Marisa Arnedo

The functional relevance of the lateral parabrachial nucleus in lithium chloride-induced aversion learning

Lesions to the lateral parabrachial nucleus (PBN), one of the subnuclei that make up the pontine parabrachial complex, impairs the acquisition of taste aversion learning (TAL) with LiCl as the toxic stimulus. In this experiment, PBNl-lesioned and control rats were trained to learn a delayed task with a 15-min interval between presentation of the gustatory and the aversive stimulus. The impairment in learning observed after lesions of the PBNl is discussed in terms of disruption of the transmission of toxic stimuli (LiCl) processed by the humoral pathway and the area postrema (AP).

Temporal orienting deficit after prefrontal damage

The aim of this study was to explore, for the first time in patients, the neural bases of temporal orienting of attention as well as the interrelations with two other effects of temporal preparation: the foreperiod effect and sequential effects. We administered an experimental task to a group of 14 patients with prefrontal lesion, a group of 15 control subjects and a group of 7 patients with a basal ganglia lesion. In the task, a cue was presented (a short versus long line) to inform participants about the time of appearance (early versus late) of a target stimulus, and the duration of the cue-target time intervals (400 versus 1400 ms) was manipulated. In contrast to the control group, patients with right prefrontal lesion showed a clear deficit in the temporal orienting effect. The foreperiod effect was also affected in the group of patients with prefrontal lesion (without lateralization of the deficit), whereas sequential effects were preserved. The group of basal ganglia patients did not show deficits in any of the effects. These findings support the voluntary and strategic nature of the temporal orienting and foreperiod effects, which depend on the prefrontal cortex, as well as the more automatic nature of sequential effects, which do not depend on either prefrontal cortex or frontobasal circuits.

Lesions of the lateral parabrachial nuclei disrupt aversion learning induced by electrical stimulation of the area postrema

The research about the neural basis of taste aversion learning (TAL) has pointed out the area postrema (AP) as a fundamental structure implied in the processing of certain toxic stimuli. Likewise, recent studies demonstrated that electric stimulation of the AP is an efficient substitute of the aversive stimulus. The lateral parabrachial nucleus (PBN1), one of the subnuclei of the parabrachial complex, is the main anatomic rostral connection of the AP. In the experiment presented here, we demonstrate that TAL induced by electric stimulation of the AP is interrupted when the PBN1 is lesioned, thus giving support to the functional role of this anatomic system (AP-PBN1) in the codification of aversive stimuli processed by the AP.

Electrical intracerebral stimulation of the area postrema on taste aversion learning.

The structural characteristics of the area postrema, its anatomical connections, participation in the detection of emesis-provoking substances and the effects of area postrema lesions on taste aversion learning acquisition, are all factors which speak in favor of a role as a chemoreceptor zone involved in the detection of aversive agents which act as effective inducers of taste aversion learning. The feasibility of substituting electrical intracerebral stimulation of the area postrema for the aversive stimulus was investigated in a taste aversion learning paradigm. In Expt. 1, 0.1-ms rectangular pulses of 50 Hz, delivered intermittently or continuously for 4 h after a 15-min delay following ingestion of the gustatory stimulus, produced reliable learning. Expt. 2 showed the learning thus induced to reflect all the characteristics features attributed to taste aversion learning: one-trial learning, long interstimulus delay and cue-consequence specificity. These results suggest that the area postrema could participate in the detection of the aversive consequences of particular taste aversion learning-inducing agents.

Effects of medullary afferent vagal axotomy and area postrema lesions on short-term and long-term NaCl-induced taste aversion learning

This series of experiments demonstrates a functional dissociation between the area postrema (AP) and the vagus nerve in short-term taste aversion learning (TAL). Although medullary axotomy of the afferent component of the vagus disrupted the learning observed with NaCl-induced short-term (nondelayed) TAL, lesioning the AP failed to interfere with the discriminative process employed by the animals under the same conditions. However, involvement of neither the vagus nerve nor the AP seemed to be indispensable for learning in NaCl-induced long-term (delayed) TAL. The possibility that the vagus nerve and the AP are involved in temporally distinct visceral processing is discussed.

The functional relevance of the area postrema in drug-induced aversion learning

Research into the neural mechanisms involved in the acquisition of learned aversions induced by drug points toward the area postrema (AP) as one of the structures implicated in the detection of drug aversive consequences. The evidence suggest that although the AP is indeed involved in drug-induced learned aversions, its functional integrity is not always a necessary requisite for learning to take place. The aim in this study was to determine whether the AP is essentially or selectively involved in all learned aversions induced by scopolamine methyl nitrate (SMN) using different number of trials with the aversive stimulus. In Experiment 1, AP-lesioned rats were injected with SMN fifteen minutes after consuming a flavoured solution during three consecutive trials. A single-stimulus test failed to detect learned aversions, which were, however, evident in two subsequent choice-tests. In one-trial paradigms, however, choice-tests as well as single-stimulus tests failed to detect learned aversions in AP-lesioned rats, both when SMN was injected immediately after stimulus intake (Experiment 2) and when a fifteen-minute delay was introduced (Experiment 3). The results suggested that the AP is not essential for the acquisition of SMN-induced aversion learning with three consecutive trials if learning is detected with a choice-test, although effective single-trial learning does apparently require a functional AP.

Rhythms can overcome temporal orienting deficit after right frontal damage

The main aim of this study was to test whether the use of rhythmic information to induce temporal expectations can overcome the deficit in controlled temporal preparation shown by patients with frontal damage (i.e. temporal orienting and foreperiod effects). Two tasks were administered to a group of 15 patients with a frontal brain lesion and a group of 15 matched control subjects: a Symbolic Cued Task where the predictive information regarding the time of target appearance was provided by a symbolic cue (short line-early vs. long line-late interval) and a Rhythm Cued Task where the predictive temporal information was provided by a rhythm (fast rhythm-early vs. slow rhythm-late interval). The results of the Symbolic Cued Task replicated both the temporal orienting deficit in right frontal patients and the absence of foreperiod effects in both right and left frontal patients, reported in our previous study (Triviño, Correa, Arnedo, & Lupiañez, 2010). However, in the Rhythm Cued Task, the right frontal group showed normal temporal orienting and foreperiod effects, while the left frontal group showed a significant deficit of both effects. These findings show that automatic temporal preparation, as induced by a rhythm, can help frontal patients to make effective use of implicit temporal information to respond at the optimum time. Our neuropsychological findings also provide a novel suggestion for a neural model, in which automatic temporal preparation is left-lateralized and controlled temporal preparation is right-lateralized in the frontal lobes.

The functional relevance of medial parabrachial nucleus in intragastric sodium chloride-induced short-term (concurrent) aversion learning.

The functional meaning of the visceral information processing in the medial parabrachial nucleus (PBNm) was analyzed in this study through a short-term aversion learning task. In this short-term task the animals (Wistar rats) had to learn to discriminate between two different gustatory-olfactory stimuli presented simultaneously (two graduated burettes); one of the stimuli was associated with the concurrent intragastric administration of an aversive chemical agent (hypertonic NaCl) and the other stimulus was paired with no injection. In the first experiment, the PBNm-lesioned animals are unable to learn the task using gustatory stimuli (saccharin and quinine) that surpassed the detection threshold of parabrachial-lesioned rats. Moreover, in a second experiment, the PBNm-lesioned animals were unable to learn the task when there was no initial preference for either of the gustatory-olfactory stimuli presented (strawberry or coconut). However, this short-term task is learned by lateral parabrachial nucleus (PBNl) lesioned animals. The possibility that the PBNm and the PBNl are involved in distinct mechanisms of visceral processing is discussed.

Effects of lesions of the medial parabrachial nucleus (PBNm) : Taste discrimination and lithium-chloride-induced aversion learning after delayed and contiguous interstimulus intervals

This article analyzes the effects of lesions to the medial parabrachial nucleus (PBNm) in taste aversion learning (TAL) and taste discrimination tasks (TDT). In the first experiment, control and lesioned rats were presented with a delayed TAL task in which presentation of the gustatory stimulus was followed 15 min later by the intragastric administration of LiCl. In the second experiment, ingestion of the gustatory stimulus was followed immediately by LiCl administration. Control animals successfully learned both tasks, whereas PBNm-lesioned animals learned only the second task. In the third experiment, the animals were subjected to TDT with water, saccharine, and quinine. The lesioned animals ingested significantly different amounts of stimuli from that ingested by control rats, showing a clear preference for high concentrations of saccharine; the lesioned animals rejected high concentrations of quinine to a lesser degree than did control animals. In a fourth experiment, PBNm-lesioned animals were able to solve a delayed TAL task when discriminated gustatory stimuli were used. These results are interpreted as evidence that the PBNm lesion interferes with gustatory processing and that the temporal demands imposed by Experiment 1 obviate the use of exteroceptive cues.

Participation of the area postrema in learned aversions induced by body rotation.

Existing data on the effects of area postrema (AP) lesions on body rotation-induced emesis as well as on the participation of this zone in the acquisition of taste aversion learning (TAL) with other emetic agents suggest a possible role for the AP in learned aversions induced by body rotation. Nevertheless, earlier studies have shown that AP lesions do not prevent learned aversions induced by body rotation. The present experiments were performed in male Wistar rats in order to explore the effects of AP lesions on body rotation-induced flavor aversions as a function of the paradigm employed. Flavor aversions were induced by 30 min of circular body rotation (90 r.p.m.) using two different paradigms: a standard one including one trial learning, delay and single stimulus test and a three trials paradigm (with and without interstimulus delay) including both single stimulus test and choice test. AP lesions disrupt acquisition provided that the paradigm used includes interstimulus delay, i.e. when body rotation is applied 15 min after flavor intake. However, the AP seems to play no essential role when body rotation is applied immediately after flavor intake in a three-trial paradigm, as no effects were observed following AP lesions. In addition, subdiaphragmatic vagotomy plus simultaneous AP lesions leads to no interference in the acquisition of learned aversions induced by body rotation applied immediately after intake. It is concluded that body rotation may trigger a variety of aversive effects capable of inducing learned aversions, each apparently involving independent neural systems.