Variables affecting long-term memory of learning that a food is inedible in Aplysia

Long-term memory of learning that a food is inedible was studied in Aplysia. Seven days after a single training session, animals retained significant memory, as measured by a number of parameters. A 2nd experiment demonstrated savings 3 weeks after 2 training sessions. Long-term memory was also found after training procedures were altered to resemble those more likely to occur in nature, such as training for only 10 min or training with ad-lib access to inedible food, with no experimenter intervention. The effects were determined of bilaterally sectioning the esophageal nerves that innervate the gut. Denervation of the gut blocked the ability to learn that food is inedible but did not affect memory after the task had already been learned.     

Nitric oxide signals that aplysia have attempted to eat, a necessary component of memory formation after learning that food is inedible

Inhibiting nitric oxide (NO) synthesis during learning that food is inedible in Aplysia blocks subsequent memory formation. To gain insight into the function of NO transmission during learning we tested whether blocking NO synthesis affects aspects of feeding that are expressed both in a nonlearning context and during learning. Inhibiting NO synthesis with L-NAME and blocking guanylyl cyclase with methylene blue decreased the efficacy of ad libitum feeding. D-NAME had no effect. L-NAME also decreased rejection responses frequency, but did not affect rejection amplitude. The effect of L-NAME was explained by a decreased signaling that efforts to swallow are not successful, leading to a decreased rejection rate, and a decreased ability to reposition and subsequently consume food in ad libitum feeding. Signaling that animals have made an effort to swallow is a critical component of learning that food is inedible. Stimulation of the lips with food alone did not produce memory, but stimulation combined with the NO donor SNAP did produce memory. Exogenous NO at a concentration causing memory also excited a key neuron responding to NO, the MCC. Block of the cGMP second-messenger cascade during training by methylene blue also blocked memory formation after learning. Our data indicate that memory arises from the contingency of three events during learning that food is inedible. One of the events is efforts to swallow, which are signaled by NO by cGMP.     

Interleukin-10 (IL-10) but not Lipopolysaccharide (LPS) produces increased motor activity and abnormal exploratory patterns while impairing spatial learning in Balb/c mice

Lipopolysaccharide (LPS) is a potent endotoxin, which produces "sickness behaviours" including loss of weight, loss of interest in food and decreased exploration. LPS has also been shown in some studies to cause deficits in various learning and memory abilities, while in others these LPS-induced learning impairments have been attributed to performance-related deficits rather than learning deficits per se. Here, we use the novelty-preference paradigm, a task that minimises performance-related factors such as motivation, in an attempt to extract and examine the effects of LPS on spatial learning. In addition, some studies have indicated that the anti-inflammatory cytokine Interleukin-10 (IL-10) can alleviate some of the symptoms induced by LPS. Here, we also examine the effect of IL-10 on feeding, motor and learning behaviours. We demonstrate that a single injection of LPS does produce a lack of interest in food and weight loss; LPS, however, does not impair habituation in the novelty-preference paradigm. Furthermore, co-injection of IL-10 with LPS does not attenuate the LPS-induced effects of weight loss and lack of food intake. Interestingly, a single injection of IL-10 produces abnormal patterns of exploration, a general increase in activity and abnormal patterns of habituation.     

Chemosensory and hormonal mediation of social memory in male rats

The persistence with which adult male rats investigated a juvenile conspecific was significantly reduced following preexposure to either the juvenile or chemosensory stimuli (soiled bedding or urine) from that juvenile. The reduced persistence did not occur when the chemosensory stimulus came from a juvenile different from the one with which the subject was subsequently tested, which suggests the presence of a chemosensorily mediated social memory. It is suggested that any such memory may have adaptive value in that it permits a male rat to more readily identify a novel conspecific. Also, the lack of reduced persistence of social investigatory behavior in castrated subjects demonstrates the importance of male gonadal hormones in the formation, storage, and/or retrieval of the proposed chemosensorily mediated social memory.     

A comparison of state dependent learning induced by electroconvulsive shock and pentobarbital

Two experiments compared the efficacy of electroconvulsive shock (ECS) and ECS preceded by footshock (FS-ECS) to produce state dependent learning relative to pentobarbital (12 and 25 mg/kg). In Experiment 1, rats were trained in a water T-maze and retrained 72 hr later. Comparison with controls indicated: (a) FS-ECS administered 24 hr prior to training but not retraining (Agent-O order) produced state dependency but did not when animals were trained in the normal state and received FS-ECS 24 hr prior to retraining (O-Agent order) as in most retrograde amnesia experiments; (b) pentobarbital, 12 or 25 mg/kg, injected just prior to either training or retraining produced state dependency in the O-Agent order but not the Agent-O order; and, (c) ECS alone was not effective in either treatment order. Experiment 2 used reversal training to determine the state dependency effect of the agents. Conclusions were the same as in Experiment 1 except that FS-ECS produced state dependency in both treatment orders. These data indicate that FS and ECS interact to produce a dissociation effect 24 hr later that is as complete as that produced shortly after pentobarbital injections. The results of Experiment 2 but not of Experiment 1 support the notion that amnesia observed 24 hr after a training trial FS followed 0.5 sec later by ECS may be due to a state dependency effect rather than the failure of memory fixation.     

Properties of spreading depression-induced consumatory behavior in rats

The present study showed that principally eating can be elicited by unilateral single waves of spreading depression (SD) induced by KCl injections, electrical or mechanical stimulation of the neocortex and hippocampus in rats. In a sample of freely moving rats slow potential and EEG concomitants of SD were recorded. Experiments dealing with SD-induced feeding provided the following results: (a) In the absence of food SD induced lever pressing in satiated animals that had been pretrained to respond under food reinforcement; (b) under SD rats preferred to eat food soaked in water to food soaked in quinine solution; (c) the incidence of SD-induced feeding was decreased in rats pretreated with intragastric glucose or intraperitoneal amphetamine; (d) SD-induced feeding could not be switched to drinking behavior; (e) SD-induced behaviors were not influenced by hypophysectomy.     

Recovery of Memory by the Glutamate NMDA Receptor Agonist D-Cycloserine Depends on the Stage of Development of Amnesia

We have previously observed that in common snails trained to an associative skill consisting of refusing a defined foodstuff, impairment of memory reconsolidation by the NMDA receptor antagonist MK-801 evokes amnesia in which the skill can be recovered by retraining at the early stage (<10 days) while retraining at the late stage does not lead to formation of the skill. In the experiments reported here, amnesia was induced with MK-801 and a reminder 24 h after training of snails to conditioned taste aversion, and the antiamnestic effects of D-cycloserine, a partial agonist of the glycine site of the NMDA receptor, were studied in the early (day 3) and late (day 12) stages. Three days after induction of amnesia, injections of D-cycloserine and a reminder of the conditioned food stimulus led to recovery of the memory; administration of D-cycloserine without a subsequent reminder was ineffective. Injection of D-cycloserine and a reminder 12 days after induction of amnesia had no effect on its development and retraining did not lead to recovery of the memory. Thus, this study is the first to show that the NMDA receptor agonist D-cycloserine influences memory recovery processes only at the early stage of development of amnesia induced by lesioning of reconsolidation processes, while the late stage of amnesia was not sensitive to this agonist.     

Mutual influence of the maternal hen's food calling and feeding behavior on the behavior of her chicks

It is widely accepted that brooding hens attract their chicks to food by food calling, but until now, the concurrent behavior of hens and chicks has never been investigated in depth. This study provides a detailed analysis of both the behavior of brooded chicks and the distance to their mother in relation to her feeding sequences, and whether they contained food calling. Our results revealed that brooding hens utter food calls while pecking, especially when their chicks are not feeding and/or have been at some distance for several seconds. Chicks' response to their mother's feeding activities was more pronounced in the presence than in the absence of food call. Chicks responded to this call by approaching their mother and increasing their pecking; their response became more efficient as they grew older. We thus consider food calls as an arousal vocalization that directs the chicks' attention to a food item chosen by a hen.     

Influence of isolation stress and inhibited protein biosynthesis on learning and memory in goldfish

Goldfish, Carassius auratus auratus L. (Pisces, Cyprinidae), were trained by different kinds of training procedures under the influence of cycloheximide or puromycin, two inhibitors of the protein biosynthesis. After active avoidance training in a shuttle box an apparent amnesia was found only when the fish were exposed to a one day lasting isolation stress prior to training. If the animals were accustomed to isolation over a period of 20 days the inhibitors did not affect memory formation. After learning by positive reinforcement (food rewarded color discrimination) in groups under stress-free conditions, neither learning nor memory formation were impaired in spite of the presence of cycloheximide. It is suggested that the amnestic effect of the inhibitors is caused by isolation treatment. Lack of the additional stress, however, leads to memory formation.     

Involvement of retrosplenial cortex in forming associations between multiple sensory stimuli

The retrosplenial cortex (RSP) is highly interconnected with medial temporal lobe structures, yet relatively little is known about its specific contributions to learning and memory. One possibility is that RSP is involved in forming associations between multiple sensory stimuli. Indeed, damage to RSP disrupts learning about spatial or contextual cues and also impairs learning about co-occurring conditioned stimuli (CSs). Two experiments were conducted to test this notion more rigorously. In Experiment 1, rats were trained in a serial feature negative discrimination task consisting of reinforced presentations of a tone alone and nonreinforced serial presentations of a light followed by the tone. Thus, in contrast to prior studies, this paradigm involved serial presentation of conditioned stimuli (CS), rather than simultaneous presentation. Rats with damage to RSP failed to acquire the discrimination, indicating that RSP is required for forming associations between sensory stimuli regardless of whether they occur serially or simultaneously. In Experiment 2, a sensory preconditioning task was used to determine if RSP was necessary for forming associations between stimuli even in the absence of reinforcement. During the first phase of this procedure, one auditory stimulus was paired with a light while a second auditory stimulus was presented alone. In the next phase of training, the same light was paired with food. During the final phase of the procedure both auditory stimuli were presented alone during a single session. Control, but not RSP-lesioned rats, exhibited more food cup behavior following presentation of the auditory cue that was previously paired with light compared with the unpaired auditory stimulus, indicating that a stimulus-stimulus association was formed during the first phase of training. These results support the idea that RSP has a fundamental role in forming associations between environmental stimuli.     

Aversive effects and retention impairment induced by acetoxycycloheximide in an instrumental task.

AXM, when subcutaneously injected during the first 3 min following the acquisition of a nondiscriminative instrumental learning task, induced an aversion for the food reinforcement which had been associated with the training situation and with the pharmacological treatment. The high number of nonreinforced responses preceding the first reinforced response(RR) that animals performed when tested 6 days after AXM treatment, was not due to forgetting of the lever significance, but to this aversion. Animals treated with AXM showed low levels of lever pressing response and long latencies for their first RR; this deficit did not seem only to be due to food reinforcement aversion; it disappeared, as well as food aversion, when food reinforcement which had been associated with the learning situation and to treatment, was added to the daily feeding regimen during treatment-test interval. It has been shown, moreover, that more than 90 percent of cerebral protein synthesis was inhibited during the 5 hr following subcutaneous AXM injection. These findings are interpreted as an indication that AXM does not affect memory consolidation of a non discriminative instrumental learning.     

Food restriction reconfigures naïve and learned choice behavior in Drosophila larvae

Abstract

In many animals, the establishment and expression of food-related memory is limited by the presence of food and promoted by its absence, implying that this behavior is driven by motivation. In the past, this has already been demonstrated in various insects including honeybees and adult Drosophila. For Drosophila larvae, which are characterized by an immense growth and the resulting need for constant food intake, however, knowledge is rather limited. Accordingly, we have analyzed whether starvation modulates larval memory formation or expression after appetitive classical olfactory conditioning, in which an odor is associated with a sugar reward. We show that odor-sugar memory of starved larvae lasts longer than in fed larvae, although the initial performance is comparable. 80 minutes after odor fructose conditioning, only starved but not fed larvae show a reliable odor-fructose memory. This is likely due to a specific increase in the stability of anesthesia-resistant memory (ARM). Furthermore, we observe that starved larvae, in contrast to fed ones, prefer sugars that offer a nutritional benefit in addition to their sweetness. Taken together our work shows that Drosophila larvae adjust the expression of learned and naïve choice behaviors in the absence of food. These effects are only short-lasting probably due to their lifestyle and their higher internal motivation to feed. In the future, the extensive use of established genetic tools will allow us to identify development-specific differences arising at the neuronal and molecular level.     

Phenotypic characterization of spatial cognition and social behavior in mice with 'knockout' of the schizophrenia risk gene neuregulin 1

Neuregulin-1 (NRG1) has been identified as a candidate susceptibility gene for schizophrenia. In the present study the functional role of the NRG1 gene, as it relates to cognitive and social processes known to be disrupted in schizophrenia, was assessed in mice with heterozygous deletion of transmembrane (TM)-domain NRG1 in comparison with wildtypes (WT). Social affiliative behavior was assessed using the sociability and preference for social novelty paradigm, in terms of time spent in: (i) a chamber containing an unfamiliar conspecific vs. an empty chamber (sociability), or (ii) a chamber containing an unfamiliar conspecific vs. a chamber containing a familiar conspecific (preference for social novelty). Social dominance and aggressive behavior were examined in the resident-intruder paradigm. Spatial learning and memory were assessed using the Barnes maze paradigm, while spatial working memory was measured using the continuous variant of the spontaneous alternation task. Barnes maze data revealed intact spatial learning in NRG1 mutants, with elevated baseline latency to enter the escape hole in male NRG1 mutants reflecting an increase in activity level. Similarly, although a greater number of overall arm entries were found, spontaneous alternation was unaffected in NRG1 mice. Social affiliation data revealed NRG1 mutants to evidence a specific loss of WT preference for spending time with an unfamiliar as opposed to a familiar conspecific. This suggests that NRG1 mutants show a selective impairment in response to social novelty. While spatial learning and working memory processes appear intact, heterozygous deletion of TM-domain NRG1 was associated with disruption to social novelty behavior. These data inform at a novel phenotypic level on the functional role of this gene in the context of its association with risk for schizophrenia.     

Complete maternal deprivation affects social, but not spatial, learning in adult rats

The effects of maternal deprivation on learning of social and spatial tasks were investigated in female adult rats. Pups were reared artificially and received "lickinglike" tactile stimulation (AR animals) or were reared with their mothers (MR animals). In adulthood, subjects were tested on paradigms of spatial learning and on paradigms involving learning of social cues. Results showed that maternal deprivation did not affect performance on spatial learning, but it did impair performance on the three social learning tasks. The AR animals made no distinction between a new and a previously presented juvenile conspecific. AR animals also responded less rapidly than MR animals at test for maternal behavior 2 weeks after a postpartum experience with pups. Finally, AR animals did not develop a preference for a food previously eaten by a familiar conspecific whereas MR animals did. This study indicates that animals reared without mother and siblings show no deficits in spatial tasks while showing consistent deficits in learning involving social interactions.     

Cognitive and neuronal systems underlying obesity

Since the late 1970s obesity prevalence and per capita food intake in the USA have increased dramatically. Understanding the mechanisms underlying the hyperphagia that drives obesity requires focus on the cognitive processes and neuronal systems controlling feeding that occurs in the absence of metabolic need (i.e., "non-homeostatic" intake). Given that a portion of the increased caloric intake per capita since the late 1970s is attributed to increased meal and snack frequency, and given the increased pervasiveness of environmental cues associated with energy dense, yet nutritionally depleted foods, there's a need to examine the mechanisms through which food-related cues stimulate excessive energy intake. Here, learning and memory principles and their underlying neuronal substrates are discussed with regard to stimulus-driven food intake and excessive energy consumption. Particular focus is given to the hippocampus, a brain structure that utilizes interoceptive cues relevant to energy status (e.g., neurohormonal signals such as leptin) to modulate stimulus-driven food procurement and consumption. This type of hippocampal-dependent modulatory control of feeding behavior is compromised by consumption of foods common to Western diets, including saturated fats and simple carbohydrates. The development of more effective treatments for obesity will benefit from a more complete understanding of the complex interaction between dietary, environmental, cognitive, and neurophysiological mechanisms contributing to excessive food intake.     

Learning about deprivation intensity stimuli

Rats demonstrated that they can use deprivation-produced stimuli as discriminative signals for shock in three experiments that used observation of freezing behavior as the index of learning. In Experiment 1, one group was shocked under 24-hr, but not under 0-hr food deprivation. Another group received the reversed discrimination. Both groups froze more under their shocked than under their nonshocked deprivation level. Furthermore, freezing was greatest under a given deprivation level for the group shocked under that level. Behavior was shown to be a function of this learning during subsequent testing under other deprivation levels. In Experiment 2, rats discriminated between deprivation intensities approximating those encountered under free-feeding conditions, and behavior under other deprivation levels also depended on this learning. Experiment 3, using 6- and 23-hr food deprivation, showed that discriminative responding occurred in the absence of cues arising from the recent memory of food in the home cage. Generalization of discriminative control to cues produced by intubation of a high calorie load and to injection of insulin (Experiment 3A) provided evidence that animals learned about the interoceptive stimulus consequences of their deprivation states. The results encourage the view that learning about internal stimulus aspects of food deprivation plays a role in appetitive behavior.     

Age-related changes in brain proDynorphin gene expression in the rat

Dynorphin has a well-established role in feeding and gustation. Alterations in taste perception and feeding behavior are common with age. We hypothesized that proDynorphin gene expression in brain areas involved in taste and feeding declines with age. Male Sprague-Dawley rats were housed individually with ad libitum access to food and water. Brain punches of the selected regions were dissected out in groups of rats aged 4–6, 12–14 and 18–21 months. ProDynorphin mRNA (measured using a cDNA probe) decreased significantly with age in arcuate nucleus and amygdala; increased significantly with age in hippocampus; and was not significantly affected in nucleus of the solitary tract, cortex, caudate putamen or hypothalamic paraventricular nucleus. These data suggest an age-related decrease in the synthesis of dynorphin in two brain regions strongly associated with feeding behavior, and an increase in dynorphin synthesis in a brain region associated with learning and memory.     

惊厥阈下脑放电对大鼠空间变换学习记忆的影响

目的：考查痫样放电对大鼠空间变换学习记忆影响。方法：在大鼠前额叶皮层给予引起痫样放电但无惊厥发作的阈下电刺激，建立惊厥阈下脑放电的动物模型。对大鼠进行空间变换学习记忆能力测定。结果：训练前给予阈下电刺激，可影响信息的获得，训练后给予阈下电刺激可影响短时记忆向长时记忆的转化。在已形成长时记忆时，阈下电刺激则干扰信息的提取。对刺激组停止刺激，动物的训练成绩逐日提高并在一周内达标。结论：阈下电刺激引起的认知损害是可逆的。     

Further study of the learning deficit produced by hydroxylamine

The albino mice were trained in alimentary conditioning, light associated with food pellet. Hydroxylamine injected intracranially from four hours to three weeks after the end of training series interfered with the retention of the learned task. Hydroxylamine injected four weeks after the end of training and later was ineffective. In the sixth and eighth week after the end of training, the forgetting appeared in all groups of animals. Retraining was possible in all groups. Learning of another task, one-trial learning situation, parallel with the testing series of sessions, was not affected by previous injection of hydroxylamine.     

Basal ganglia-dependent processes in recalling learned visual-motor adaptations

Humans learn and remember motor skills to permit adaptation to a changing environment. During adaptation, the brain develops new sensory–motor relationships that become stored in an internal model (IM) that may be retained for extended periods. How the brain learns new IMs and transforms them into long-term memory remains incompletely understood since prior work has mostly focused on the learning process. A current model suggests that basal ganglia, cerebellum, and their neocortical targets actively participate in forming new IMs but that a cerebellar cortical network would mediate automatization. However, a recent study (Marinelli et al. 2009) reported that patients with Parkinson’s disease (PD), who have basal ganglia dysfunction, had similar adaptation rates as controls but demonstrated no savings at recall tests (24 and 48 h). Here, we assessed whether a longer training session, a feature known to increase long-term retention of IM in healthy individuals, could allow PD patients to demonstrate savings. We recruited PD patients and age-matched healthy adults and used a visual-motor adaptation paradigm similar to the study by Marinelli et al. (2009), doubling the number of training trials and assessed recall after a short and a 24-h delay. We hypothesized that a longer training session would allow PD patients to develop an enhanced representation of the IM as demonstrated by savings at the recall tests. Our results showed that PD patients had similar adaptation rates as controls but did not demonstrate savings at both recall tests. We interpret these results as evidence that fronto-striatal networks have involvement in the early to late phase of motor memory formation, but not during initial learning.