The procerebrum is necessary for odor-aversion learning in the terrestrial slug Limax valentianus

The terrestrial slug Limax has a highly developed ability to associate the odor of some foods (e.g., carrot juice) with aversive stimuli such as the bitter taste of quinidine solution. The procerebrum (PC) is a part of the slug's brain thought to be involved in odor-aversion learning, but direct evidence is still lacking. Here we present evidence showing that the PC is essential for odor-aversion learning. Unlike sham-operated slugs, PC ablation 7 d prior to conditioning showed that most slugs did not avoid carrot juice in the memory retention test conducted 24 h after the conditioning. Slugs with the PC ablated 3 h, 1 d, 3 d, or 7 d after conditioning and examined by the memory retention test at 3 d after the PC ablation were also less likely to avoid carrot juice than sham-operated slugs. The PC ablation did not damage the ability of the slugs to sense attractive odor (everyday food) or innately aversive odor (onion or garlic). These results demonstrate that the PC is a necessary component in the retention and/or retrieval of odor-aversion memory.     

A neuropsychological study of fact memory and source amnesia

We investigated the ability of amnesic patients to learn new facts (e.g., Angel Falls is located in Venezuela) and also to remember where and when the facts were learned (i.e., source memory). To assess the susceptibility of fact and source memory to retrograde amnesia, patients prescribed electroconvulsive therapy were presented facts prior to the first treatment and were tested after their second treatment. All amnesic patients exhibited marked fact memory impairment. In addition, some amnesic patients exhibited source amnesia (i.e., they recalled a few facts but then could not remember where or when those facts had been learned). Source amnesia was unrelated to the severity of the memory deficit itself, because patients who exhibited source amnesia recalled as many facts as the patients who did not. These results show that the deficit in amnesia includes an impairment in acquiring and retaining new facts. Source amnesia can also occur, but it is dissociable from impaired recall and recognition and appears to reflect difficulty in remembering the specific context in which information is acquired. The findings are discussed in terms of their significance for how memory is organized.     

Learning during the newborn's first meal: special resistance to retroactive interference

At their first postnatal meal, 3-hour-old rats learned an association between an odor and a sweet or bitter taste. Retention after a long interval or after associative interference was compared to that of 1-day-old rats. Despite equivalent and negligible effect of the long retention interval, contrary to infantile amnesia, newborns differed strikingly from 1-day-olds in susceptibility to associative interference. When lemon odor predicted saccharin in the first episode but quinine in the second, 1-day-olds had strong retroactive interference, but the newborn's first memory was unaffected by the second. The results were identical when the first memory was a lemon-quinine association and the second a lemon-saccharin association. It is uncertain whether this special robustness of memories associated with the first postnatal meal is best understood in terms of cognitive primacy or neurochemical and physiological consequences of the birth process.     

Transfer of newly acquired stimulus valence between identities in dissociative identity disorder (DID)

Patients with Dissociative Identity Disorder (DID) frequently report episodes of interidentity amnesia, that is amnesia for events experienced by other identities. The goal of the present experiment was to test the implicit transfer of trauma-related information between identities in DID. We hypothesized that whereas declarative information may transfer from one identity to another, the emotional connotation of the memory may be dissociated, especially in the case of negative, trauma-related emotional valence. An evaluative conditioning procedure was combined with an affective priming procedure, both performed by different identities. In the evaluative conditioning procedure, previously neutral stimuli come to refer to a negative or positive connotation. The affective priming procedure was used to test the transfer of this acquired valence to an identity reporting interidentity amnesia. Results indicated activation of stimulus valence in the affective priming task, that is transfer of emotional material between identities.     

Temporally graded,context-specific retrograde amnesia and its alleviation by context preexposure: effects of postconditioning exposures to morphine in the rat

Five experiments studied retrograde impairments in Pavlovian fear conditioning following prolonged exposure to the opioid receptor agonist morphine. Injections of morphine commencing 1-7 days but not 14 days after conditioning produced amnesia for that conditioning episode. This amnesia was (a) selective such that morphine impaired freezing to the conditioning context but not to the auditory conditioned stimulus, (b) independent of the interval between the last injection of morphine and test, and (c) accompanied by a failure of contextual discrimination. Context preexposure protected context conditioning and discrimination from the amnestic effects of morphine. These results show that retrograde deficits in contextual fear conditioning are mediated by failures to consolidate a contextual representation.     

Stability of long temporal gradients of retrograde amnesia in mice

Mice were given a single training trial and then received a series of four electroconvulsive shocks (ECS), 1 h apart, at one of several times after training (1-180 days). Retention was then tested at one of three times after ECS: 7, 14, or 28 days. Control animals that received sham treatment exhibited gradual forgetting with increasing training-retention intervals. Mice given ECS exhibited temporally graded retrograde amnesia, which affected memories acquired up to about 14 days before treatment. The retrograde amnesia was relatively stable, maintaining its temporally graded appearance for at least 28 days after ECS. Some recovery may have occurred in the case of memories acquired 7 days or longer before ECS, but memories acquired only 1 or 5 days before ECS did not recover. These findings extend the parallel between experimental amnesia in laboratory animals and human amnesia.     

The memory‐impairing effects of simulated amnesia for a mock crime

The present study examined whether mock offenders, who were instructed to falsely deny crime details or to simulate amnesia, would consequently experience impaired memory. Ninety‐three university students were first asked to commit a mock crime and were then assigned to three different conditions (i.e., false denial, simulated amnesia, and truth telling) and then received the first memory test. The following day, participants completed a second memory test. Results showed that the memory impairment was not observed in participants in the false denial condition. However, in the simulated amnesia group, memory about being interviewed in the first session was impaired. The simulated amnesia group also had lower recollection and belief ratings in the occurrence of true details for the mock event. Findings suggest that after simulating amnesia, offenders can forget details related to the interview and exhibit diminished ratings for the recollection of and belief in their memory for experienced events.     

Muscimol Induces Retrograde Amnesia for Changes in Reward Magnitude

These experiments examined the effect of the GABA_A, agonist, muscimol (MUS), on memory for changes in reward magnitude. In Experiment 1 rats were trained to run a straight alley for either a large or small food reward. After reaching asymptotic performance rats in the high reward group were shifted to the small food reward. Half the animals received 1.0 or 3.0 mg/kg (ip) of MUS or the equivalent volume of saline immediately after training. Shifted training continued for 3 more days and no further injections were given. Shifted saline animals displayed an increase in response latencies compared to unshifted controls with a sharp peak on the day after the shift. Shifted MUS receiving 1.0 mg/kg performed comparably to shifted saline animals. In contrast, shifted MUS animals receiving 3.0 mg/kg displayed performance comparable to shifted saline animals on the day of the shift but displayed a sharp increase in response latencies on the second day after the shift. These findings indicate that post-training systemic MUS injections delay the peak increase in response latencies and suggest that MUS induces retrograde amnesia for reward reduction. Experiment 2 examined the effect of MUS on the memory of a reward increase. Rats were first trained as in Experiment 1 and rats under the high reward condition were then shifted to the small reward. On the next training session, the large food reward was reinstated. Immediately after the session all animals were injected with saline or 3.0 mg/kg of MUS. The large food reward was continued for the remainder of training and no further injections were given. On the following session, the performance of the shifted saline animals was comparable to that of the unshifted controls while shifted MUS animals displayed significantly higher response latencies. The findings that MUS prevented the reduction in response latencies seen in saline-injected animals suggest that MUS also induces retrograde amnesia for reward increases.     

Functional amnesia: clinical description and neuropsychological profile of 10 cases

We carried out the first neuropsychological study of a series of patients with functional amnesia. We evaluated 10 patients, first with a neurological examination and then with three tests of anterograde amnesia and four tests of retrograde amnesia. Excluding one patient who later admitted to malingering, all patients had a significant premorbid psychiatric history and one or more possible precipitating factors for their amnesia. Eight of the 10 patients still had persistent retrograde amnesia at our last contact with them (median = 14 mo after the onset of amnesia). On tests of anterograde amnesia, the patients performed normally as a group, though some patients scored poorly on tests of verbal memory. On tests of retrograde amnesia, all patients had difficulty re-collecting well-formed autobiographical memories of specific events from their past. In contrast, patients performed as well as controls at distinguishing the names of cities from fictitious city names. On remote memory tests for past public events and famous faces, different patients exhibited different but internally consistent patterns of impaired and spared performance. The variability in the clinical and neuropsychological findings among our patients may be understood by supposing that memory performance is poor in proportion to how directly a test appears to assess a patient's common sense concept of memory. The presentation of patients with functional amnesia is as variable as humankind's concept of what memory is and how it works.     

Somatic and autonomic indexes of recovery from electroconvulsive shock-induced amnesia in rats

Autonomic response indexes of experimental amnesia have recently been found to have higher electroconvulsive shock (ECS) intensity thresholds and steeper retrograde gradients than have traditional somatic indexes. The present studies examined the hypothesis that recovery from somatically indexed experimental amnesia depends upon the existence of autonomically available residual memory. In a between-subjects design, a 200-mA ECS was used to produce amnesia for a tone-footshock pairing as indicated by lick suppression, defection, and bradycardia. The next day, these amnesic animals received a reminder footshock outside of the training apparatus, which was found to restore memory on a test trial 24 hr later. The behavior of control groups indicated that this reminder effect was due to the restoration of specific memory rather than systemic consequences of treatment. With a within-subjects design, a second experiment obtained a reminder effect in animals individually shown to be "fully" amnesic by all three response indexes monitored. A third experiment varied the intensity of the reminder footshock and revealed that the different memory indexes examined do not have reminder-footshock thresholds inversely related to their initial resistance to amnesia. The results support a retrieval-failure view of experimental amnesia and suggest that the same fundamental physiological processes underlie both autonomically indexed memory and somatically indexed memory.     

Anterograde and retrograde amnesia of place discrimination in retrosplenial cortex and hippocampal lesioned rats

Retrograde and anterograde amnesic effects of excitotoxic lesions of the rat retrosplenial cortex (RS) and hippocampus (HPC) were investigated. To test retrograde amnesia, rats were trained with two-arm place discrimination in a radial maze 4 wk and 1 d before surgery with a different arm pair, respectively. In the retention test 1 wk after surgery, both lesion groups showed temporally ungraded retrograde amnesia. To test anterograde amnesia, animals were trained after surgery to discriminate three arm pairs successively within a day, and then after interposition of 1- to 4-wk intervals, one of these pairs, respectively, was tested for retention. RS-lesioned rats could acquire these pairs of place discriminations rapidly but showed a retention interval-dependent impairment in the retention test. Conversely, HPC-lesioned rats took more sessions to acquire these pairs than did the control group, and their retention was approximately 70% of correct performance regardless of retention interval. Results suggest that RS and HPC have different roles in spatial memory and that RS is important for remote memory process.     

Toilet rooms, body massages, and smells: Two field studies on human evaluative odor conditioning

In two experimental field studies, the hypothesis was tested that Pavlovian conditioning may modify adults’ liking or disliking of an odor. In Experiment 1, an odor (CS) was first paired unobtrusively with toilet stimuli (US). Next, Ss rated the experimental and a control odor on Semantic Differential items. For Ss evaluating going-to-the-toilet negatively, an acquired dislike for the toilet-paired odor relative to a nonexposed control odor was observed, whereas in Ss evaluating going-to-the-toilet positively, the reverse was observed. In Experiment 2, a neutral odor (CS) was mixed into the massage oil with which a physiotherapist treated his patients. Half of the Ss were treated with Positive-relaxing massage, half of the Ss with Negative-painful massage. At the medical follow-up, Semantic Differential ratings were obtained both for the treatment-odor and for a control odor. In the Positive massage group, the treatment odor was rated as more positive and as less dynamic than the control odor. No similar effects were observed in the Negative massage group, a failure which was probably due to the intended Negative massage not really being experienced as a disliked event. In both experiments, an almost identical pattern of results was observed in the subgroup of Ss who didnot consciously recognize the experimental odor as the treatment odor, eliminating the possibility that the results should be due to demand. As mere exposure cannot account for the results, they most probably represent genuine instances of evaluative odor conditioning. The results are discussed in terms of the understanding of the origins of the affective meaning of odorants, and are related to human evaluative conditioning and implicit memory issues.     

Late expression of brain-derived neurotrophic factor in the amygdala is required for persistence of fear memory

In many instances, increase in neuronal activity can induce biphasic secretion of a modulator. The initial release of the modulator triggers the induction of synaptic plasticity, whereas the second-phase release reinforces the efficacy of synaptic transmission and growth of dendrites and axons. In this study, we showed that fear conditioning not only induced the first but also a second peak of brain-derived neurotrophic factor (BDNF) expression. Fluorescent immunohistostaining confirmed that BDNF expression increased at 1 and 12 h after conditioning and returned to baseline at 30 h after conditioning. Mature BDNF expression increased in a similar manner. TrkB-IgG or K252a infusion before training impaired fear memory on days 1 and 7 after training. In contrast, TrkB-IgG or K252a infusion 9 h after fear conditioning did not affect memory retention on day 1 after training but impaired fear memory on day 7 after training. Fear conditioning significantly enhanced Zif268 expression in the amygdala at 12 h after training; this enhanced expression was completely inhibited by TrkB-IgG infusion 9 h after training. The level of growth-associated protein 43 (GAP-43), a marker of newly formed synapses, in the amygdala increased 7 days after fear conditioning. Moreover, conditioned rats had higher AMPA/NMDA ratio than unpaired rats. These results suggest that consolidated memory could be continuously modulated by previous molecular changes produced during memory acquisition.     

Role of verbal encoding in shortand long-term odor recognition

The role of verbal encoding in odor recognition memory was investigated using odors of low familiarity to subjects before the experiment began. The experimental procedure included two phases—odor learning (first phase) and odor memory testing (second phase)—separated by a delay of 7 days. Five experimental conditions were established: three conditions of odor learning with names (labeling conditions), one condition of odor learning without names (sensory familiarization), and one condition of no learning prior to testing (control conditions). The labeling conditions differed from each other regarding label characteristics. The names were those of odor sources (veridical names), those personally generated by subjects (generated names), or those derived from the chemical names of the odorants (chemical names). Subjects were required to learn 20 fixed associations between odors (targets or distractors) and 20 names during two daily sessions. The learning sessions included two identification tests and ended by a verbal memory test in which subjects recalled odor names. The odor memory test was split into two parts separated by a retention interval of either 20 min (short-term memory) or 24 h (long-term memory). Data showed that olfactory recognition memory was enhanced in subjects who associated veridical or generated names to odors during the learning session. Chemical names were not appropriate to facilitate odor recognition. Similarly, the level of odor identification was higher for veridical and generated names than for chemical names, though the level of verbal memory for chemical names was substantial. Recognition response latencies were systematically longer for a target odor implying a positive response than for a distractor odor implying a negative response. Together, these data suggest that odor recognition and identification are sensitive to the semantic content of labels associated with odors. Odor memory was adversively influenced by time, but this influence was less pronounced when the names were endowed with a rich semantic content.     

Affective priming as an indirect measure of food preferences acquired through odor conditioning

The present study aimed at investigating affective priming for originally neutral food stimuli that recently acquired their affective meaning through odor conditioning. In a first phase, pictures of different brands of yogurts (CSs) were contingently presented with a positive or negative odor (US). In a subsequent phase, the yogurt CSs were used as primes in an affective priming procedure. Rating data showed that the acquisition procedure resulted in a reliable evaluative learning effect. This could be corroborated by the results of the priming task. Participants responded faster to positive target words and made fewer errors when they were preceded by a CS that had been associated with a positive odor, as compared to a CS that was associated with a negative odor. A reversed pattern was present for negative targets. Based on these findings, it is suggested that affective priming might be used as a demand-free measure of evaluative learning.     

Scopolamine Selectively Disrupts the Acquisition of Contextual Fear Conditioning in Rats

Muscarinic cholinergic antagonism produces learning and memory deficits in a variety of hippocampal-dependent tasks. Hippocampal lesions produce both acquisition deficits and retrograde amnesia for contextual fear conditioning, but do not impact fear conditioning to discrete cues. In order to examine the effects of muscarinic antagonism in this paradigm, rats were given scopolamine (1 mg/kg) either before or for 3 days after a Pavlovian fear-conditioning session in which tones were paired with aversive footshocks. Fear to the context and the tone was assessed by measuring freezing in separate tests. It was found that pretraining, but not posttraining, scopolamine severely impaired contextual fear conditioning; tone conditioning was not affected under either condition (cf., Young, Bohenek, & Fanselow,Neurobiology of Learning and Memory,63,174–180, 1995).     

Differential Effects of Ketaset/Rompun Anesthesia on Hypothermia-Induced Retrograde Amnesia and Its Recovery

A nonbarbiturate anesthetic consisting of ketamine HCl (Ketaset) and xlyazine (Rompun) was administered to assess the effects of anesthesia on hypothermia-induced retrograde amnesia in Long Evans hooded and Sprague–Dawley albino rats. Results from Experiment 1a indicate that this anesthetic does not attenuate retrograde amnesia, and the findings from Experiment 1b suggest that awakening from Ketaset/Rompun anesthesia at normal body temperature (following administration of deep body cooling) does not attenuate the resulting hypothermia-induced retrograde amnesia. Experiment 2 demonstrated that various delays between training and hypothermia resulted in a temporal gradient that was the same for animals cooled while either conscious or under anesthesia. The results of Experiment 3 showed that rats made amnesic while under anesthesia did not recover the target memory if given a recooling treatment, but rats that were made amnesic while conscious did recover the memory with the same reminder treatment. These findings indicate that the conscious processing of stimuli associated with hypothermia treatment is not necessary in inducing hypothermia-induced retrograde amnesia, but that conscious processing is an important factor if the amnesia is to be recovered with a recooling treatment.     

Simultaneous odor-taste and taste-taste compounds in poison-avoidance learning

In six experiments, rats received an odor or a taste alone or in simultaneous compound with another taste prior to lithium chloride-induced illness. Aversions to the target odor and the target taste were then assessed. In Experiments 1–3, the presence of the taste in compound with the target during conditioning attenuated the strength of the aversions to both the target odor and the target taste. Although these results were consistent with the familiar principles of compound conditioning, they contradicted previous reports of potentiation, rather than attenuation, of odor conditioning by taste. In Experiment 4, taste again attenuated the conditioning of odor when a second odor was presented during the CS-US interval. In Experiment 5, we looked for odor potentiation with a within-subject design, and in Experiment 6, we examined an alternative method of presenting odor. In neither case did we find odor potentiation by taste. Over the range of conditions investigated here, a taste often attenuates, and never potentiates, the conditioning of aversions to both odors and tastes.     

Growth points in research on memory and hippocampus.

We present an overview of two of our on-going projects relating processes in the hippocampus to memory. We are trying to understand why retrograde amnesia occurs after damage to the hippocampus. Our experiments establish the generality of several new retrograde amnesia phenomena that are at odds with the consensus view of the role of the hippocampus in memory. We show in many memory tasks that complete damage to the hippocampus produces retrograde amnesia that is equivalent for recent and remote memories. Retrograde amnesia affects a much wider range of memory tasks than anterograde amnesia. Normal hippocampal processes can interfere with retention of a long-term memory stored outside the hippocampus. We conclude that the hippocampus competes with nonhippocampal systems during memory encoding and retrieval. Finally, we outline a project to understand and manipulate adult hippocampal neurogenesis in order to repair damaged hippocampal circuitry to recover lost cognitive functions.     

Impaired memory consolidation in rats produced with beta-adrenergic blockade

Despite abundant evidence that systemic administration of adrenergic drugs and hormones can produce retrograde memory enhancement, the literature contains no clear demonstration that postlearning systemic administration of adrenergic antagonists produces retrograde amnesia. Here we demonstrate retrograde amnesia for a stressful learning task (a spatial water maze) with systemic administration of the beta-adrenergic antagonist propranolol (5 mg/kg). The amnesic effect of the drug depended on the degree of learning in the subjects: Propranolol caused a robust retrograde amnesia in "good learners," but did not significantly affect memory in "poor learners." The findings provide critical additional support for the hypothesis that postlearning adrenergic activation modulates memory consolidation processes after emotionally stressful events and help explain previous failures to detect memory impairment after systemic administration of adrenergic blocking drugs.