Medial septal lesions disrupt spatial, but not nonspatial, working memory in rats.

In Exp 1, rats with small medial septal lesions were less able than were control rats to remember the location of the arm of a Y maze they had been forced to enter on the preceding sample run. Moreover, as the retention interval between the sample and choice runs on this spatial delayed nonmatching-to-sample (DNMTS) task was increased to 1 and 2 min, the magnitude of the deficit increased. In contrast, these same lesioned rats were not deficient in Exp 2 in their ability to remember the object they had encountered in the straight alley on the sample run. In fact, when the retention interval was increased to 1 min on this nonspatial DNMTS task, the rats with medial septal lesions were more accurate than were the controls. This pattern of results did not appear to be due to task difficulty, recovery of function, or sequence of training. Rather, these results indicate that damage to the septohippocampal system disrupts spatial working memory more than it disrupts nonspatial working memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Fibrinogen and cardiovascular risk

We trained 24 rats to perform an eight-arm radial maze task and then assigned them with a matching procedure to one of three treatments: sham surgery or lesions of the projection areas of the mediodorsal thalamic nucleus (MDn) in the medial wall (MW) or in both the MW and rhinal sulcal (RS) areas of frontal cortex. After recovery we trained the rats to perform six tasks, beginning with the standard eight-arm task, followed by two versions of a four forced choice procedure, and then three versions of a two-choice delayed-nonmatching-to-sample (DNMTS) task. The two lesion groups performed comparably on all tasks, showing that impairments were not exacerbated by extension of the MW lesion to include all cortical areas innervated by MDn. As in previous studies, frontal animals performed the radial maze task poorly immediately after surgery but improved with subsequent training. Controlling the order of the arm entries by opening the first four gates in a random sequence had little effect on performance, although frontal animals were impaired when lengthy delays (5 or 15 min) were imposed after the last of the four forced entries. Frontal animals were not impaired on two-choice DNMTS when the arms used for training were selected at random from the eight alternatives on a trial by trial basis, even when visual cues were eliminated by darkening the room and covering the maze. Frontal animals were significantly impaired when the selection of sample and choice arms was limited to the same two alternatives on every trial. This finding may explain the reported sensitivity of DNMTS to the effects of frontal lesions when training is carried out in operant chambers.     

MK-801 prevents brain lesions and delayed-nonmatching-to-sample deficits produced by pyrithiamine-induced encephalopathy in rats.

Rats were trained on a spatial delayed-nonmatching-to-sample (DNMTS) task and assigned by block randomization to 1 of 4 treatments: pyrithiamine-induced thiamine deficiency (PTD), PTD with administration of MK-801 after 12 days, control with MK-801 treatment, and control without MK-801. After 15 days of treatment followed by 21 days of recovery, the PTD rats showed significant deficits for DNMTS accuracy at retention intervals (RIs) that ranged from 3.0 sec to 15.0 sec, the RIs that produced 75% accuracy on DNMTS in staircase training, and the rate at which a novel radial arm maze task was learned. The PTD-treated rats had consistent lesions in the thalamus and the mammillary bodies. MK-801 protected rats from both behavioral deficits and brain lesions (assessed quantitatively and qualitatively) that were produced by the PTD treatment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Scopolamine affects response-to-change test involving 20-min retention interval after locomotor exploration in rats

The tendency to select the T-maze arm that has been changed in brightness between two successive trials (response-to-change) was investigated. Our previous findings indicated that scopolamine injections (1.0 mg/kg) impaired responding to change of brightness in a choice trial (trial II) following a 1-min retention interval, when in the first acquisition trial rats could only inspect the white-black T-maze arms through transparent partitions (the passive test). The drug was ineffective when rats were allowed locomotor exploration of the maze (the active test). The aim of the present experiment was to investigate the effect of the same dose of scopolamine on the active test involving a longer 20-min retention interval between the acquisition trial and the choice trial. The effect of cue salience also was examined by using grey-black arms. Rats injected with scopolamine (Scopo) 20 min before the acquisition trial performed in the white-black maze on the chance level, whereas saline-injected rats (Sal) showed significant preference for the changed arm. Decreasing the cue salience impaired response-to-change in Sal rats (50% of changed arm choices) but had no further effect on performance of Scopo rats, presumably because of a floor effect. The postacquisition injection had a somewhat stronger effect than the injections preceding acquisition, which most probably reflects the state dependency phenomenon. The deficient performance due to scopolamine treatment that appeared in the present study at a longer retention interval could be interpreted in terms of increased forgetting.     

Spatial delayed matching-to-sample performance by rats: Learning, memory, and proactive interference.

Nine Sprague-Dawley rats were trained in a 3-alternative delayed matching-to-sample task in which the samples were rewarded forced choices of 1 arm of a 3-arm starburst maze, and retention was indicated by returning to that arm following a delay or retention interval. If the S made an error on its 1st free choice of a trial, the chosen arm was blocked off, and the S was allowed a 2nd choice between the remaining 2 arms. Ss quickly acquired this task. Exp II showed that choice accuracy was lower with 1-min retention intervals than with immediate tests. In Exp III, there was evidence for 2 separable proactive interference effects. The degree to which prior events influenced responding decreased as the intertrial interval increased. Choice accuracy improved with increasing intertrial interval and declined with increasing retention interval durations. Additionally, choice accuracy was higher when the sample from the previous trial matched the sample from the current trial and lower when they did not match. These results suggest that encoding information about visited spatial locations is a gradual process rather than an all-or-none process in rats. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A comparison of temporal decay in place memory tasks in rats (Rattus norvegicus) with lesions affecting thalamus, frontal cortex, or the hippocampal system

Three experiments compared the effects of lesioning areas of thalamus, cortex, and the hippocampal system on delayed matching (DMTS) and nonmatching (DNMTS) to sample. Temporal decay was measured by comparing performances at different retention intervals (RIs) for rats trained to stability. Lesions of the lateral-internal medullary lamina site in thalamus and the medial wall area in frontal cortex produced impairments that were significantly greater than for lesions of the mediodorsal nucleus in thalamus, the fornix, or the dorsal hippocampus. The effects of lesions on temporal decay differed depending on how RIs were manipulated. When RIs were manipulated within training sessions, the DMTS and DNMTS impairments were delay independent (i.e., none of the lesions increased the rate of temporal decay). When RIs were manipulated between sessions, thalamic lesions were associated with an increase in the rate of temporal decay of DNMTS.     

Working memory, response selection, and effortful processing in rats with medial prefrontal lesions.

Examined the effects of lesions of the prelimbic area of the prefrontal cortex on acquisition and retention of nonmatching (NMTS) and matching-to-sample (MTS) tasks. 64 male rats participated. Both tasks involved a reference and a working memory component, but only working memory was impaired by the lesions. A comparison of the 2 tasks revealed quantitatively similar deficits in postoperatively trained rats. In preoperatively trained rats, however, the deficits were more important in the MTS task than in the NMTS task. In addition, an effect of interference between successive trials was observed in the NMTS task but not in the MTS task. Perseverative tendencies were observed in the MTS task only. Results suggest that prefrontal lesions induce working memory deficits as a result of poor temporal encoding and increased susceptibility to interference, and impair effortful processing, such as that engaged in response selection mechanisms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of 3,3'-iminodipropionitrile on acquisition and performance of spatial tasks in rats

3,3'-Iminodipropionitrile (IDPN) has been reported to disrupt learning and memory in rats (24). The present work addressed the effects of IDPN on tasks requiring the use of spatial information. Separate groups of male rats were dosed with IDPN (IP, in 1 ml/kg saline) for 3 consecutive days and tested in the following procedures: (a) step-through passive avoidance conditioning (0, 100, 150, and 200 mg/kg/day); (b) Morris water maze (MWM) acquisition and retention (0, 125, 150, 175, and 200 mg/kg/day); (c) radial arm maze (RAM) acquisition (0, 100, 200, and 400 mg/kg/day); (d) RAM steady-state performance (0, 200, and 400 mg/kg/day); (e) repeated acquisition in the RAM (0, and 200 mg/kg/day). The vestibular toxicity of IDPN resulted in alterations in spontaneous behavior or swimming deficits in 5 of 8 rats treated with 175 mg/kg/day and in all the animals dosed with 200 or 400 mg/kg/day. IDPN increased step-through PA latencies at 200 mg/kg/day but not at lower doses. In the MWM, no performance deficits were observed at the dose levels preserving the swimming ability of the animals. In both the acquisition and the steady-state RAM tasks, IDPN (400 mg/kg/day) induced an increase in both choice errors and perseverative errors. In the RAM repeated acquisition paradigm, IDPN (200 mg/kg/day) induced performance deficits that included a decreased rate of within-session reduction in errors. The present data show that IDPN disrupts performance of tasks requiring spatial learning and memory and indicate that these deficits can be in part caused by an acquisition deficit.     

Effects of amygdaloid and amygdaloid-hippocampal lesions on object recognition and spatial working memory in rats.

Neurotoxic lesions of the amygdala did not affect the postoperative acquisition of a nonspatial test of object recognition (delayed nonmatching to sample) even when retention delays were increased from 0 sec to 20 or 60 sec, or when test stimuli were deliberately repeated within a session. Although these amygdaloid lesions did not alter forced-choice spatial alternation, they slightly increased neophobic responses to novel foods and environments. In contrast, combined amygdalohippocampal (A?+?H) lesions impaired performance on the object recognition task when the retention intervals were increased beyond 0 sec and when test stimuli were repeated within a session. The A?+?H rats were also severely impaired on the spatial alternation task, and they showed reduced neophobia. Comparisons with a previous study show that damage to the amygdala or hippocampus does not affect object recognition, whereas A?+?H damage produces clear deficits. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Radio-frequency lesions of the thalamus produce delayed-nonmatching-to-sample impairments comparable to pyrithiamine-induced encephalopathy in rats.

Rats were trained and matched on a delayed-nonmatching-to-sample (DNMTS) task and randomly assigned to treatment. In Exp 1, radio-frequency (RF) lesions were aimed at lateral portions of the internal medullary lamina (L-IML), midline thalamus (MT), mammillary bodies (MB), and the combination of MT and MB. In Exp 2, RF lesions were aimed at the fornix. After recovery, DNMTS was retrained at retention intervals of 3.0–28.0 sec, the critical retention level for 75% DNMTS accuracy was determined by a staircase procedure, and spontaneous exploration was observed in an open field. L-IML lesions produced significant deficits on DNMTS and exploratory behavior that were comparable to deficits on the same tasks in rats recovered from pyrithiamine-induced thiamine deficiency. Fornix lesions produced significant DNMTS deficits that were substantially smaller than for the L-IML group. The MT, MB, and MT?+?MB treatments had no significant effect on DNMTS. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential effects of selective immunotoxic lesions of medial septal cholinergic cells on spatial working and reference memory.

The effect of injection into the medial septum of a toxin selective for cholinergic neurons, 192 IgG-saporin, was examined in rats trained to perform 2 versions of the radial 8-arm maze task. Rats were first trained to perform a task with varying delays (0, 1, 2 min) imposed between the 4th correct arm choice and access to all 8 arms. Lesioned rats made significantly more errors in the first 4 choices compared with controls and significantly more errors after delays; however, this effect was not delay dependent. Rats were then trained on a different version of this 8-arm maze task in which they learned to avoid 2 arms that were never baited. There was no treatment effect on acquisition of this task. These data are consistent with the hypothesis that the cholinergic projection to the hippocampus facilitates the acquisition of information into the system responsible for short-term memory for locations visited (spatial working memory) but is not involved in retention of this information. It also appears to play no role in either the acquisition or retention of place-nonreward associations (spatial reference memory). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Does a cognitive map guide choices in the radial-arm maze?

15 rats performed in a standard radial-arm maze task (Exp 1) and in a modified task with a set of forced choices and a 15-min retention interval prior to completion of the maze (Exp 2). In addition to the standard measure of choice in the radial-arm maze, orientation toward arms was measured and considered to constitute go–no-go "microchoice" decisions. Rats investigated but rejected many arms. A model of choice was developed in which it was assumed that choice decisions about arms were made independently and that microchoices were not selectively guided toward baited arms. The model performed nearly as well as the rats. These results place important limitations on the theory that choice behavior in the radial-arm maze is guided by a cognitive map. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Rats perform better on spatial than brightness delayed matching-to-sample water-escape due to an unlearned bias to use spatial cues

Rats readily acquire water-escape spatial delayed matching-to-sample (DMTS) tasks and show excellent performance with retention intervals as long as 120 m (17). They also acquire the task more readily with a 5-min retention interval (RI) than with a 1-min RI (16). To determine if these observations are unique to spatial DMTS, or are also true of nonspatial water-escape DMTS, 75-day-old rats were compared on acquisition and subsequent retention of spatial and brightness DMTS. A larger proportion of the rats tested on the spatial problem were able to acquire the task, made fewer acquisition errors, and demonstrated better retention when tested at RIs of 1, 5, 15, 30, 60, and 120 min than did the rats tested on the brightness problem. Acquisition RI did not affect the rate of acquisition on either task. Examination of perserveration errors, the occurrence of intrusions, and position-congruent performance (escape platform in the same physical location on both runs of a trial) revealed that the choices of brightness-trained rats were often more influenced by spatial than brightness cues, suggesting that rats have an unlearned bias to use spatial cues in water-escape DMTS tasks.     

Performance of four-seed caching corvid species in operant tests of nonspatial and spatial memory.

The performance of 4 seed-caching corvid species was tested using 2 different operant nonmatching tasks. These species differ in their dependence on stored food, and differences in spatial memory tests have been correlated with better performance by the more cache-dependent species. Acquisition and retention of a color non-matching-to-sample task was tested in Experiment 1. Acquisition of the color task was not correlated with cache dependence, and no differences between species in performance during memory testing were found. Acquisition and retention of an operant spatial non-matching-to-sample task was tested in Experiment 2. Species differences in the spatial task were found for acquisition and during retention testing. The influence of natural history on the evolution of memory is discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Medial temporal lesions in monkeys impair memory on a variety of tasks sensitive to human amnesia.

Relative to 3 unoperated controls, 4 cynomolgus monkeys with conjoint bilateral lesions of the hippocampus and amygdala were impaired on 4 tests of memory—delayed retention of object discriminations, concurrent discrimination, delayed response, and delayed nonmatching to sample. In 3 of the tasks, relatively long-delay intervals between training and test trials were used, and in 2 tasks, distraction was introduced during the delay intervals. The severity of the impairment increased with the length of the delay, and distraction markedly increased the memory impairment. For 1 task given on 2 occasions (delayed nonmatching to sample), the severity of the impairment was unchanged over 1.5 yrs. It is concluded that monkeys with medial temporal lesions constitute an animal model of human amnesia and that the 4 tasks used in the present study appear to constitute a sensitive and appropriate battery that could be used in other studies of the neuroanatomy of memory functions in the monkey. (47 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Analysis of anatomical sites at which galanin impairs delayed nonmatching to sample in rats.

Galanin, a neuropeptide that coexists with acetylcholine in the septohippocampal pathway of the rat, impairs operant delayed nonmatching to sample (DNMTS) when administered intracerebroventricular/ly (icv). Microinjection experiments were conducted with 40 male rats to determine the anatomical site or sites at which galanin acts to disrupt DNMTS. Galanin (0.1, 0.4, or 1.6 nmol) was microinjected into the ventral hippocampus, amygdala, nucleus basalis magnocellularis, prefrontal cortex, or entorhinal cortex. Galanin disrupted DNMTS in a dose-dependent manner when microinjected into the ventral hippocampus but not at the other sites tested. These findings are consistent with the ability of galanin to inhibit physiological and biochemical actions of acetylcholine in the ventral hippocampus. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential effects of posterior septal lesions on dispositional and representational memory.

[Correction Notice: An erratum for this article was reported in Vol 101(1) of Behavioral Neuroscience (see record 2008-10683-001). A phrase was erroneously deleted from the text. In the seventh paragraph on p. 713, the second sentence should read as follows: Early in training individual differences were great, but by the end of adaptation training, individual differences were quite small and all rats responded at close to asymptotic speeds.] A distinction between 2 classes of memory has been made in terms of the sensory availability of cues at the time of making discriminations that are influenced by past experience. Three tasks objectively defining this distinction were learned in a T-maze by 36 male Long-Evans rats in 3 groups: (a) a delayed non-matching-to-sample (DNMTS) that depended on representational memory; (b) a simple sensory discrimination (SD) that depended on dispositional memory; and (c) a more difficult discrimination that also depended on dispositional memory, called the simultaneous conditional discrimination (SCD). The DNMTS and SD tasks were acquired quickly; the SCD task took many more trials. Posterior septal lesions impaired DNMTS performance but had no effect on retention of tasks that depended on dispositional memory. Results indicate that dispositional and representational memory systems have at least partially distinct anatomical substrates in the brain and that it is the representational and not the conditional aspects of the DNMTS task that are impaired by the septal lesions. (21 ref) (PsycINFO Database Record (c) 2010 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.     

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)     

Age-related deficits on the radial maze and in fear conditioning: hippocampal processing and consolidation

Young adult, middle-aged, and old male F-344 rats were assessed for their hippocampal ability. This was accomplished by examining the animals on two different paradigms, each incorporating a simultaneous measure of hippocampal-dependent and -independent processing. The animals were fear conditioned and then tested for retention of the conditioning context and tone. This was followed by an 8-arm radial maze task which combined spatial working and cued reference memory elements. The two paradigms are compared in terms of task demands, potential confounds, and validity for aging studies. The results indicate that the performance of the animals on the two tasks is correlated. Age-related deficits limited to the hippocampal aspects of the above tasks were found, with no deficits found in the analogous but hippocampus-independent aspects of these tasks. The function of the hippocampus in incorporating new memories is time-related. Therefore, the possibility of age-related changes in consolidation was examined. It has previously been shown on the fear conditioning paradigm that the hippocampus is involved in retention of the aversive context for approximately 28 days. In the present study, an attempt was made to test the animals for retention of the conditioning context both early into the period of consolidation (10 days) and after consolidation should have been completed (52 days). The results indicate that, initially, the old animals show comparable retention to young rats. When examined later, young animals showed a stronger retention of the conditioning context than they had previously. The aged rats, however, did not seem to benefit from this additional period of time and in fact showed a decrease in retention of the conditioning context. The data are interpreted in terms of consolidation, alternative explanations of the data are presented, and suggestions are given for future research. Finally, the implications of such age-related changes in hippocampal consolidation on learning and memory are discussed.