Spatial memory deficits in a virtual radial arm maze in amnesic participants with hippocampal damage.

Extensive research with laboratory animals indicates that the hippocampus is crucial for the formation and use of spatial memory. Hippocampal lesions in rodents impair spatial memory on radial arm maze tasks. It is unknown whether amnesic patients with hippocampal damage would exhibit similar impairments on a virtual version of a radial arm maze. To evaluate the importance of the hippocampus in spatial learning and memory, we tested amnesic participants with hippocampal damage in a virtual radial arm maze environment. The virtual radial arm maze required participants to learn and remember 4 rewarded arms of 8 total arms. Spatial learning and memory were assessed using the participants' ability to use salient distal cues in the virtual room to remember the 4 rewarded arms. Amnesic participants' latencies were longer and distance traveled was greater to the rewarded arms compared with nonamnesic participants. Amnesic participants made more errors than nonamnesic participants by either entering nonrewarded arms or by revisiting previously entered arms. These data are analogous to previous animal research. Overall, the human hippocampus is necessary for spatial memory and navigation in a virtual radial arm maze task. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ontogeny of contextual fear conditioning in rats: Implications for consolidation, infantile amnesia, and hippocampal system function.

Presents developmental evidence that contextual fear conditioning is supported by a short-term memory system that supports conditioning immediately after a shock and by a long-term memory system that supports contextual conditioning 24 hrs after training. This is based on the finding that after 1 conditioning trial, rats 18–32 days old show the same amount of conditioned freezing when tested immediately after conditioning but 18-day-old rats show much less conditioned freezing than the older rats when the retention interval is 24 hrs. The data also suggest that the long-term memory representation of context that mediates conditioned fear is not available until several hours after the conditioning trial. Implications of these findings for memory consolidation processes, infantile amnesia, and hippocampal formation development are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Modafinil and memory: Effects of modafinil on Morris water maze learning and Pavlovian fear conditioning.

Modafinil has been shown to promote wakefulness and some studies suggest the drug can improve cognitive function. Because of many similarities, the mechanism of action may be comparable to classical psychostimulants, although the exact mechanisms of modafinil's actions in wakefulness and cognitive enhancement are unknown. The current study aims to further examine the effects of modafinil as a cognitive enhancer on hippocampus-dependent memory in mice. A high dose of modafinil (75 mg/kg ip) given before training improved acquisition on a Morris water maze. When given only before testing, modafinil did not affect water maze performance. We also examined modafinil (0.075 to 75 mg/kg) on Pavlovian fear conditioning. A low dose of pretraining modafinil (0.75 mg/kg) enhanced memory of contextual fear conditioning (tested off-drug 1 week later) whereas a high dose (75 mg/kg) disrupted memory. Pretraining modafinil did not affect cued conditioning at any dose tested, and immediate posttraining modafinil had no effect on either cued or contextual fear. These results suggest that modafinil's effects of memory are more selective than amphetamine or cocaine and specific to hippocampus-dependent memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Age-related deficits in mice performing working memory tasks in a water maze.

This study determined whether mice exhibit spatial working memory deficits with increased age. C57BL/6JNia mice of 3 different ages were tested in the Morris water maze with 2 protocols designed to assess immediate and delayed working memory abilities. Young mice required multiple trials in order to show improvements in the working memory task. Deficits in immediate working memory were detected in both 10- and 24- to 26-month-old mice. Reference memory deficits and declines in performance in the delayed working memory task were only seen in 24- to 26-month-olds. This increased susceptibility of immediate working memory processes to the aging process in mice may be related to their need for more rehearsal in the water maze than other species. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Operant conditioning of hippocampal theta: Dissociating reward from performance deficits.

Dopaminergic blocking agents have been known to suppress intracranial self-stimulation, but whether the suppression results from a reduction in the rewarding value of stimulation or from motor deficits has remained controversial. We have resolved this controversy by developing an operant technique minimally dependent on motor activity; rats were trained to perform a bar-holding response for 3s or to produce hippocampal theta waves for 3s when the bar was retracted. Decamethonium bromide (a muscle relaxant) reduced bar holding without affecting theta production for brain stimulation. Pimozide (a dopaminergic blocking-agent) reduced both bar holding and theta production for stimulation, though rats were still capable of making the theta response at a rate comparable to the preinjection rate. Dopaminergic blocking at low doses reduces the rewarding value of brain stimulation at the level of the lateral hypothalamus. The method described in this report has wide applicability. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hippocampectomy disrupts auditory trace fear conditioning and contextual fear conditioning in the rat

The hippocampus is believed to be an important structure for learning tasks that require temporal processing of information. The trace classical conditioning paradigm requires temporal processing because the conditioned stimulus (CS) and the unconditioned stimulus (US) are temporally separated by an empty trace interval. The present study sought to determine whether the hippocampus was necessary for rats to perform a classical trace fear conditioning task in which each of 10 trials consisted of an auditory tone CS (1 5-s duration) followed by an empty 30-s trace interval and then a fear-producing floor-shock US (0.5-s duration). Several weeks prior to training, animals were anesthetized and given aspiration lesions of the neocortex (NEO; n = 6), hippocampus and overlying neocortex (HIPP; n = 7), or no lesions at all (control; n = 6). Approximately 24 h after trace conditioning, NEO and control animals showed a significant decrease in movement to a CS-alone presentation that was indicative of a conditioned fear response. Animals in the HIPP group did not show conditioned fear responses to the CS alone, nor did a pseudoconditioning group (n = 7) that was trained with unpaired CSs and USs. Furthermore, all groups except the HIPP group showed conditioned fear responses to the original context in which they received shock USs. One week later, HIPP, NEO, and control animals received delay fear-conditioning trials with no trace interval separating the CS and US. Six of seven HIPP animals could perform the delay version, but none could perform the trace version. This result suggests that the trace fear task is a reliable and useful model for examining the neural mechanisms of hippocampally dependent learning.     

Flexible memory processing by rats: Use of prospective and retrospective information in the radial maze.

Investigated the content of the memory used by rats in mediating retention intervals interpolated during performance in a 12-arm radial maze, using 10 Sprague-Dawley rats in Exps I and II and 21 Long-Evans rats in Exps III and IV. The delay occurred following either the 2nd, 4th, 6th, 8th, or 10th choice. A 15-min delay had the greatest disruptive effect when interpolated in the middle of the choice sequence and less of an effect when it occurred either earlier or later. This pattern was obtained when either a free- or forced-choice procedure was used prior to the delay and regardless of whether postdelay testing consisted of completion of the maze or 2-alternative forced-choice tests. Assuming that the disruptive effect of a delay is a function of memory load, this implies that Ss used information about previously visited arms (retrospective memory) following an earlier interpolated delay but information about anticipated choices (prospective memory) following a delay interpolated late in the choice sequence. There appeared to be a recency effect only in the early and middle delay conditions. Data provide converging evidence for the dual-code hypothesis. No evidence for prospective memory was obtained following a 60-min delay. (26 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Impaired fear memories are correlated with subregion-specific deficits in hippocampal and amygdalar LTP.

Inbred mouse strains have different genetic backgrounds that likely influence memory and long-term potentiation (LTP). LTP, a form of synaptic plasticity, is a candidate cellular mechanism for some forms of learning and memory. Strains with impaired fear memory may have selective LTP deficits in different hippocampal subregions or in the amygdala. The authors assessed fear memory in 4 inbred strains: C57BL/6NCrlBR (B6), 129S1/SvImJ (129), C3H/HeJ (C3H), and DBA/2J (D2). The authors also measured LTP in the hippocampal Schaeffer collateral (SC) and medial perforant pathways (MPP) and in the basolateral amygdala. Contextual and cued fear memory, and SC and amygdalar LTP, were intact in B6 and 129, but all were impaired in C3H and D2. MPP LTP was similar in all 4 strains. Thus, SC, but not MPP, LTP correlates with hippocampus-dependent contextual memory expression, and amygdalar LTP correlates with amygdala-dependent cued memory expression, in these inbred strains. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of ethanol on encoding, consolidation, and expression of extinction following contextual fear conditioning.

Studies of contextual fear conditioning have found that ethanol administered prior to a conditioning session impairs the conditioned freezing response during a test session the next day. The present experiments examined the effects of ethanol on extinction, the loss of conditioned responding that occurs as the animal learns that a previously conditioned context no longer signals shock. Ethanol (1.5 g/kg) administered prior to single (Experiment 1) or multiple (Experiment 2) extinction sessions impaired extinction. Ethanol administered prior to a test session disrupted the expression of freezing after extinction (Experiments 3-5). There was some evidence that ethanol served as an internal stimulus signaling the operation of conditioning or extinction contingencies (Experiments 4-5). In Experiment 6, postsession injections of 1.5 g/kg ethanol had no effect on extinction with brief (3 min) or long (24 min) exposures to the context, but injections of 3 g/kg after long exposures impaired extinction. Together, these results indicate that ethanol affects extinction by acting on multiple learning and performance processes, including attention, memory encoding, and memory expression. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Spatial memory in pigeons on the radial maze.

A series of 7 experiments with 10 pigeons showed, contrary to recent suggestions that pigeons show little or no spatial memory on the radial maze, highly accurate performance by Ss on an 8-arm radial maze. In Exp I, Ss were trained on successive phases that raised the number of alleys to be remembered from 1 to 4. In Exp II, Ss were allowed to search the maze for food with all 8 arms open. Measures of spatial memory showed that Ss performed at a level equivalent to that found with rats in previous research by A. B. Bond et al (see record 1982-25052-001). In Exp III, testing with massed trials revealed proactive interference. Ss were able to form reference memory for subsets of baited and unbaited alleys in Exp VI. In Exp VII, Ss learned about quantities of food associated with 4 different alleys and ordered their alley choices from the largest to the smallest reward. Contrary to the previous findings with rats, Ss in Exp IV showed forgetting over retention intervals of 0–360 sec between forced and free choices. It is concluded that spatial memory in pigeons generally shows the same properties as that in rats. (49 ref) (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Partial hippocampal kindling affects retention but not acquisition and place but not cue tasks on the radial arm maze

The performance of rats that were partially kindled in the hippocampus was assessed on an 8-arm radial arm maze with 4 baited arms. In rats first trained and then kindled, deficits were found on a place task in which rats reached the goal arms of the maze using salient extramaze spatial cues, but not on an intramaze cue task in which rats reached the goal arms using salient intramaze cues. Acquisition of a new place task on the maze was not different between kindled and control rats. In conclusion, partial hippocampal kindling disrupted the retention but not the acquisition of a spatial or place task; retention of a nonspatial cue task was not disrupted.     

Memory consolidation and the hippocampal system

The dihydropyridines (DHP) receptor forms a high threshold L-type calcium channel in various excitable cells. In skeletal and cardiac muscle cells, a DHP receptor antagonist blocks not only the voltage-gated calcium current but also immobilizes the charge movement linked to the receptor. The DHP receptor is also present in cerebellar Purkinje neurons. Previously, we showed that nifedipine immobilizes a part of the charge movement but has no effect on the calcium channel current recorded in freshly dissociated mice Purkinje neurons. We report here the effect of other families of DHP receptor antagonists, benzothiazepines and phenylalkylamines, on the physiological properties of this receptor in mouse Purkinje neurons.     

Extinction in fear conditioning: effects on startle modulation and evaluative self-reports

gamma-Hydroxybutyric acid (GHB) is unfamiliar to many physicians in the United States but enjoys clinical use elsewhere for applications in resuscitation, anesthesia, and addiction therapy. Use within the United States is restricted to Food and Drug Administration-approved clinical trials for treatment of narcolepsy. Recently illicit use of GHB has emerged within the United States where it is distributed for purported euphoric and "fat-burning" metabolic effects. Clinical effects can be severe, progressing rapidly to respiratory arrest and death. We provide an updated comprehensive review of the literature with particular emphasis on toxicology, including GHB pharmacodynamics, clinical effects, and suggestions for overdose management. Recommended management of acute GHB intoxication includes prevention of aspiration, use of atropine for persistent symptomatic bradycardia, consideration of neostigmine as a reversal agent, and treatment for coingested substances. Emergency physicians are urged to become familiar with GHB because of its potential for severe morbidity as well as its potential use as a future resuscitative agent.     

Arrest of adult hippocampal neurogenesis in mice impairs single- but not multiple-trial contextual fear conditioning.

The role of adult hippocampal neurogenesis in contextual fear conditioning (CFC) is debated. Several studies demonstrated that blocking adult hippocampal neurogenesis in rodents impairs CFC, while several other studies failed to observe an impairment. We sought to determine whether different CFC methods vary in their sensitivity to the arrest of adult neurogenesis. Adult neurogenesis was arrested in mice using low-dose, targeted x-irradiation, and the effects of irradiation were assayed in conditioning procedures that varied in the use of a discrete conditioned stimulus, the number of trials administered, and the final level of conditioning produced. We demonstrate that irradiation impairs CFC in mice when a single-trial CFC procedure is used but not when multiple-trial procedures are used, regardless of the final level of contextual fear produced. In addition, we show that the irradiation-induced deficit in single-trial CFC can be rescued by providing preexposure to the conditioning context. These results indicate that adult hippocampal neurogenesis is required for CFC in mice only when brief training is provided. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Simultaneous and backward fear conditioning in the rat.

Examined simultaneous and backward Pavlovian conditioning paradigms using a UCS event which was longer in duration than the CS. 3 experiments with male Sprague-Dawley rats (N = 96) paired a 4-sec electric shock with a 2-sec tone-light stimulus under conditions in which the onset of the stimulus occurred 0, .25, 1.0, 2.0, 4.0, or 4.5 sec. after the onset of the shock. Relative to nonpaired control procedures, response-contingent presentations of the CSs in these paradigms significantly suppressed a food-rewarded free operant, indicating that these temporal relationships can produce excitatory associative conditioning. It is suggested that the distinctions between "forward," "simultaneous," and "backward" procedures be modified to include a more molecular analysis of the UCS event. (21 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neurotoxic or electrolytic lesions of the ventral subiculum produce deficits in the acquisition and expression of Pavlovian fear conditioning in rats.

The effects of neurotoxic or electrolytic ventral subicular (vSUB) lesions on the acquisition and expression of Pavlovian fear conditioning in rats were examined. Conditioning consisted of the delivery of tone–footshock trials in a novel observation chamber, and freezing served as the measure of conditional fear. Pretraining vSUB lesions produced a severe tone freezing deficit and a modest context freezing deficit, whereas posttraining lesions produced severe deficits in freezing to both a tone -and a context conditional stimulus (CS). Similar impairments were produced by neurotoxic and electrolytic lesions. Increases in motor activity associated with the lesions could not account for freezing deficits. These results reveal that neurons in the vSUB have an important role in both the acquisition and expression of Pavlovian fear conditioning to contextual and acoustic CSs. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Age-related changes in processing auditory stimuli during visual attention: Evidence for deficits in inhibitory control and sensory memory.

Age-related declines in attention and cognition have been associated with a difficulty in inhibiting the processing of task-irrelevant information (i.e., the inhibitory deficit hypothesis). However, evidence supporting the inhibitory deficit hypothesis remains equivocal, in part because of complexities in examining the processing of irrelevant stimuli using purely behavioral techniques. The effects of age on the processing of task-irrelevant stimuli were examined using scalp-recorded event-related brain potentials. Participants performed a visual discrimination task while standard and deviant auditory stimuli were presented in the background. Deviant auditory stimuli generated a mismatch negativity (MMN) wave that decreased with age, in part because of an age-related enhancement in sensory-evoked responses. The age-related changes in processing task-irrelevant auditory stimuli are consistent with the inhibitory deficit hypothesis and suggest that impaired inhibitory control of sensory input may play a role in the age-related declines in performance during selective attention tasks. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Parallel augmentation of hippocampal long-term potentiation, theta rhythm, and contextual fear conditioning in water-deprived rats.

The influence of water deprivation on hippocampal long-term potentiation (LTP), theta rhythm, and contextual fear conditioning in 56 adult male rats was examined. In Exp 1, hippocampal EEG activity and perforant path LTP were assessed in pentobarbital-anesthetized rats. Water deprivation did not affect baseline cell excitability or low-frequency synaptic transmission in the dentate gyrus, but it increased the magnitude of perforant path LTP and elevated the proportion of theta rhythm in the EEG. In Exp 2, rats were classically conditioned to fear a novel context through the use of aversive footshocks. Water deprivation facilitated the rate of contextual fear conditioning but did not alter the asymptote of learning. Exp 3 demonstrated that the facilitation of contextual fear conditioning was not due to a change in unconditional shock sensitivity. These results suggest that water deprivation exerts an influence on contextual fear conditioning by modulating hippocampal LTP and theta rhythm and that these processes serve to encode contextual information during learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Spatial memory in pigeons on a four-arm radial maze.

Examined spatial memory in 6, 8-arm maze experienced pigeons, using a 4-arm radial maze. The maze arms were spaced at 90° intervals, extending radially from a central choice area. Ss were forced into 3 arms, then permitted 2 choices to enter the remaining arm. Five Ss chose accurately (90% correct) with delays of 5 min or less, their choices depended on extramaze cues, and the food in the target arm provided no essential cues. After an incorrect 1st choice, Ss' 2nd choices were more accurate than chance. Data suggest that, while spatial memory has many similar characteristics in rats and pigeons, pigeon spatial memory appears less durable. (French abstract) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Potentiation and overshadowing in Pavlovian fear conditioning.

The present experiments addressed a fundamental discrepancy in the Pavlovian conditioning literature concerning responding to a target cue following compound reinforced training with another cue of higher salience. Experiment 1 identified one determinant of whether the target cue will be overshadowed or potentiated by the more salient cue, namely contiguity between compound CS termination and US presentation. Overshadowing and potentiation were observed with delay and trace procedures, respectively. Experiments 2 and 3 contrasted elemental and configural explanations of potentiation. Both experiments supported a configural account. Experiments 3 and 4, by manipulating prior learning experiences to bias subjects to encode the same compound elementally or configurally, demonstrated decreased potentiation and overshadowing, respectively. Overall, these experiments demonstrate potentiation with nontaste stimuli and identify one variable that determines whether overshadowing or potentiation will occur. Moreover, they show that prior experiences can determine how a compound is encoded and are compatible with the idea of flexible encoding as a principle of information processing. (PsycINFO Database Record (c) 2010 APA, all rights reserved)