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Mechanisms of same/different abstract-concept learning by rhesus monkeys (Macaca mulatta).

Experiments with 9 rhesus monkeys (Macaca mulatta) showed, for the first time, that abstract-concept learning varied with the training stimulus set size. In a same/different task, monkeys required to touch a top picture before choosing a bottom picture (same) or white rectangle (different) learned rapidly. Monkeys not required to touch the top picture or presented with the top picture for a fixed time learned slowly or not at all. No abstract-concept learning occurred after 8-item training but progressively improved with larger set sizes and was complete following 128-item training. A control monkey with a constant 8-item set ruled out repeated training and testing. Contrary to the unique-species account, it is argued that different species have quantitative, not qualitative, differences in abstract-concept learning.

Analysis of Variance↗

Normal olfactory discrimination learning set and facilitation of reversal learning after medial-temporal damage in rats: implications for an account of preserved learning abilities in amnesia.

Recent evidence of preserved skill learning in patients with "global" amnesia has led to the postulation of a qualitative distinction between functionally separate memory systems, one of which may remain preserved when the other is profoundly impaired. On one account, the separate memory systems support either the learning of declarative knowledge, i.e., facts and associations, or the learning of procedural knowledge, i.e., knowledge that permits the expression of skilled performance without reference to specific facts or associations. In an effort to develop a rodent model of amnesia that illustrates the same distinction between memory systems, rats were trained in a series of discrimination and reversal problems using olfaction, a sensory modality in which they rapidly learn new associations. Rats with bilateral fornix, amygdala, or combined fornix and amygdala damage learned successive two-odor discriminations as quickly as normal and sham-operated control subjects. Furthermore, all groups rapidly acquired the skills of discrimination as revealed in the development of a learning set. Subsequent presentation of a reversal of one discrimination elicited a marked dissociation among groups: Normal rats and rats with amygdala lesions required many more trials to acquire the reversal than to acquire a new discrimination problem, whereas rats with fornix lesions learned the reversal rather easily. A detailed analysis of response strategies suggested that normal rats and rats with amygdala lesions first extinguished the prior response tendencies and then abandoned the learning set skills and treated the reversal much as they did the initial discrimination problem.(ABSTRACT TRUNCATED AT 250 WORDS)

Amnesia↗

Computational principles of learning in the neocortex and hippocampus.

We present an overview of our computational approach towards understanding the different contributions of the neocortex and hippocampus in learning and memory. The approach is based on a set of principles derived from converging biological, psychological, and computational constraints. The most central principles are that the neocortex employs a slow learning rate and overlapping distributed representations to extract the general statistical structure of the environment, while the hippocampus learns rapidly, using separated representations to encode the details of specific events while suffering minimal interference. Additional principles concern the nature of learning (error-driven and Hebbian), and recall of information via pattern completion. We summarize the results of applying these principles to a wide range of phenomena in conditioning, habituation, contextual learning, recognition memory, recall, and retrograde amnesia, and we point to directions of current development.

Hippocampus↗

Preserved anterograde and retrograde memory of rapidly acquired olfactory discrminations after neurotoxic hippocampal lesions.

A forced-choice discrimination paradigm was used in two experiments, to evaluate retrograde and anterograde amnesia in rats after hippocampal ablation. In a within-subjects design (Experiment 1), rats were trained on a set of 10 olfactory discriminations 4 weeks before surgery and on a separate set of 10 discriminations 1 week before surgery. In a mixed design (Experiment 2), rats were trained on olfactory discriminations in one of three conditions: condition 1 (10 discriminations at 4 weeks before surgery); condition 2 (10 discriminations at 1 week before surgery); or condition 3 (10 discriminations at 4 weeks before surgery and 10 discriminations at 1 week before surgery). Discriminations in both experiments were rapidly learned, requiring 7-10 trials to reach criterion. After training, half of the rats in each condition received bilateral neurotoxic lesions of the hippocampus, and the other half received sham surgery. One week after surgery, all rats were given a retention test, consisting of a single critical trial for each discrimination. In both experiments, rats with selective hippocampal lesions exhibited preserved retention of these olfactory discriminations with no observable retention gradient. A postoperative acquisition test for two new discriminations indicated that anterograde memory was also preserved, while a postoperative test of spatial learning in the Morris water maze confirmed that the hippocampal lesions impaired spatial learning. Together, these experiments refute the contention that the hippocampus is requisite for (non-spatial) olfactory memory consolidation, storage, or access, despite the condition that the information be rapidly acquired.

Amnesia, Anterograde↗

Evidence for synaptic potentiation in a cortical network during learning.

The connections between the lateral olfactory tract (LOT) and layer I of the piriform cortex were used to test the idea that certain forms of learning involve potentiation of cortical synapses. Rats were trained on a series of two-odor discriminations over a period of several days after which patterned electrical stimulation (short, high frequency bursts with 5-6 bursts per second) of the LOT was used as a discriminative cue. The animals reacted to the stimulation as though it were an odor and quickly learned to respond appropriately and to distinguish between 'positive' and 'negative' electrodes. Comparisons of the monosynaptic responses in the piriform cortex evoked by single pulse stimulation of the LOT before and after learning revealed that the population synaptic responses were substantially potentiated by the training. This effect was present in an unchanged form 24 h later. Responses elicited by control stimulating electrodes were slightly or not at all affected by training to stimulation with another electrode. Synaptic potentiation was not found in a small group of rats that did not learn to respond to patterned stimulation and was also absent when the stimulation was applied to naive rats. These results provide evidence that rapid learning of a specific cue potentiates cortical synapses in a defined terminal field.

Animals↗

Disconjugate vertical memory-guided saccades to disparate targets.

We studied the binocular coordination of normal memory-guided saccades and the possibility of inducing memory-based disconjugate learning. First, we report that normal vertical memory-guided saccades to non-disparate targets are yoked vertically in the two eyes as well as visually guided vertical saccades. To induce disconjugate vertical learning, at each trial we flashed a target that was disparate (i.e. 8% more elevated or more depressed for one eye); the memory delay was 1 s. Memory-guided vertical saccades developed a vertical disconjugacy that was appropriate for the disparity of the remembered target. After 15 min of repetition, this vertical disconjugacy persisted even when the target to be remembered was no longer disparate; this indicates disconjugate vertical learning based on short-term memory. However, this was observed only for a few individual cases and its amplitude was small. This contrasts with prior findings on horizontal saccades associated with horizontal disparities. We conclude that vertical memory-based disconjugate learning is possible but very limited. Together with other studies, this study suggests that the natural vertical conjugacy of vertical saccades relies little on rapid learning mechanisms. Rather it seems to be built-in, and this is consistent with earlier electrophysiological findings.

Convergence, Ocular↗

[Exclusively extraperitoneal laparoscopic radical prostatectomy].

OBJECTIVE: To evaluate the technical feasibility, efficacy, and intraoperative and postoperative morbidity of exclusively extraperitoneal laparoscopic radical prostatectomy (RP). MATERIAL AND METHODS: From August 2000 to December 2001, 35 patients have had an extraperitoneal laparoscopic radical prostatectomy. The operation comprised an exclusively extraperitoneal 6 cm mini-laparotomy with the use of a camera and laparoscopic instruments. RP is performed via an anterograde approach, starting with release of the bladder neck. 35 patients (pts) were operated from 1st August 2000 to 1st December 2001. RESULTS: RP was performed via this approach in every case without the need for conversion or enlargement of the incision. The mean operating time was 135 min. No intraoperative complications were observed. Mean blood loss was 210 cc (< 100-350 ml). No patient required transfusion. Discharge was possible on the 5th day in 22 pts the 6th day in 10 pts and the 7th day in 3 pts. Oral feeding was resumed on D1. The bladder catheter was left in place for an average of 4.5 days. Oncological Results: 5 pts presented capsular effraction (PT3--negative fixed margin), 1 pt presented a positive margin at the apex (perineural infiltration). Follow-up is more than three months for all patients. PSA is < 0.1 in 34 of the 35 pts. Continence: at one month, 29 out of 35 pts used 0 to 1 protections/day, at the 3rd month, 33/35 no longer used any protection. Only 2 out of 35 pts used protection beyond 4 months during intense physical efforts. CONCLUSION: Radical prostatectomy can be performed satisfactorily by this technique which combines the advantages of the two surgical procedures (laparoscopic and open). The operating time is slightly longer than for conventional surgery. The technique appears to be perfectly reproducible, with a rapid learning curve. Atraumatic dissection of the prostatic apex appears to give satisfactory results in terms of urinary continence and postoperative pain is minimal allowing rapid mobilization of the patient.

Aged↗

The role of the amygdala and rostral anterior cingulate in encoding expected outcomes during learning.

Successful passive avoidance learning is thought to require the use of learned stimulus-reinforcement associations to guide decision making [Baxter, M.G., Murray, E.A., 2002. The amygdala and reward. Nature Reviews. Neuroscience 3, 563-573]. The current experiment investigated the neural correlates of successful passive avoidance learning in 19 healthy adults. Behaviorally, subjects showed a distinct pattern of performance: early indiscriminate responding to stimuli (pre-criterion performance), followed by relatively rapid learning before a plateau of successful performance (post-criterion performance). Neural responses to post-criterion correct responses were compared with neural responses to both incorrect responses and pre-criterion correct responses. Post-criterion correct responding was associated with increased activation in regions including rostral anterior cingulate, insula, caudate, hippocampal regions, and the amygdala.

Adult↗

Development of learned flavor preferences.

Rats, like humans, are born with only a few innate flavor preferences and aversions. Preferences retain great plasticity throughout the lifespan because they are sensitive to modification by experience. From an early age, rats can rapidly learn to prefer or avoid a flavor (conditioned stimulus, CS) that is associated with a positive or negative unconditioned stimulus (US). The US may be the mother's milk, social or thermotactile stimulation, or other food-related stimuli. Flavor-flavor learning occurs when the CS flavor is mixed with a naturally preferred (e.g., sweet) or avoided (e.g., bitter) US flavor. Flavor preferences and aversions are also produced by USs that have postoral positive (e.g., nutritious) or negative (e.g., toxic) actions. These types of learning appear to involve different behavioral and neural mechanisms as indicated by differences in conditioned responses, effective temporal parameters, resistance to extinction, and neurochemical mechanisms. New evidence indicates that flavor-nutrient preference learning can occur before weaning and influence food selection after weaning. Flavor conditioning not only affects food choice, but can also significantly increase food acceptance, that is, total consumption. Thus, from an early age, learning processes shape the feeding behavior of animals. While primarily serving an adaptive function, learning may play a role in biasing individuals towards excessive intake and weight gain.

Animals↗

Learning your way around town: how virtual taxicab drivers learn to use both layout and landmark information.

By having subjects drive a virtual taxicab through a computer-rendered town, we examined how landmark and layout information interact during spatial navigation. Subject-drivers searched for passengers, and then attempted to take the most efficient route to the requested destinations (one of several target stores). Experiment 1 demonstrated that subjects rapidly learn to find direct paths from random pickup locations to target stores. Experiment 2 varied the degree to which landmark and layout cues were preserved across two successively learned towns. When spatial layout was preserved, transfer was low if only target stores were altered, and high if both target stores and surrounding buildings were altered, even though in the latter case all local views were changed. This suggests that subjects can rapidly acquire a survey representation based on the spatial layout of the town and independent of local views, but that subjects will rely on local views when present, and are harmed when associations between previously learned landmarks are disrupted. We propose that spatial navigation reflects a hierarchical system in which either layout or landmark information is sufficient for orienting and wayfinding; however, when these types of cues conflict, landmarks are preferentially used.

Adult↗

Neural correlates of learned song in the avian forebrain: simultaneous representation of self and others.

Songbirds are extraordinary vocalists and sensitive listeners, singing to communicate identity, engage other birds in acoustical combat, and attract mates. These processes involve auditory plasticity in that birds rapidly learn to discriminate novel from familiar songs. Songbirds also are one of the few non-human animals that use auditory feedback to learn their vocalizations, thus auditory -- vocal interactions are likely to be important to vocal learning. Recent advances strengthen the connection between song recognition and processing of birdsong in the auditory telencephalon. New insights also have emerged into the mechanisms underlying the 'gating' of auditory responses and the emergence of highly selective responses, two processes that could facilitate auditory feedback important to song learning.

Animals↗

One-trial visual recognition in cats.

The ability of normal cats to perform delayed matching- and nonmatching-to-sample with trial-unique stimuli was investigated both in a modified Wisconsin General Testing Apparatus requiring manipulatory responses and in a Nencki-type testing room requiring locomotor responses. Cats trained in the WGTA learned the two tasks at about the same rate, on average, as that reported for monkeys. However, unlike monkeys, whose strong preference for novelty facilitates their learning of the nonmatching rule and retards their learning of the matching rule, the cats learned the two different rules at about the same rate, suggesting that cats do not share the monkey's strong preference for novelty. In contrast to their relatively rapid learning of the manipulatory versions of the two tasks, cats learned the locomotor versions only slowly or even failed to learn. Experimental analysis indicated that a major source of the cats' difficulty on these locomotor versions was interference from a strong tendency in the large testing room to use visuospatial strategies. Nevertheless, once the matching or nonmatching rule was learned at short delays, whether in the WGTA or the testing room, the cats performed at criterion levels without further training even at delays of 10 minutes, indicating that this species, like monkeys, has a highly developed long-term recognition memory ability.

Analysis of Variance↗

Nociceptive plasticity inhibits adaptive learning in the spinal cord.

Spinal plasticity is known to play a role in central neurogenic pain. Over the last 100 years researchers have found that the spinal cord is also capable of supporting other forms of plasticity including several forms of learning. To study instrumental (response-outcome) learning in the spinal cord, we use a preparation in which spinally transected rats are given shock to the hind leg when the leg is extended. The spinal cord rapidly learns to hold the leg in a flexed position when given this controllable shock. However, if shock is independent of leg position (uncontrollable shock), subjects fail to learn. Uncontrollable shock also impairs future learning. As little as 6 min of uncontrollable shock to either the leg or the tail generates a learning deficit that lasts up to 48 h. Recent data suggest links between the learning deficit and the sensitization of pain circuits associated with inflammation or injury (central sensitization). Here, we explored whether central sensitization and the spinal learning deficit share pharmacological and behavioral features. Central sensitization enhances reactivity to mechanical stimulation (allodynia) and depends on the N-methyl-d-aspartate receptor (NMDAR). The uncontrollable shock stimulus that generates a learning deficit produced a tactile allodynia (Exp. 1) and administration of the NMDAR antagonist MK-801 blocked induction of the learning deficit (Exp. 2). Finally, a treatment known to induce central sensitization, intradermal carrageenan, produced a spinal learning deficit (Exp. 3). The findings suggest that the induction of central sensitization inhibits selective response modifications.

Analysis of Variance↗

Reward-related reversal learning after surgical excisions in orbito-frontal or dorsolateral prefrontal cortex in humans.

Neurophysiological studies in primates and neuroimaging studies in humans suggest that the orbito-frontal cortex is involved in representing the reward value of stimuli and in the rapid learning and relearning of associations between visual stimuli and rewarding or punishing outcomes. In the present study, we tested patients with circumscribed surgical lesions in different regions of the frontal lobe on a new visual discrimination reversal test, which, in an fMRI study (O'Doherty, Kringelbach, Rolls, Hornak, & Andrews, 2001), produced bilateral orbito-frontal cortex activation in normal subjects. In this task, touching one of two simultaneously presented patterns produced reward or loss of imaginary money delivered on a probabilistic basis to minimize the usefulness of verbal strategies. A number of types of feedback were present on the screen. The main result was that the group of patients with bilateral orbito-frontal cortex lesions were severely impaired at the reversal task, in that they accumulated less money. These patients often failed to switch their choice of stimulus after a large loss and often did switch their choice although they had just received a reward. The investigation showed that bilateral lesions were required for this deficit, since patients with unilateral orbito-frontal cortex (or medial prefrontal cortex) lesions were not impaired in the probabilistic reversal task. The task ruled out a simple motor disinhibition as an explanation of the deficit in the bilateral orbito-frontal cortex patients, in that the patients were required to choose one of two stimuli on each trial. A comparison group of patients with dorsolateral prefrontal cortex lesions was in some cases able to do the task, and in other cases, was impaired. Posttest debriefing showed that all the dorsolateral prefrontal patients who were impaired at the task had failed to pay attention to the crucial feedback provided on the screen after each trial about the amount won or lost on each trial. In contrast, all dorsolateral patients who paid attention to this crucial feedback performed normally on the reversal task. Further, it was confirmed that the bilateral orbito-frontal cortex patients had also paid attention to this crucial feedback, but in contrast had still performed poorly at the task. The results thus show that the orbital prefrontal cortex is required bilaterally for monitoring changes in the reward value of stimuli and using this to guide behavior in the task; whereas the dorsolateral prefrontal cortex, if it produces deficits in the task, does so for reasons related to executive functions, such as the control of attention. Thus, the ability to determine which information is relevant when making a choice of pattern can be disrupted by a dorsolateral lesion on either side, whereas the ability to use this information to guide behavior is not disrupted by a unilateral lesion in either the left or the right orbito-frontal cortex, but is severely impaired by a bilateral lesion in this region. Because both abilities are important in many of the tasks and decisions that arise in the course of daily life, the present results are relevant to understanding the difficulties faced by patients after surgical excisions in different frontal brain regions.

Adult↗

Blockade of NMDA receptors in prelimbic cortex induces an enduring amnesia for odor-reward associative learning.

The competitive antagonist 2-amino-5-phosphonoeptanoic acid (APV) was injected intracerebroventricularly to determine the involvement of NMDA receptors in different stages of memory consolidation. Subsequent experiments used local injections to determine possible sites of drug action. Rats were trained in a rapidly learned olfactory task to find palatable food in a hole in a sponge impregnated with the target odor in the presence of two other sponges with nonrewarded odors. APV injections were made intracerebroventricularly 5 min or 2 hr after the end of the training, and a retention test was given 48 hr later. The results showed that blockade of NMDA receptors immediately after training induces a profound and enduring amnesia with no effect when the treatment is delayed at 2 hr after training. To address the question of the effective sites of action of the intracerebroventricular treatment, APV injections into the hippocampus and into the prelimblic region of the frontal cortex (PLC) were made. Blockade of NMDA receptors into the PLC but not into the hippocampus impaired memory formation of the odor-reward association. The amnesia is not transient, because the retention tests were made 48 hr after training. These results underlie the role of NMDA receptors in the early stage of consolidation of a simple odor-reward associative memory and confirm the role of the PLC in the consolidation of long-term memory.

Amnesia↗

How sleep affects the developmental learning of bird song.

Sleep affects learning and development in humans and other animals, but the role of sleep in developmental learning has never been examined. Here we show the effects of night-sleep on song development in the zebra finch by recording and analysing the entire song ontogeny. During periods of rapid learning we observed a pronounced deterioration in song structure after night-sleep. The song regained structure after intense morning singing. Daily improvement in similarity to the tutored song occurred during the late phase of this morning recovery; little further improvement occurred thereafter. Furthermore, birds that showed stronger post-sleep deterioration during development achieved a better final imitation. The effect diminished with age. Our experiments showed that these oscillations were not a result of sleep inertia or lack of practice, indicating the possible involvement of an active process, perhaps neural song-replay during sleep. We suggest that these oscillations correspond to competing demands of plasticity and consolidation during learning, creating repeated opportunities to reshape previously learned motor skills.

Acoustic Stimulation↗

Mapping of olfactory memory circuits: region-specific c-fos activation after odor-reward associative learning or after its retrieval.

Although there is growing knowledge about intracellular mechanisms underlying neuronal plasticity and memory consolidation and reconsolidation after retrieval, information concerning the interaction among brain areas during formation and retrieval of memory is relatively sparse and fragmented. Addressing this question requires simultaneous monitoring of activity in multiple brain regions during learning, the post-acquisition consolidation period, and retrieval and subsequent reconsolidation. Immunoreaction to the immediate early gene c-fos is a powerful tool to mark neuronal activation of specific populations of neurons. Using this method, we are able to report, for the first time, post-training activation of a network of closely related brain regions, particularly in the frontal cortex and the basolateral amygdala (BLA), that is specific to the learning of an odor-reward association. On the other hand, retrieval of a well-established associative memory trace does not seem to differentially activate the same regions. The amygdala, in particular, is not engaged after retrieval, whereas the lateral habenula (LHab) shows strong activation that is restricted to animals having previously learned the association. Although intracellular mechanisms may be similar during consolidation and reconsolidation, this study indicates that different brain circuits are involved in the two processes, at least with respect to a rapidly learned olfactory task.

Amygdala↗

The anterior cerebellar vermis: essential involvement in classically conditioned bradycardia in the rabbit.

The effects of lesions of the cerebellum on the acquisition and retention of aversive Pavlovian conditioned bradycardia were examined in rabbits. Lesions of the anterior cerebellar vermis severely attenuated the acquisition of simple conditioned bradycardia without disrupting baseline heart rate (HR), or unconditioned HR responses. Also, lesions of the vermis performed after the acquisition of conditioned bradycardia eliminated evidence of prior conditioning. Bilateral lesions of the cerebellar hemispheres did not affect conditioned or unconditioned HR responses. These results were interpreted to indicate that anterior vermis lesions specifically disrupted part of an essential conditioned response pathway without interfering with the neural circuits that mediate unconditioned HR responding. These lesion data, coupled with recent electrophysiological evidence of learning-related changes in neuronal activity within the anterior vermis of the fear-conditioned rabbit, suggest that the anterior cerebellar vermis is critically involved in the acquisition and retention of this rapidly learned autonomic conditioned response.

Acoustic Stimulation↗