell death of oocytes are found in different types of follicles. Two morphological patterns of cell death occur in pre-follicular oocytes of the new born and in primordial follicles in 1 to 5 days old rats. One is distinguished by clear nucleoli and moderate compaction of chromatin in clumps frequently resembling meiotic bivalents. The second pattern is characterized by nucleolar condensation and by the absence of compact chromatin. The process of cell death of oocytes in antral follicles is characterized by ribonucleoprotein ribbon-like cytoplasmic structures, pseudo-segmentation, and loss of contact with granulosa cells.

Age Factors↗

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↗

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↗

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↗

The NMDA receptor antagonist CPP impairs conditioned taste aversion and insular cortex long-term potentiation in vivo.

It has been proposed that long-term potentiation (LTP) a form of activity-dependent modification of synaptic efficacy, may be a synaptic mechanism for certain types of learning. Recent studies on the insular cortex (IC) a region of the temporal cortex implicated in the acquisition and storage of conditioned taste aversion (CTA), have demonstrated that tetanic stimulation of the basolateral nucleus of the amygdala (Bla) induce an N-methyl-d-aspartate (NMDA) dependent LTP in the IC of adult rats in vivo. Here we present experimental data showing that intracortical administration of the NMDA receptor competitive antagonist CPP (-3(-2 carboxipiperazin-4-yl)-propyl-1-phosphonic acid) disrupts the acquisition of conditioned taste aversion, as well as, the IC-LTP induction in vivo. These findings are of particular interest since they provide support for the view that the neural mechanisms underlying NMDA dependent neocortical LTP, constitute a possible mechanism for the learning related functions performed by the IC.

Animals↗

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↗

Opioid receptor modulation of mossy fiber synaptogenesis: independence from long-term potentiation.

Long-term potentiation (LTP) at the mossy fiber-CA3 synapse of the rat hippocampus is an NMDA receptor-independent form of synaptic plasticity that is sensitive to opioid receptor antagonists [12]. In the present study, Timm's stain, a zinc detecting histological marker commonly used to infer synaptogenesis in the mossy fiber projection, was used to examine whether synaptogenesis occurs in response to mossy fiber LTP induction in the adult rat in vivo. Seven days following the induction of mossy fiber LTP by non-seizure-inducing high-frequency stimulation of the mossy fibers, a prominent band of Timm's staining appeared bilaterally in the infrapyramidal region of the stratum oriens in area CA3. Staining was more prominent on the side contralateral to the stimulation. Systemic administration of the opioid receptor antagonist naloxone, sufficient to block mossy fiber LTP induction, did not block the development of Timm's staining in the infrapyramidal region ipsilateral to stimulation, but it did block stimulation-induced increases in Timm's staining observed contralaterally. Systemic administration of (+/-) CPP, a competitive NMDA receptor-antagonist, by contrast, did not block the induction of LTP and did not alter the increase in Timm's staining observed either ipsilaterally or contralaterally. The increase in Timm's staining in the infrapyramidal region suggests that mossy fiber synaptogenesis occurs in response to non-seizure inducing stimulation. Synaptogenesis does not appear to be directly related to opioid receptor-dependent mossy fiber LTP induction, because it occurs in the presence of naloxone which blocks LTP. The mossy fiber synaptogenesis occurring contralaterally appears to be regulated by endogenous opioid peptides, because it is blocked by naloxone.

Animals↗

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↗

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↗

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↗

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↗

Nerve growth factor with insular cortical grafts induces recovery of learning and reestablishes graft choline acetyltransferase activity.

Rats showing disrupted taste aversion due to insular cortex (IC)-lesions received either IC-grafts with NGF, grafts without NGF, or NGF alone. An additional group served as lesioned controls. Only those animals that received IC-grafts with NGF recovered the ability to learn the conditioned taste aversion task, at 15 days post-graft. Choline acetyltransferase (ChAT) activity in the IC-grafts with, but not without NGF, was similar to the IC activity of unoperated controls. In contrast, glutamate decarboxylase activity was similar in all the groups. These findings suggest that IC-grafts associated with NGF induce recovery of learning abilities in IC-lesioned rats, which correlates with reestablishment of ChAT activity in the grafts at 15 days post-implantation.

Animals↗