Working Memory In Rats Research Articles

P-19-23 - Distribution of glial fibrillary acidic protein in the cochlear nucleus of adult and aged rats

The validity of delayed-matching-to-sample (DMTS) and related tasks executed in skinner boxes as an animal model for human working memory (WM) is confounded by the occurrence of mediating behaviour during delays. True matching, a supplementary task during delays and response similarity are ways to deal with this problem. However, until now rats have not been able to learn a true matching task in Skinner boxes and introduction of a supplementary task during delays does not sufficiently prevent mediating behaviour. Response similarity, on the other hand, effectively prevents the use of mediating behaviour by reducing the discriminative value of the behaviour during delays. Furthermore, it is argued that the interpretation of drug effects is confounded by baseline performance and mediating behaviour. It is shown that high baseline levels and high amounts of mediating behaviour can induce delay dependent drug effects, suggesting a specific effect on WM. We therefore assert that examination of delay-dependency of a drug effect alone is not sufficient to claim specific effects of a drug on WM. The delayed-conditional-discrimination (DCD) task uses response similarity to effectively reduce mediating behavior and does not generate high levels of baseline performance. The DCD task is therefore preferred over other tasks for the measurement of WM in rats using Skinner boxes.

Beta-amyloid(1–40) effects on behavior and memory

Beta amyloid 1–40 is a primary protein in plaques found in the brains of patients with Alzheimer's disease. There is evidence that unaggregated soluble β-amyloid may be neurotoxic and may have behavioral effects on some types of memory. In the current study, the 1–40 fragment of β-amyloid protein (βA4), or vehicle, was bilaterally injected into the rostral hippocampus of rats performing under stable food-maintained schedules of reinforcement or under a delayed conditional discrimination procedure. Under the first procedure, rats were trained to stability under a multiple fixed interval 15 s, fixed ratio 30 reinforcement schedule. This reinforcement schedule has proven sensitive to low-dose drug effects. Acute bilateral hippocampal βA4 (1.0, 2.0 and 3.0 μl of 10 −3 M) administration did not significantly alter responding, compared to vehicle, under either reinforcement condition. Following the acute single-injection regimen, rats were administered chronic daily βA4 (1μl of 10 −3 M), bilaterally, for 15 days. No significant changes in lever-pressing performance were observed during the chronic injection regimen, but performance declined significantly 30 days after termination of the chronic daily regimen. Histological examination revealed three of six rats showed showed positive reactions under Thioflavin S staining in and around the area of cannulae termination. The second assessment employed a delayed conditional discrimination procedure to evaluate the effects of intrahippocampal injections of βA4 on short-term working memory. This conditional discrimination procedure assesses appropriate responding, dependent on a previously presented stimulus, after delays of various lengths have been imposed between the stimulus and the response opportunity. Delay values ranged from 0.01 s to 20 s. Under this procedure, accuracy was unaffected across all delay values following single bilateral intrahippocampal injections of βA4 (1.0, 2.0 and 3.0 μl of 10 −3 M). Thus, the soluble unaggregated form of βA4, injected into the dorsal hippocampus, does not appear to have behavioral effects on performance or short-term working memory in rats, but multiple repeat injections produced performance decrements several weeks later. Repeated injection of βA4 through indwelling cannulae shows promise for development of an animal model of Alzheimer's disease.

Hippocampal and amygdaloid involvement in nonspatial and spatial working memory in rats: effects of delay and interference.

Parametric manipulations of the task demand were used to examine the role of the hippocampus and amygdala in nonspatial and spatial working memory in rats. Hippocampal lesions produced an immediate and long-lasting impairment of nonspatial working memory in an operant task. The memory deficits increased as the delay interval and the amount of proactive interference increased. Hippocampal lesions severely impaired spatial working memory in spatial alternation. Extensive postoperative testing reduced the magnitude of impairment of nonspatial but not spatial working memory. Amygdaloid lesions did not impair any aspect of performance in 2 tasks. The results suggest that the hippocampus, but not the amygdala, is involved in working memory and the task demand is a critical determinant for observing impairments of nonspatial working memory following hippocampal lesions.

Hippocampal and amygdaloid involvement in nonspatial and spatial working memory in rats: Effects of delay and interference.

Hippocampal and amygdaloid involvement in nonspatial and spatial working memory in rats: Effects of delay and interference.

Peony and its major constituent, paeoniflorin, improved radial maze performance impaired by scopolamine in rats

A traditional Chinese medicine, Shimotsu-to has been shown to improve spatial working memory in rats. Shimotsu-to consists of four herbs, Japanese angelica root, cnidium rhizome, peony root, and rehmannia root. In the present study, the effects of aqueous extracts of each component herb on scopolamine (0.3 mg/kg)-induced spatial working memory disruption were examined using an eight-arm radial maze task in rats. Among the four component herbs, peony root extract (0.25 and 1 g dried herb/kg, PO) exhibited the most potent antagonizing effect on the scopolamine disruption of the choice accuracy. Japanese angelica root extract ( 1 g dried herb/kg, PO) also significantly attenuated the scopolamine disruption, whereas neither cnidium rhizome nor rehmannia root affected it. Paeniflorin (0.01–1 mg/kg, PO), a major constitutent of peony root, dose-dependently attenuated the scopolamine-induced impairment in the choice accuracy. Scopolamine (0.3 mg/kg, IP) significantly decreased the acetylcholine contents in the hippocampus, cortex, and striatum. Although paeoniflorin alone did not affect the acetylcholine content decrease in the acetylcholine content in the striatum, but not in the hippocampus or cortex. These data suggest that peony root mainly contributes to the cognitive enhancing effect of Shimotsu-to and that paeoniflorin may be one of the active constituents of peony root.

Panax ginseng extract improves scopolamine‐induced deficits in working memory performance in the T‐maze delayed alternation task in rats

AbstractThe effects of Panax ginseng water extract on spatial working memory disruption induced by scopolamine were examined using a T‐maze delayed alternation task in rats. Scopolamine (0.025–0.1 mg/kg, i.p.) dose‐dependently impaired the maze performance, and physostigmine (0.4 mg/kg) significantly reversed the scopolamine (0.1 mg/kg)‐induced performance deficits. Ginseng extract (0.5–4.0 g dried root/kg) orally administered 60 min before testing dose‐dependently improved the maze performance disrupted by scopolamine (0.1 mg/kg). Ginseng extract given for 7 days in drinking water (2.0 and 4.0 g/kg/day) also exhibited dose‐dependent reversal of the scopolamine‐induced performance deficits. These data indicate the beneficial effects of ginseng extract on spatial working memory in rats.

Selective fimbria and thalamic lesions differentially impair forms of working memory in rats

Several series of experiments were designed to compare the effects of selective lesions of the fimbria or of thalamic nuclei on three different tasks involving working memory in rats: object recognition, place recognition, and the radial arm maze test. The main effects of fimbria lesions were as follows: they produced deficits in the radial maze; object recognition was spared or even facilitated, whereas place recognition was impaired. Electrolytic lesions of either centromedian-parafascicularis (CM-Pf) or dorsomedialis (DM) nuclei produced highly significant deficits in the radial maze test but spared object and place recognition. Ibotenate lesions of the CM-Pf had no effect on any test, which means that the critical structure in the effects of the electrolytic lesions of the CM-Pf was the fasciculus retroflexus (FR). These data may contribute two main points to animal models of hippocampal and thalamic amnesia: (1) different forms of working memory in rats might have different neural bases and (2) the FR may be involved in learning and memory processes.

The competitive NMDA antagonist AP5, but not the non-competitive antagonist MK801, induces a delay-related impairment in spatial working memory in rats

Rats were trained to alternate responses on a discrete trial working memory task on a T-maze. In Experiment 1, the rats were then matched for choice accuracy and allocated to three treatment groups. These were: implantation of osmotic minipumps for intraventricular infusion of either (a) 15 mM D-2-amino-5-phosphonopentanoic acid (AP5) or (b) artificial cerebrospinal fluid (VEH); and an unoperated control group (UNOP). In Phase 1 we assessed alternation performance with a minimal delay between responses: the UNOP and VEH rats continued to choose accurately; the AP5 rats showed an impairment of choice accuracy, but recovered over days. In Phase 2 a 20-s delay between responses was enforced, and choice accuracy was assessed following injections either of saline or of Milacemide HCl (10 mg/kg). There was now a severe and enduring impairment of choice accuracy in the AP5 group, but Milacemide injections did not affect performance in any of the treatment groups. In Experiment 2 rats were trained in a similar way, and then given intraperitoneal injections of MK801 or of physiological saline in a within-subjects design and tested for T-maze performance with a minimal or a 20-s delay between responses. In the first Phase, MK801 was given 10-min before behavioural testing commenced; in the second Phase, it was given 28-40 min before behavioural testing commenced. The outcome depended critically on the time between drug injection and testing. There was a significant drug-induced impairment of choice accuracy in both Phases; but in Phase 1 there was no impairment in testing with a minimal retention interval and an impairment with a 20-s retention both retention intervals. We conclude that AP5, but not MK801, interferes with temporary memory storage in a delay-dependent manner.

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 s to 20 or 60 s, 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 s 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.

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

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

P-74 - Effects of amiridin and tetrahydroaminoacridine (TUA) upon impaired working memory in rats

P-74 - Effects of amiridin and tetrahydroaminoacridine (TUA) upon impaired working memory in rats

Reference and working memory of rats following hippocampal damage induced by transient forebrain ischemia

Acquisition of reference and working memory was evaluated in an animal model of cerebral ischemia. Rats were subjected to 30 minutes of transient forebrain ischemia, allowed to recover, and then tested for 95 trials on an 8-arm maze with 5 arms baited. During the 95 trials post ischemic (PI) rats made significantly more working and reference errors than control ( p<0.05). However, an analysis of the last 20 trials (75–95) showed that while PI rats and control rats had comparable reference memory ( p>0.8). PI rats tended to have a persistent working memory deficit compared to controls ( p<0.06). Subsequent morphologic analysis showed that PI rats had almost complete loss of pyramidal neurons in the anterior CA1 region of the hippocampus, moderate to severe loss in mid-dorsal posterior hippocampus, and less damage to the dorsolateral striatum. These results suggest that the PI animal is a reasonable model for the permanent behavioral impairment and pathologic damage found in some human survivors of cardiac arrest.

Spatial working memory in rats: Effects of monoaminergic antagonists

To assess the possible involvement of the monoaminergic neurotransmitters norepinephrine, dopamine and serotonin in the maintenance of spatial working memory rats were treated with antagonists 0 or 2 hr after completing the first 4 choices in an 8 arm maze. Haloperidol (0.25–1 mg/kg), when administered 2 hr after Choice 4, produced a small but consistent impairment in performance on retention tests given 5 hr after the first 4 choices. This deficit closely resembled natural forgetting in terms of the type of errors committed. By contrast, haloperidol in the same doses given 0 hr after Choice 4 or 3 hr before the first 4 choices did not affect retention. Likewise treatment with propranolol (10–20 mg/kg), phentolamine (5–20 mg/kg) or methysergide (5–15 mg/kg) did not impair spatial memory, regardless of when these drugs were injected within the session. Evidently dopaminergic neuronal systems are important in the maintenance of normal spatial working memory.

A multiple choice apparatus for electrophysiological investigations of spatial working memory in rats

A multiple choice apparatus, minimizing the rat's movements and thus simplifying brain stimulation and/or recording in working memory experiments, consists of a dodecagonal enclosure (30 cm diameter, 100 cm high) with a horizontal platform assuming either an upper or a lower position, 43 or 65 cm below the top of the wall, respectively. The platform is moved between these two levels by a pneumatic system controlled by solid-state programming circuits. Each wall segment contains a choice window, 7 cm above the upper floor level, providing access to a recessed feeder. When the platform with a food-deprived rat moves into the upper position, the animal opens the hinged shutter of one window and gets the pellet. Five seconds later, a self-locking relay marks the visited window and the floor descends to the low position where it remains for a predetermined interval (e.g. 20 s), until it is raised again. The above cycle repeats as a long as different windows are chosen. When a choice is directed to an already visited window (error), the floor returns to the low position at once. During one trial, the animal is allowed 12 choices and the number of errors (i.e. choices directed to already entered windows) is recorded. In spite of the great reduction of kinaesthetic and vestibular signals and the almost complete elimination of visual extramaze cues, the working memory performance is similar to that in analogous radial maze.

Scopolamine does not disrupt spatial working memory in rats

The importance of cholinergic systems for spatial working memory was examined by injecting scopolamine at varying times during a 5 hr-long retention interval imposed between the rat's fourth and fifth choices in an 8 arm maze. Regardless of whether or not the testing procedure required the rats to adopt a spatial solution for the task, scopolamine (1.0–5.0 mg/kg) did not impair retention in a manner that was suggestive of an effect on working memory. Modest deficits observed in some conditions appeared to result from drug effects on performance. Previous findings of impaired acquisition of accurate spatial behavior by scopolamine-treated rats evidently reflect an influence of the drug on physiological systems other than those necessary to maintain working memory for spatial information.