Anna Vale-Martínez

Electrolytic and ibotenic acid lesions of the nucleus basalis magnocellularis interrupt long-term retention, but not acquisition of two-way active avoidance, in rats

Abstract. Previous experiments on two-way active avoidance have shown conflicting results after nucleus basalis magnocellularis lesion: disrupting effects with electrolytic lesions and facilitative effects with excitotoxic lesions. To resolve this issue, in this experiment, Wistar rats received pre-training bilateral electrolytic or ibotenic acid lesions and were trained in a massed two-way active avoidance conditioning. In order to test the long-term retention of the learned response, one additional session was conducted 10 days after the acquisition. Results showed that whereas electrolytic lesions did not affect the acquisition, ibotenic acid lesions enhanced it. Retention of active avoidance response was impaired by both electrolytic and ibotenic lesions of the NBM. These results suggest a role of the NBM in the memory consolidation and/or retrieval of two-way active avoidance.

Muscarinic receptor blockade in ventral hippocampus and prelimbic cortex impairs memory for socially transmitted food preference.

Acetylcholine is involved in learning and memory and, particularly, in olfactory tasks, but reports on its specific role in consolidation processes are somewhat controversial. The present experiment sought to determine the effects of blocking muscarinic cholinergic receptors in the ventral hippocampus (vHPC) and the prelimbic cortex (PLC) on the consolidation of social transmission of food preference, an odor‐guided relational task that depends on such brain areas. Adult male Wistar rats were bilaterally infused with scopolamine (20 μg/site) immediately after social training and showed impairment, relative to vehicle‐injected controls, in the expression of the task measured 24 h after learning. Results indicated that scopolamine in the PLC completely abolished memory, suggesting that muscarinic transmission in this cortical region is crucial for consolidation of recent socially acquired information. Muscarinic receptors in the vHPC contribute in some way to task consolidation, as the rats injected with scopolamine in the vHPC showed significantly lower trained food preference than control rats, but higher than both chance level and that of the PLC‐injected rats. Behavioral measures such as social interaction, motivation to eat, neophobia, or exploration did not differ between rats infused with scopolamine or vehicle. Such data suggest a possible differential role of muscarinic receptors in the PLC and the vHPC in the initial consolidation of a naturalistic form of nonspatial relational memory.

Effects of electrical stimulation of the nucleus basalis on two-way active avoidance acquisition, retention, and retrieval

This study assessed the role of the nucleus basalis magnocellularis (NBM) in specific memory phases of two-way active avoidance conditioning. We evaluated the effects of NBM electrical stimulation applied during different phases of the avoidance task. Rats were trained in a 30-trial acquisition session, and were tested again 24 and 48 h later. NBM stimulation was applied at different stages of memory formation of the conditioning: (1) immediately before the first training session to determine the effects on acquisition of the two-way avoidance task; (2) immediately after the first training session to evaluate effects on memory consolidation; and (3) immediately before the 24-h retention session to analyze the effects on the retrieval process. NBM stimulation before training significantly improved the acquisition of the task, without affecting subsequent retention at either 24 or 48 h. Stimulation of the NBM immediately after the first training session slightly impaired performance in the 24-h retention session. Stimulation of the NBM immediately before the 24-h retention session did not affect performance in either the 24 or 48-h retention sessions. Therefore, the NBM may play a more important role in acquisition of memory in aversively motivated conditioning tasks than in consolidation or retrieval of such memories. These results are discussed in the context of attention enhancement and cortical and amygdala activation.

Effects of fimbria lesions on trace two-way active avoidance acquisition and retention in rats.

The fimbria-fornix (FF) is the main subcortical input to the hippocampus. It has been shown that FF lesions facilitate performance on a standard-delay two-way active avoidance task (AA2), thought to involve implicit memory. The hippocampal region is required for explicit or relational memory. It has been proposed that the hippocampus and related structures might associate events that are separated in space or time and detect elements shared in common by such discontiguous episodes. Therefore, FF lesions would be expected to impair performance on a trace paradigm, which introduces an interval between the CS (conditioned stimulus) and the US (unconditioned stimulus) and is generally considered a model of explicit memory. We predicted that FF lesions would impair memory in a trace AA2 procedure, while the same lesions would facilitate memory in a standard delay version of the task. To test this hypothesis, two experiments were carried out in 102 male Wistar rats. The first experiment characterized the trace paradigm using this kind of conditioning and demonstrated that control rats were able to acquire and retrieve (24 h and 11 days postacquisition) the association between the CS (tone) and the US (electric foot shock) when a trace interval (5, 10, or 20 s) was interposed between both stimuli. In the second experiment, we investigated the effects of FF electrolytic lesions on the same task using delay and trace (10-s trace interval) paradigms. Surprisingly, FF lesions facilitated the acquisition and the 24-h retention of the AA2 not only on the standard delay paradigm, but also with the trace paradigm. We suggest that facilitative effects could be a result of impairment in contextual learning.

The parafascicular nucleus and two-way active avoidance: effects of electrical stimulation and electrode implantation

Abstract To evaluate whether electrical stimulation of the parafascicular nucleus (PF) can improve short-term (24 h) and/or long-term (21 days) retention of two-way active avoidance, rats were implanted with an electrode at this nucleus (experimental groups) or above it (control groups). After a single 30-trial acquisition session, experimental groups were submitted to a 10-min session of electrical stimulation. Results showed that the simple implantation of an electrode at the posterior PF enhanced by itself the acquisition of two-way active avoidance, in such a way that the subsequent stimulation of this region may have been unable to further improve the performance of the rats. On the other hand, parafascicular stimulation improved the 24-h retention of the task in a site-specific way, since this effect was mainly seen after stimulation of the central PF region. The facilitative effect on 24-h retention could also depend on the level of performance achieved during the acquisition session, because this improvement was only evidenced in poorly learning animals. No effects were found on 21-day retention. The present results confirm the involvement of the PF in learning and memory and the functional heterogeneity of this nucleus.

Muscarinic cholinergic receptor blockade in the rat prelimbic cortex impairs the social transmission of food preference

Previous findings demonstrate the involvement of the cholinergic NBM in the acquisition of the social transmission of food preference (STFP), a relational associative odor-guided learning task. There is also evidence that muscarinic receptors in the medial prefrontal cortex, an important NBM target area, may modulate olfactory associative memory. The present experiment determined the consequences of blocking muscarinic cholinergic receptors in a component of the medial prefrontal region (the prelimbic cortex) on the STFP task. Adult male Wistar rats were bilaterally infused with scopolamine (20 microg/site) prior to training and showed a severe impairment in the expression of the task measured in two retention sessions, both immediately and 24h after training. Local scopolamine injections in the prelimbic cortex did not affect other behavioral measures such as olfactory perception, social interaction, motivation to eat, neophobia, or exploration. Results suggest that muscarinic transmission in the prelimbic cortex is essential for the STFP, supporting the hypothesis that ACh in a specific prefrontal area is important for this naturalistic form of olfactory relational memory. Current data are discussed in the context of disruption of learning as a result of interferences in PLC functions such as behavioral flexibility, attention, and strategic planning.

Nucleus basalis magnocellularis electrical stimulation facilitates two-way active avoidance retention, in rats

We studied the effects of post-training intracranial electrical stimulation of the nucleus basalis magnocellularis on two-way active avoidance retention. After the acquisition, rats were stimulated for 20 min, and they were tested again after 24 h or 11 days. The treatment improved memory consolidation, especially in animals with a low initial learning ability. These facilitative effects could be attributed to an enhancement of cortical and/or amygdala activation, leading to an improvement in associative processes and/or cortical plasticity.

D-cycloserine in the basolateral amygdala prevents extinction and enhances reconsolidation of odor-reward associative learning in rats.

It is well established that D-cycloserine (DCS), a partial agonist of the NMDA receptor glycine site, enhances learning and memory processes. Although the effects of DCS have been especially elucidated in the extinction and reconsolidation of aversive behavioral paradigms or drug-related behaviors, they have not been clearly determined in appetitive tasks using natural reinforcers. The current study examined the effects of pre-retrieval intra-basolateral amygdala (BLA) infusions of DCS on the extinction and reconsolidation of an appetitive odor discrimination task. Rats were trained to discriminate between three odors, one of which was associated with a palatable food reward, and, 20 min prior to extinction learning (experiment 1) or reactivation (experiment 2), they received bilateral intra-BLA infusions of DCS or vehicle. In experiment 1, DCS infusion reduced the rate of extinction learning, weakened extinction retention in a post-extinction test and enhanced reacquisition of the ODT task. In experiment 2, DCS improved subsequent memory expression in the reconsolidation test performed one day after the reactivation session. Such results indicate the involvement of BLA NMDA receptors in odor-food reward associative memory and suggest that DCS may potentiate the persistence or strength of the original memory trace.

Excitotoxic lesions of the parafascicular nucleus produce deficits in a socially transmitted food preference.

The parafascicular (PF) nucleus, a posterior component of the intralaminar nuclei of the thalamus, is considered to be an essential structure in the feedback circuits of basal ganglia-thalamo-cortical systems that critically participate in cognitive processes. To study the PF contribution to processing of behaviorally significant information during specific episodes of learning, we investigated the effects of damaging the PF nucleus in the acquisition of a natural form of social olfactory learning, the socially transmitted food preference (STFP) task. This task is a non-spatial paradigm that exhibits some of the characteristics of relational memory because it requires that animals use information obtained in one episode to guide later behavior in different circumstances. Adult male Wistar rats were submitted to pretraining bilateral N-methyl-D-aspartate (0.15 M, pH 7.4) lesions of the PF (0.4 microl/side, 0.2 microl/min). The behavioral effects of PF lesions were compared to vehicle- and sham-operated control groups and two retention delays were considered in separate groups: immediately (Lesion-I, Vehicle-I, and Sham-I groups) and 24h after training (Lesion-24, Vehicle-24, and Sham-24 groups). PF lesions produced delay-independent impairments in the STFP suggesting that this nucleus might modulate the acquisition of this odor-odor association task. Results are discussed in the context of medial prefrontal cortex deafferentation induced by PF damage.

Effects of Parafascicular Electrical Stimulation and Lesion upon Two-Way Active Avoidance in Rats

To evaluate a possible role of the parafascicular nucleus (PF) in modulating distributed two-way active avoidance acquisition and long-term retention (LTR), we designed two experiments. Experiment I was aimed at checking whether posttraining PF intracranial electrical stimulation (PF ICS) can improve the acquisition and/or the LTR of the task. All subjects (Ss, male Wistar rats) were implanted with an electrode at the PF. After each learning session two groups of Ss were stimulated for 10 (ICS-10 group) and 5 (ICS-5 group) min, respectively. A Control group never received PF ICS, while Ss in an ICS-Control group received PF ICS only during a previous search for a nonconvulsive current intensity. Unexpectedly, the ICS-Control group showed poor performance of the task compared to the remaining groups. Since the histological analyses showed that the pretraining ICS treatment produced some PF tissue lesion, Experiment II was aimed at evaluating the effects upon the same task of (1) pretraining PF electrolytical lesions (PF-Lesion group) and (2) posttraining PF ICS treatment (ICS group) at a lower current intensity and without a previous search for nonconvulsive current intensity. PF pretraining lesion decreased conditioning, while posttraining PF ICS did not affect it. We concluded that PF could have a modulatory role in acquisition, and might also contribute to posttraining consolidation, of a distributed two-way active avoidance.