Biomedical subjects

J A Bergado

Publications and source records attributed to J A Bergado.

10 recordsLinked to original sources

PubMed2006

Subcortical deafferentation impairs behavioral reinforcement of long-term potentiation in the dentate gyrus of freely moving rats.

Long-term potentiation is a form of neural functional plasticity which has been related with memory formation and recovery of function after brain injury. Previous studies have shown that a transient early-long-term potentiation can be prolonged by direct stimulation of distinct brain areas, or behavioral stimuli with a high motivational content. The basolateral amygdala and other subcortical structures, like the medial septum and the locus coeruleus, are involved in mediating the reinforcing effect. We have previously shown that the lesion of the fimbria-fornix--the main entrance of subcortical afferents to the hippocampus--abolishes the reinforcing basolateral amygdala-effects on long-term potentiation in the dentate gyrus in vivo. It remains to be investigated, however, if such subcortical afferents may also be important for behavioral reinforcement of long-term potentiation. Young-adult (8 weeks) Sprague-Dawley male rats were fimbria-fornix-transected under anesthesia, and electrodes were implanted at the dentate gyrus and the perforant path. One week after surgery the freely moving animals were studied. Fimbria-fornix-lesion reduced the ability of the animals to develop long-term potentiation when a short pulse duration was used for tetanization (0.1 ms per half-wave of a biphasic stimulus), whereas increasing the pulse duration to 0.2 ms per half-wave during tetanization resulted in a transient early-long-term potentiation lasting about 4 h in the lesioned animals, comparable to that obtained in non-lesioned or sham-operated control rats. In water-deprived (24 h) control animals, i.e. in non-lesioned and sham-operated rats, early-long-term potentiation could be behaviorally reinforced by drinking 15 min after tetanization. However, in fimbria-fornix-lesioned animals long-term potentiation-reinforcement by drinking was not detected. This result indicates that the effect of behavioral-motivational stimuli to reinforce long-term potentiation is mediated by subcortical, heterosynaptic afferents.

Afferent Pathways↗

PubMed2003

The amygdala is part of the behavioural reinforcement system modulating long-term potentiation in rat hippocampus.

Long-term potentiation (LTP) in the dentate gyrus can be modulated and prolonged by emotional/motivational influences when concurrently activated. A similar effect on LTP can be obtained by stimulating the amygdala, suggesting that this limbic structure might be part of the neural system involved in behavioural reinforcement. To confirm this we have performed a series of experiments in which the basolateral amygdala was either temporary inactivated by injection of lidocaine or permanently lesioned electrolytically. Both manipulations completely blocked the reinforcing effect of a motivational stimulus (drinking after 24-h deprivation) on LTP at the perforant pathway-dentate gyrus synapses, whilst leaving intact the non-reinforced potentiation. These results demonstrate that the basolateral amygdala is a key structure within the system involved in the modulatory interaction between the affective status of the animal and the mechanisms of functional plasticity.

Amygdala↗

PubMed2003

Modulation of late phases of long-term potentiation in rat dentate gyrus by stimulation of the medial septum.

The prolonged maintenance of hippocampal long-term potentiation (LTP) seems to require heterosynaptic events during its induction. We have previously shown that stimulation of the basolateral nucleus of the amygdala (BLA) within a distinct time window can reinforce a transient early-LTP into a long-lasting late-LTP in the dentate gyrus (DG) in freely moving rats. We have shown that this reinforcement was dependent on beta-adrenergic and/or muscarinergic receptor activation and protein synthesis. However, since the BLA does not directly stimulate the DG the question remained by which inputs such heterosynaptic processes are triggered. We have now directly stimulated the medial septal pathway 15 min after induction of early-LTP in the DG and show that this input is capable of reinforcing early into late-LTP in a frequency-dependent manner. This septal reinforcement of DG LTP was dependent on beta-adrenergic receptor activation and protein synthesis. We suggest that the reinforcing effect of the BLA stimulation can, potentially, be mediated via the septal input to the DG, though it differs in its ability to induce or modulate functional plasticity.

Adrenergic beta-Antagonists↗

PubMed2001

Behavioral reinforcement of long-term potentiation is impaired in aged rats with cognitive deficiencies.

Behavioral stimuli with emotional/motivational content can reinforce long-term potentiation in the dentate gyrus, if presented within a distinct time window. A similar effect can be obtained by stimulating the basolateral amygdala, a limbic structure related to emotions. We have previously shown that aging impairs amygdala-hippocampus interactions during long-term potentiation. In this report we show that behavioral reinforcement of long-term potentiation is also impaired in aged rats with cognitive deficits. While among young water-deprived animals drinking 15 min after induction of long-term potentiation leads to a significant prolongation of potentiation, cognitively impaired aged rats are devoid of such reinforcing effects. In contrast, a slight but statistically significant depression develops after drinking in this group of animals. We suggest that an impaired mechanism of emotional/motivational reinforcement of synaptic plasticity might be functionally related to the cognitive deficits shown by aged animals.

Aging↗

PubMed2000

Synaptic plasticity is impaired in rats with a low glutathione content.

Long-term potentiation (LTP) is a sustained increase in the efficacy of synaptic transmission, based on functional changes involving pre- and postsynaptic mechanisms, and has been considered a cellular model for learning and memory. The sulphurated tripeptide glutathione acts as a powerful antioxidant agent within the nervous system. Recent in vitro studies suggest that the cellular redox status might influence the mechanisms involved in synaptic plasticity. It is not known, however, how glutathione depletion might affect LTP. In the present study, we evaluated the input-output relationships, LTP, and paired-pulse interactions in rats with low glutathione levels induced by systemic injection of diethylmaleate. Our results in anesthetized rats show that the basic synaptic transmission between the perforant pathway and the dentate gyrus granule cells was not affected by glutathione depletion. However, in the same synapses it was not possible to induce prolonged changes in synaptic efficacy (LTP). Paired-pulse facilitation was also absent in the treated animals, suggesting an impairment of short-term synaptic interactions. These findings indicate that low content of glutathione can impair short-term and long-term mechanisms of synaptic plasticity and stress the importance of the redox balance in the normal function of brain circuitry.

Animals↗

PubMed1998

Nerve growth factor improves evoked potentials and long-term potentiation in the dentate gyrus of presenile rats.

Chronic infusion of nerve growth factor (NGF, 1.2 microg/day) for 14 days to presenile rats (17 months at the beginning of treatment) that showed an initial cognitive impairment led to an improved long-term potentiation in the dentate gyrus. Both the relative increase of the slope of the population excitatory postsynaptic potential and that of the population spike were enhanced by NGF pretreatment after long-term potentiation induction at 400 Hz. The treatment was also able to increase the diminished baseline amplitude of the population spike, an effect not seen when the treatment was applied to older animals [Bergado, J., Fernández, C.I., Gómez-Soria, A., González, O., 1997a. Chronic intraventricular infusion with NGF improves LTP in old cognitively-impaired rats. Brain Res. 770, 1-9] stressing the importance of an early start of trophic therapy to achieve better results.

Animals↗

PubMed1997

Chronic intraventricular infusion with NGF improves LTP in old cognitively-impaired rats.

Aged (21 months) cognitively-impaired male Sprague-Dawley rats received intraventricular infusion of nerve growth factor (NGF) or cytochrome C (Cit C) for 14 or 28 days using miniosmotic pumps and were evaluated either 1 week or 3 months after treatment. Groups of untreated young, aged-impaired and aged non-impaired rats were also evaluated. Under narcose recording and stimulating electrodes were stereotactically implanted in the dentate gyrus and the perforant path. The stimulation intensity was individually adjusted to obtain a half-maximal population spike (P) for test stimuli and a quarter-maximal for tetanization. The amplitude and latency of P and the slope (S) of the field EPSP were determined before and at 2, 5, 15, 30 and 60 min after tetanization at 400 Hz. Paired stimuli at 30 ms interval were also applied before and after tetanization. Aged, cognitively impaired rats showed an absent S potentiation and a delayed P potentiation, both in amplitude and latency, while non-impaired rats behaved like the young controls. Paired pulse inhibition showed no difference among groups before or after tetanization suggesting that the impaired potentiation is not due to an increased retroactive inhibition. NGF treatment ameliorates LTP deficits to levels equivalent to non-impaired rats, while Cit C controls showed no improvement. No differences appear among NGF treated groups, but evidence suggest that the animals evaluated 3 months after treatment developed a stronger potentiation.

Aging↗

PubMed1996

Fimbria-fornix lesion impairs long-term potentiation in the dentate gyrus of the rat.

Bilateral aspiration lesions of the fimbria-fornix were performed in 10 male Sprague Dawley rats weighing 240-300 g under chloral hydrate narcose (420 mg/kg). Another 9 animals were operated in the same way, but no aspiration was carried out to constitute a control group. A week after surgery recording and stimulation electrodes were lowered to the dentate gyrus and the perforant path respectively, using the same narcose. After tetanic stimulation (10 trains at 400 Hz) a potentiation of the population spike develops in both groups, but the slope of the excitatory postsynaptic potential showed no potentiation in the lesioned group. Acetylcholinesterase histochemistry confirmed a severe reduction of the cholinergic innervation to the hippocampal formation, suggesting a causal relationship to the deficits seen in long-term potentiation. This impaired potentiation could be related to the memory deficits reported for fimbria-fornix lesioned rats. Such pattern of potentiation deviates from what has been described for aged, memory deficient rats, but closely corresponds to the changes described in infantile rats.

Acetylcholinesterase↗

PubMed1988

Orotate improves memory and enhances synaptic long-term potentiation in active avoidance behaviour in rats with perforant path stimulation as the conditioned stimulus.

Male Wistar rats were trained in an active avoidance task with stimulation of the perforant path with impulse trains of 15 Hz as the conditioning stimulus. Immediately after the first training session, methylglucamine orotate (225 micrograms), a memory improving drug, was injected intraventricularly. The retention of the learned behaviour was determined on the following day in a relearning session. Field potentials evoked in the dentate area by test stimuli from the perforant path electrode were recorded at different times after learning and relearning sessions to determine whether there were functional changes in the perforant path-granular cell synapses, which are involved in the conditioning pathway. Untreated control animals exhibited a so-called 'postconditioning potentiation', expressed as a long-lasting increase of both the excitatory postsynaptic potential (EPSP) and the population spike of the granular cells of the evoked test potentials. This finding reproduces previously published results. Methylglucamine orotate-treated rats showed significantly more conditioned reactions in the relearning sessions compared with untreated controls and a significantly more pronounced potentiation of the population spike, whereas the postconditioning potentiation of the field EPSP remained unaffected by the treatment. When both the control animals and the methylglucamine orotate-treated rats were divided into subgroups of good and poor learners according to their learning scores from the first training session, differences between the effect of the drug became evident. In good learners, the treatment with methylglucamine orotate after the learning session slightly, but significantly, improved retention compared with that of untreated good learners.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Septal fetal tissue transplants restore long-term potentiation in the dentate gyrus of fimbria-formix-lesioned rats.

Two groups of Sprague-Dawley male rats received bilateral aspirative lesions of the fimbria fornix under chloral hydrate anesthesia. One group (n = 9) received no further treatment (lesioned). In the second group (n = 8), a piece of septal fetal tissue, obtained at day E15-16, was implanted into each lesion cavity (transplanted). A third group consisted of shamlesioned rats (controls, n = 14). Two months after the operations, a recording electrode was implanted in the hilar region of the dentate gyrus of each animal, and a bipolar stimulating electrode was implanted in the perforant path. Long-term potentiation at 400 Hz was induced and followed for two hours. FF-lesioned rats showed an impaired potentiation of the field excitatory post-synaptic potential, which rapidly declined to basal levels within 15 minutes. The transplanted rats showed a normal potentiation of this parameter, similar to that seen in the control animals. A decrease in choline acetyltransferase activity in the hippocampi of the lesioned animals showed a tendency toward recovery after septal fetal tissue transplantation. In all the dorsal hippocampal areas of the lesioned animals, acetylcholinesterase histochemistry showed an almost complete loss of enzymatic activity, which was partially restored by the transplants. The improved synaptic plasticity in the transplanted animals might be related to septal transplant-induced recovery of mnemonic functions.

Acetylcholinesterase↗