BDNF in quinolinic acid lesioned rats after bone marrow cells transplant.

Brain-derived neurotrophic factor (BDNF) concentration was measured in the striatum and cortex after quinolinic acid intrastriatal lesion and transplantation of bone marrow cells (BMSC). The results showed a significant increase of the BDNF levels in the striatum and cortex of the lesioned animals and the ability of the transplanted cells to increase the levels of BDNF in both sites. This recovery of BDNF production and distribution might have beneficial effects and ameliorate the negative consequences of the striatal lesion, a mechanism of potential interest for the treatment of Huntington's disease (HD).

Electrical and pharmacological manipulations of the nucleus accumbens core impair synaptic plasticity in the dentate gyrus of the rat.

The interest on the physiology of the nucleus accumbens (NAcc) has grown in recent years given its relationship to addictive behaviours, and the possibility to treat them by interacting with NAcc function. We have shown that the prior stimulation of the core region blocks induction of long-term potentiation (LTP) at the dentate gyrus in anaesthetized rats, while the shell facilitated it. In the present study we have confirmed and expanded those results testing the effects of core and shell stimulation in freely moving rats, as well as the effect of blocking D1 receptors in the NAcc. Our results show that shell stimulation had no effect on baseline recordings of the field excitatory postsynaptic potential (fEPSP) or the population spike amplitude (PSA) for 24 h. Core stimulation did not modify baseline-fEPSP, but significantly depressed PSA up to 8 h. LTP maintenance was not modified; neither by core nor shell stimulation after its induction, but LTP induction was impaired (both in the fEPSP and PSA) by core stimulation 15 min before induction. Shell stimulation showed a slight facilitating effect. Previous, topical application of a dopaminergic-receptor antagonist (SCH23390) into the NAcc produced a significantly depressed baseline fEPSP and PSA, as well as LTP measured in both components of the evoked potentials. Our results confirm a dual role of stimulation of NAcc sub-regions on hippocampal baseline synaptic transmission, and LTP induction when activated before induction. In contrast, stimulation of the NAcc had no influence on an already ongoing dentate gyrus LTP. A role for dopaminergic innervation to the NAcc, modifying susceptibility for synaptic plasticity outside the NAcc is also suggested by our results.

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.

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.

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.

Fimbria-fornix lexion impairs long-term potentiation in the dentage 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 hydratenarcose (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

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