Behavioral and genetic characterization of habituation using Caenorhabditis elegans

This review surveys the literature that investigates the behavioral characterization and cellular and molecular mechanisms of habituation using the model organism Caenorhabditis elegans. In 1990, C. elegans was first observed to show habituation to a non-localized mechanical tap. The parameters that govern this behavioral plasticity in C. elegans were subsequently characterized, which lead to the important hypothesis that habituation is mediated by multiple mechanisms. Many tools are available to C. elegans researchers that allow for relatively easy genetic manipulation. This has lead to a number of recent genetic studies that have begun to identify key genes and molecules that play a role in the mechanisms of habituation. Some of these genes include a vesicular glutamate transporter, a glutamate receptor subunit, a dopamine receptor and downstream intracellular signaling molecules, such as G proteins and kinases. Some of these genes only affect certain parameters of habituation, but not others supporting the hypothesis that multiple mechanisms mediate habituation. The field of research has also led to the dissection of different phases of memory (short-term vs. long-term memory for habituation), which are triggered by different training paradigms. The differences in mechanism between these various forms of memory are also beginning to be revealed.     

Low environmental calcium blocks long-term memory formation in a freshwater pulmonate snail

The freshwater snail Lymnaea stagnalis (L.) is considered a calciphile and exhibits reduced growth and survival in environments containing less than 20 mg/l environmental calcium. Although it has no apparent effect on survival at 20 mg/l, reducing environmental calcium increases metabolic demand, and as such we consider that this level of calcium acts as a stressor on the snail. We exposed snails to acute periods of low environmental calcium and tested their ability to form intermediate-term memory (ITM) and long-term memory (LTM) following one trial operant conditioning (1TT) to reduce aerial respiratory activity in hypoxic conditions. We also assessed whether there were changes in the electrophysiological properties of a single neuron, right pedal dorsal 1 (RPeD1), which has been demonstrated to be necessary for LTM formation. Following training in high (80 mg/l) environmental calcium, L. stagnalis formed ITM and LTM lasting 24 h and demonstrated a significant reduction in all activity measured from RPeD1; however when snails were exposed to low (20 mg/l) environmental calcium they were able to form ITM but not LTM. Although no behavioral LTM was formed, a partial reduction in RPeD1 activtiy measured 24 h after training was observed, indicating a residual effect of training. The strong effect that environmental calcium concentration had on physiology and behavior in response to training to reduce aerial respiration in L. stagnalis suggests that it is an element of gastropod husbandry that needs to be carefully considered when studying other traits. This study also indicates that L. stagnalis found naturally in low calcium environments may be less able to adapt to novel stressors than populations found in harder waters.     

Multiple memory stores and operant conditioning: a rationale for memory's complexity

Why does the brain contain more than one memory system? Genetic algorithms can play a role in elucidating this question. Here, model animals were constructed containing a dorsal striatal layer that controlled actions, and a ventral striatal layer that controlled a dopaminergic learning signal. Both layers could gain access to three modeled memory stores, but such access was penalized as energy expenditure. Model animals were then selected on their fitness in simulated operant conditioning tasks. Results suggest that having access to multiple memory stores and their representations is important in learning to regulate dopamine release, as well as in contextual discrimination. For simple operant conditioning, as well as stimulus discrimination, hippocampal compound representations turned out to suffice, a counterintuitive result given findings that hippocampal lesions tend not to affect performance in such tasks. We argue that there is in fact evidence to support a role for compound representations and the hippocampus in even the simplest conditioning tasks.     

Hippocampal c-fos is necessary for long-term memory of a socially transmitted food preference

The present article examined the requirement of hippocampal c-Fos for learning a socially transmitted food preference (STFP). We reported previously that expression of the c-Fos protein is increased in the dorsal and ventral hippocampus of rats trained on the STFP (Countryman, Orlowski, Brightwell, Oskowitz, & Colombo, 2005). Pretraining intrahippocampal antisense to the immediate early gene c-fos was administered to adult male Long-Evans rats to determine if c-fos expression is necessary for either short- or long-term memory for STFP. Guide cannulae were implanted bilaterally into the dorsal hippocampus. Antisense oligodeoxynucleotides (ODNs) were administered unilaterally either 6.5, 8.5, 10.5, or 12.5 h prior to STFP training while either sense ODNs or saline were infused into the opposite hemisphere. Immunocytochemistry was performed, and cells showing c-Fos immunoreactivity (ir) were counted from the antisense-treated hemisphere and compared to cell counts from the control hemisphere. The results indicated significant suppression of learning-induced c-Fos protein at the 8.5 and 10.5 infusion-train intervals. Additional rats were implanted with cannulae into the dorsal and ventral hippocampus, and antisense ODNs, sense ODNs, or saline were administered bilaterally 8.5h prior to training. Rats were tested immediately and 14 days after training. Rats in all groups showed a significant preference for the demonstrated food at the short-term memory test. At the long-term memory test, however, rats infused with c-fos antisense showed no preference for the demonstrated food whereas rats infused with either sense or saline maintained their preference. The present findings suggest that c-fos is necessary for consolidation of non-spatial hippocampal-dependent memory.     

Working memory retrieval differences between medial temporal lobe epilepsy patients and controls: A three memory layer approach

Multi-store models of working memory (WM) have given way to more dynamic approaches that conceive WM as an activated subset of long-term memory (LTM). The resulting framework considers that memory representations are governed by a hierarchy of accessibility. The activated part of LTM holds representations in a heightened state of activation, some of which can reach a state of immediate accessibility according to task demands. Recent neuroimaging studies have studied the neural basis of retrieval information with different states of accessibility. It was found that the medial temporal lobe (MTL) was involved in retrieving information within immediate access store and outside this privileged zone. In the current study we further explored the contribution of MTL to WM retrieval by analyzing the consequences of MTL damage to this process considering the state of accessibility of memory representations. The performance of a group of epilepsy patients with left hippocampal sclerosis in a 12-item recognition task was compared with that of a healthy control group. We adopted an embedded model of WM that distinguishes three components: the activated LTM, the region of direct access, and a single-item focus of attention. Groups did not differ when retrieving information from single-item focus, but patients were less accurate retrieving information outside focal attention, either items from LTM or items expected to be in the WM range. Analyses focused on items held in the direct access buffer showed that consequences of MTL damage were modulated by the level of accessibility of memory representations, producing a reduced capacity.     

Global processing speed as a mediator of developmental changes in children's auditory memory span

This study examined the role of global processing speed in mediating age increases in auditory memory span in 5- to 13-year-olds. Children were tested on measures of memory span, processing speed, single-word speech rate, phonological sensitivity, and vocabulary. Structural equation modeling supported a model in which age-associated increases in processing speed predicted the availability of long-term memory phonological representations for redintegration processes. The availability of long-term phonological representations, in turn, explained variance in memory span. Maximum speech rate did not predict independent variance in memory span.     

But I thought it was Mickey Mouse: the effects of new postevent information on 18-month-olds' memory

Two experiments examined the effects of postevent information on 18-month-olds' event memory. Experiment 1 (N=60) explored whether children's memory was reinstated when action information was eliminated from the reinstatement and only object information was introduced. Experiment 2 (N=48) examined children's recall when either (a). information about the objects' target actions was replaced with new action information or (b). the original training objects were replaced with new objects. In an elicited-imitation paradigm, children were trained to perform six target actions, watched a video reinstatement 10 weeks later, and were tested for recall 24 h after reinstatement. Two results were found. First, a video reminder eliminating action information reinstated children's memory as effectively as a video containing object and action information. Second, children were reminded of their past training when during reinstatement action information was preserved and new objects were presented but were not reminded when object information was preserved and new actions were presented.     

Conceptual implicit memory and environmental context

Changes in environmental context between encoding and retrieval often affect explicit memory but research on implicit memory is equivocal. One proposal is that conceptual but not perceptual priming is influenced by context manipulations. However, findings with conceptual priming may be compromised by explicit contamination. The present study examined the effects of environmental context on conceptual explicit (category-cued recall) and implicit memory (category production). Explicit recall was reduced by context change. The implicit test results depended on test awareness (assessed with a post-test questionnaire). Among test-unaware participants, priming was equivalent for same-context and different-context groups, whereas for the test-aware, the same-context group produced more priming. Thus, when explicit contamination is controlled, changes in environmental context do not impair conceptual priming. Context dependency appears to be a general difference between implicit and explicit memory rather than a difference between conceptual and perceptual implicit memory. Finally, measures of mood indicated no changes in affect across contexts, arguing against mood mediation for the context effects in explicit recall.     

Differential memory-preserving effects of reminders at 6 months

Although reactivation and reinstatement reminders differ procedurally, differences in their memory-preserving effects have been described as artifactual. In three experiments, we examined this conclusion. One hundred and twelve 6-month-olds learned an operant task, forgot it, received a reactivation or reinstatement reminder to recover the inactive memory, and were tested after increasing delays until they forgot it again. In Experiments 1a and 1b, a single reactivation reminder extended infants' memory of an operant mobile task for 2 weeks after reminding, but a single reinstatement extended it for 4 weeks, when testing was discontinued. In Experiment 2, a single reinstatement extended 6-month-olds' memory of an operant train task for 19 weeks after reminding, when infants were almost 1 year old. After reactivation, infants remember this task for only 2 weeks. The finding that the memory-preserving effect of reinstatement is greater by an order of magnitude suggests that procedural differences between the two reminders have functional significance.     

Apodemus sylvaticus (LOXT) is a suitable mouse strain for testing spatial memory retention in the Morris water maze

Information on the difference in cognitive function between laboratory and wild-caught mice is anecdotal and this question has not been systematically studied. Moreover, studying a wild-caught mouse strain per se may add information to the repertoire of mouse strains available. We aimed to study spatial memory in a wild mouse strain (Apodemus sylvaticus, AS) as compared to two individual laboratory mouse strains.Male AS (n = 20), CD1 (n = 19) and C57BL/6J mice (n = 19), 12–14 weeks old, were used in the experiments. The Morris water maze (MWM) was used for determination of spatial memory and time spent in the target quadrant at time points 5 (D5) and 12 days (D12) was evaluated. During the acquisition phase latency to reach the platform and path length to reach the platform was evaluated.Following four training days on day 5 (D5), time spent in the target quadrant was highest in AS > CD1 > C57BL/6J (P < 0.006). On day 12 (D12), time spent in the target quadrant was significantly higher in AS than in both other strains (P < 0.001).All animals learned the task and during the acquisition phase, latency to reach the platform as well as path length decreased significantly in AS.It is concluded that the AS is the most suitable strain for the evaluation of spatial memory in the MWM and is presenting with memory retention superior to laboratory mouse strains CD1 and C57BL/6J.     

Variations in working memory capacity predict individual differences in general learning abilities among genetically diverse mice

Up to 50% of an individuals' performance across a wide variety of distinct cognitive tests can be accounted for by a single factor (i.e., "general intelligence"). Despite its ubiquity, the processes or mechanisms regulating this factor are a matter of considerable debate. Although it has been hypothesized that working memory may impact cognitive performance across various domains, tests have been inconclusive due to the difficulty in isolating working memory from its overlapping operations, such as verbal ability. We address this problem using genetically diverse mice, which exhibit a trait analogous to general intelligence. The general cognitive abilities of CD-1 mice were found to covary with individuals' working memory capacity, but not with variations in long-term retention. These results provide evidence that independent of verbal abilities, variations in working memory are associated with general cognitive abilities, and further, suggest a conservation across species of mechanisms and/or processes that regulate cognitive abilities.     

Developmental study of multiple memory stages in the cuttlefish, Sepia officinalis

The inhibition of predatory behavior observed during the "prawn-in-the-tube" procedure has been extensively used in studies of cuttlefish learning. The present study examines the effect of age on the conditioning of this response in the cuttlefish, Sepia officinalis. Data show that a significant increase in acquisition performance occurs between 15 and 21 days of age. The retention curves in 8- and 15-day-old cuttlefish show a monotonic memory process, presumably reflecting the presence of only short-term memory. In 21-day-old cuttlefish, there are two distinct processes which could be a labile short-term memory, and a subsequent intermediate memory. These mnesic systems seem to become more effective over the course of post-embryonic development. Moreover, the retention curves obtained in the oldest cuttlefish (30- and 90-day-old) bear a close resemblance to that observed in adults. These behavioral findings will allow further work on the cellular and molecular mechanisms of learning and memory in the cuttlefish.     

Musical and verbal memory in Alzheimer’s disease: A study of long-term and short-term memory

Musical memory was tested in Alzheimer patients and in healthy older adults using long-term and short-term memory tasks. Long-term memory (LTM) was tested with a recognition procedure using unfamiliar melodies. Short-term memory (STM) was evaluated with same/different judgment tasks on short series of notes. Musical memory was compared to verbal memory using a task that used pseudowords (LTM) or syllables (STM). Results indicated impaired musical memory in AD patients relative to healthy controls. The deficit was found for both long-term and short-term memory. Furthermore, it was of the same magnitude for both musical and verbal domains whether tested with short-term or long-term memory tasks. No correlation was found between musical and verbal LTM. However, there was a significant correlation between verbal and musical STM in AD participants and healthy older adults, which suggests that the two domains may share common mechanisms.     

Reactivated memory of an inhibitory avoidance response in mice is sensitive to a nitric oxide synthase inhibitor

It is accepted that once consolidation is completed memory becomes permanent. However, it has also been suggested that reactivation (retrieval) of the original memory, again, makes it sensitive to the same treatments that affect memory consolidation when given after training. Previous results demonstrated that the immediate post-training intraperitoneal administration of N^ω-nitro-l-arginine methyl ester (L-NAME), a non-specific inhibitor of nitric oxide synthase (NOS), impairs retention test performance of a one-trial step-through inhibitory avoidance response in adult mice. The effect of L-NAME on retention was attributed to an action on memory consolidation of the original learning. For the first time, we report that the administration of L-NAME after the first retention test (memory reactivation) of the inhibitory avoidance response impairs retention performance over six consecutive days. This impairment effect is dose-and-time dependent and could not be attributed to a retrieval deficit since a mild footshock did not reinstate the original avoidance response and no spontaneous recovery was observed at least 21 days after training. Further support for a storage deficit interpretation as opposed to a retrieval deficit was obtained from the fact that L-NAME’s effects after retrieval were not due to state-dependency. The impairment effect of L-NAME was dependent on the age of the original memory. That is, there was an inverse correlation between the susceptibility of the memory trace when reactivated and the time elapsed between training and the first retrieval session. We suggest an action of L-NAME on memory reactivation-induced processes that are different from memory extinction of the original learning extending the biological significance of nitric oxide on memory.     

Training and transfer effects of long-term memory retrieval training

ABSTRACT

Long-term memory retrieval ability and working memory can share attention control ability. Based on cognitive plasticity, a hypothesis that cognitive training could improve long-term memory retrieval efficiency and that this could transfer to retrieval involving working memory was proposed. 60 undergraduates were randomly assigned to a group of training and an active control group; all the participants completed the same tasks in the same order before and after the training, the tasks included a long-term memory retrieval access task, a intelligence test, a switching task, a working memory updating task, a response inhibition task and an interference control task. The statistics results indicate that cognitive training can improve long-term memory retrieval efficiency and has a transfer effect on working memory updating, interference control and switching ability, but not on response inhibition or intelligence. This reveal the plasticity of long-term memory retrieval and its influence on working memory.