Mediodorsal thalamic lesions impair radial maze performance in the rat.

The role of the mediodorsal thalamic nucleus (MD) in spatial memory processes was assessed. Animals were preoperatively trained on an 8-arm maze placed in a visually deprived environment. Following 50 acquisition trials, one group received bilateral electrolytic lesion of the MD thalamus, whereas the other group received sham lesions. On postoperative tests of radial maze performance, MD lesioned animals made significantly more errors, made more errors sooner, and emitted fewer correct responses before making an error than did sham controls. The lesioned subjects also exhibited considerable perseveration immediately postoperation and developed response patterning on postlesion trials. Lesions of the mediodorsal thalamus may fundamentally compromise memory systems and alter ability to respond appropriately in a minimally cued environment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Within-subject decline in delayed-non-match-to-sample radial arm maze performance in aging Sprague-Dawley rats.

A within-subject design was used to examine delayed-non-match-to-sample radial arm maze performance in aging (6–18 months) male Sprague-Dawley rats. A decrease in correct choices and an increase in retroactive errors were observed at all retention intervals at 18 months of age compared with performance at 6 or 12 months. No age by retention interval interaction was observed. Neither age nor increasing retention interval influenced proactive errors during the retention test. The observation of an age- and delay-dependent increase in retroactive errors, but not proactive errors, suggests that the deficit relates to a memory dysfunction as opposed to a generalized performance deficit. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Physostigmine, but not 3,4-diaminopyridine, improves radial maze performance in memory-impaired rats

The results of some studies suggest that 3,4-diaminopyridine (3,4-DAP), a drug that enhances the release of acetylcholine, may improve memory. The present study examined the ability of 3,4-DAP to reverse the memory impairment produced by scopolamine and the ability of 3,4-DAP and physostigmine to reverse the memory impairment produced by quinolinic acid lesions of the nucleus basalis magnocellularis (nbm) in rats. Mnemonic functioning was assessed with the use of a partially baited eight-arm radial maze. Entries into arms that were never baited were defined as reference memory errors; entries into baited arms from which the food already had been eaten were defined as working memory errors. In Experiment 1, 0.1 mg/kg scopolamine produced a significant increase in working and reference memory errors. Various doses of 3,4-DAP had no significant ameliorative effect on the mnemonic deficit. In Experiment 2, cholinergic function was impaired using a unilateral intra-nbm injection of quinolinic acid (120 nmol in 1.0 microliter). These lesions reduced the levels of the cholinergic marker, choline acetyltransferase, in the cortex by more than 40%. Results showed that the nbm lesion animals were significantly more impaired on the working than reference memory component of the task. Physostigmine (0.01, 0.05, 0.10, 0.20, 0.50 mg/kg) dose-dependently decreased the number of working but not reference memory errors. 3,4-DAP (10(-8), 10(-6), 10(-4), 10(-2), 10(0) mg/kg) had no reliable effect. It was concluded that physostigmine, but not 3,4-DAP, ameliorates memory impairments following decreases in cholinergic function.     

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)     

The effect of excitotoxic lesions centered on the perirhinal cortex in two versions of the radial arm maze task.

Rats with bilateral ibotenic acid lesions centered on the perirhinal cortex and sham-operated controls were tested in 2 versions of a spatially guided radial arm maze task. Lesioned rats made significantly more errors and required more sessions to reach criterion relative to controls in the standard radial maze task. When they were tested in a delayed nonmatch to sample version of this task, lesioned rats made more errors during the predelay phase and at both the 30-s and 10-min delays of the postdelay phase. These findings provide further support for the hypothesis that the role of the perirhinal cortex in object recognition memory may include reference to some spatial aspect of the environment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Selective memory impairments produced by transient lidocaine-induced lesions of the nucleus accumbens in rats.

Reversible lidocaine-induced lesions of the nucleus accumbens (NAC) impaired performance on the spatial win-stay, but not on the cued win-stay, radial arm maze task. Pretraining lesions on the former task did not affect foraging for 4 pellets during either the training or test phases. In contrast, lesions given prior to the test phase significantly disrupted retrieval of 4 pellets on the 8-arm maze. Comparable deficits also were observed in rats trained to forage for 4 pellets on an 8-arm maze without prior win-shift experience. State-dependent drug effects were ruled out by replicating the disruptive effects of lidocaine infusions into the NAC on spatial win-shift performance in rats receiving this treatment prior to both training and test phases. These results suggest that the NAC may interact with the hippocampus to guide foraging behavior requiring memory of previous spatial locations on a maze. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Extinction-induced spatial dispersion in the radial arm maze: Arrest by ethanol.

Investigated adaptive changes in response to extinction by making provisions that permitted behavior to shift away from trained routine. The baiting of 4 arms in an 8-arm radial maze increasingly restricted movements by 32 male Sprague-Dawley rats to those arms: The unbaited arms afforded a new direction for behavior to take during extinction. Withdrawal of reward was followed by an immediate and active expansion of visited sites, and previously unrewarded arms were regularly sampled. This was one consequence of extinction; the other was the decline in overall rate of arm entry, whether arms were previously baited or not. Ethanol (1.5 or 2.0 g/kg) eliminated the spatial dispersions attendant on nonreward but did not affect the decline in overall responsiveness. It is concluded that ethanol's deletion of extinction-induced spatial variability may account for its impairment on reversal and other kinds of tasks that require a shift away from old patterns of behavior. (23 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

3,4 Methylenedioxymethamphetamine (ecstasy) impairs eight-arm radial maze performance and arm entry pattern in rats.

The recreational use of 3,4 methylenedioxymethamphetamine (ecstasy) in humans has been associated with memory impairment. The present study examined whether ecstasy impairs short- and long-term working memory and the pattern of arm entries in rats tested in the 8-arm radial maze with a 2-hr delay. After completing the training session, the rats were given a single dose of ecstasy (1, 2, or 3 mg/kg ip) 20 min before the test. The highest dose slightly affected short-term working memory. Under conditions of delay, there was a progressive deficit in long-term working memory, starting from I mg/kg. Under both test conditions, 2 and 3 mg/kg flattened the pattern of arm entry. None of the doses caused hyperlocomotion or stereotypy in the radial maze. These findings suggest that acute ecstasy mainly affects the long-term components of working memory and disrupts the pattern of arm entry in a way similar to serotonergic agents. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of repeated disorientation on the acquisition of spatial tasks in rats: Dissociation between the appetitive radial arm maze and aversive water maze.

This study examined the effects of disorientation on the acquisition of different spatial reference memory tasks. In an appetitively motivated radial arm maze task in which 1 arm was consistently baited, rats that were disoriented before each trial were impaired in their ability to acquire the task relative to rats placed in a clear container and not disoriented. However, disoriented rats were able to learn a Morris water maze and a water version of the radial arm maze under similar training conditions, suggesting that the effects of disorientation may interact with the quality or quantity of motivation involved in a given task. These results suggest that appetitive and aversive spatial tasks are dissociable, and that any impairment that is due to disorientation is specific to the appetitive radial arm maze task. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Role of dentate gyrus cells in retention of a radial arm maze task and sensitivity of rats to cholinergic drugs.

Male rats that received bilateral injections of colchicine into 2 rostrocaudal sites showed relatively long-lasting alterations in a previously acquired radial arm maze task and specific destruction of dentate granule cells. Subsequent experiments with cholinergic drugs indicate that physostigmine or nicotine had no effect on number of errors made in the maze, although other signs of cholinergic or pharmacological activity were present. RS-86, an analog of arecoline, decreased errors in colchicine-treated Ss, but effects were associated with signs of parasympathetic overstimulation and behavioral sedation. Pretreatment with scopolamine increased errors in controls but had no effect in colchicine-treated Ss. Colchicine-treated Ss were less sensitive to the motor stimulant effect of scopolamine. Effects appeared to be associated with increased levels of choline acetyltransferase in the hippocampus and a down regulation of muscarinic postsynaptic receptors. Intradentate colchicine may destroy granule cells, leading to compensatory reinnervation of cholinergic nerve terminals having cell bodies in the septum. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Olfactory mechanisms in the control of maternal aggression, appetite, and fearfulness: Effects of lesions to olfactory receptors, mediodorsal thalamic nucleus, and insular prefrontal cortex.

During lactation the female rat is hyperphagic, aggressive toward adult conspecifics, and less fearful than usual. In the first experiment the importance of olfactory receptors was investigated by surgically removing the olfactory epithelium of the nasal cavity. Mother rats subjected to this treatment consumed significantly less food and weighed less than sham-operated females. Moreover, experimental subjects displayed a dramatic decrease in maternal aggression. Fear behavior (sound-elicited freezing), on the other hand, was not affected by the lesions. The mediodorsal thalamic nucleus and the prefrontal insular cortex form part of the central olfactory system. The second experiment assessed the involvement of this olfactory-related thalamocortical system on the behavioral profile of mother rats. It was found that whereas the thalamic and cortical lesions left food intake and fear behavior unaffected, they significantly decreased the frequency with which the mother would attack an intruder male placed into her home cage. The sense of smell appears, according to the present experimenters, to play a crucial role in maternal aggression. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

NMDA but not AMPA receptor antagonists impair the delay-interposed radial maze performance of rats

Long-term treatment of Parkinson's disease (PD) with levodopa is complicated by the development of motor fluctuations and dyskinesias. Posteroventral pallidotomy can improve tremor, bradykinesia, rigidity, and dyskinesias in PD. We performed chronic stimulation of the globus pallidus (CSGP) to duplicate the positive results of pallidotomy with reduced risk of permanent neurologic deficit in patients with advanced PD. The lead for CSGP was stereotactically implanted with the aid of microelectrode recordings in the globus pallidus pars interna. An electrical pulse generator was implanted in the subclavicular region. Stimulation settings were adjusted by computer. Five PD patients (four men, one woman) with disabling symptoms were enrolled. Three of the patients had bilateral implants. At 3 months following the last implant, four patients rated themselves as markedly improved, and one patient was moderately improved. The amount of time in the "on" state increased from 21% at baseline to 65% at 3-month follow-up (p < 0.05). There was a significant improvement in all subscales of the UPDRS (p < 0.05). One patient had an asymptomatic intracranial bleed, one patient had transient hemiparesis during surgery with stimulation, and one patient required surgical repositioning of the lead. Adverse effects caused by stimulation were minimal. CSGP is a safe and effective procedure in PD patients with motor fluctuations and dyskinesias.     

Thalamic amnesia reconsidered: Excitotoxic lesions of the intralaminar nuclei, but not the mediodorsal nucleus, disrupt place delayed matching-to-sample performance in rats (Rattus norvegicus).

Rats with large thalamic lesions affecting the mediodorsal (MDn) and intralaminar (ILn) nuclei are impaired performing delayed matching to sample tasks (DMTS). To determine the neurological basis of this deficit, we trained rats to perform a place DMTS task and then compared the effects of excitotoxic lesions of the MDn, the ILn, and the lateral internal medullary lamina (L-IML). The MDn lesion had little effect. The ILn group was significantly impaired throughout 8 months of training. The L-IML group exhibited an intermediate level of impairment. Varying the sample response requirement, retention intervals, and trial-to-trial congruence in the side reinforced, had predicted effects, as did variations in response latency. However, none of these factors interacted with the treatment effects. These findings indicate that DMTS performance is disrupted by lesions of the ILn but not the MDn. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Impairments in negative patterning, but not simple discrimination learning, in rats with 192 IgG-saporin lesions of the nucleus basalis magnocellularis.

Rats with 192 IgG-saporin lesions of the nucleus basalis magnocellularis (NBM) and sham-operated rats were trained in either a simple discrimination paradigm assessing simple association learning or a negative patterning paradigm assessing configural association learning. In the simple discrimination task, rats were reinforced for responding to a light but were not reinforced for responding to a tone. In the negative patterning discrimination task, rats were reinforced for responding to either a light or a tone presented alone but were not reinforced for responding to both stimuli presented simultaneously. Simple discrimination learning was not affected, whereas acquisition of negative patterning was impaired by NBM lesions. Impaired configural association learning may reflect a loss in the ability of rats with NBM lesions to attend to multiple sensory stimuli or to cope with conflicting response strategies. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Retrograde degeneration of thalamic neurons in the mediodorsal nucleus after neonatal and adult aspiration lesions of the medial prefrontal cortex in the rat. Implications for mechanisms of functional recovery

The behavioural consequences of neonatal lesions of the frontal cortex are limited as compared with similar lesions performed in adulthood. The present study has investigated, using unbiased quantitative methods with randomized systematic sampling, the total neuronal cell numbers in the mediodorsal nucleus of the thalamus after aspiration lesions of the medial prefrontal cortex performed in neonatal and in adult rats. It was found that the reduction in total cell numbers after neonatal prefrontal cortex lesions was similar to that found after adult cortex lesions. In neonatally lesioned animals the neuronal cell density was significantly increased by 13%, whereas in adult lesioned animals it was unchanged. On the other hand, the volume of the mediodorsal nucleus was reduced by 27% in neonatally, and 20% in adult lesioned animals. Total neuronal cell number of the mediodorsal nucleus was significantly decreased in neonatally as well as in adult lesioned rats, by 14% and 21%, respectively. These findings are discussed in the light of the previously proposed role of the thalamus as a neural substrate of functional sparing after neonatal cortical lesions.     

Cholinergic mediation of spatial memory in the preweanling rat: Application of the radial arm maze paradigm.

In 2 experiments with 70 Sprague-Dawley rats, Ss were trained and tested in the maze from 16 to 25 days of age. Results show that Ss that received training performed significantly better than those naive to the task and better than chance, which suggests an early capacity for this type of learning. To distinguish between the working and the reference memory components of the task, a modification of the basic radial arm maze paradigm was used. Ss trained from 16 days received drug injections of saline, methscopolamine bromide, scopolamine hydrobromide, or arecoline hydrobromide prior to testing at 25 days. Results indicate that central cholinergic antagonism severely impaired working memory while sparing reference memory. This finding is consistent with a role for acetylcholine in adult learning and memory, specifically in working memory. Findings document that (a) the radial-arm-maze paradigm can be used effectively for the developmental study of learning and memory in the rat and (b) cholinergic system(s) mediates working memory at an early age. (33 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Low levels of estradiol facilitate, whereas high levels of estradiol impair, working memory performance on the radial arm maze.

Previous investigations of estradiol's effects on learning and memory yielded equivocal results. This study was designed to determine whether these inconsistencies were due to dose-dependent effects of estradiol on different memory processes. Ovariectomized female rats were injected daily with estradiol benzoate (EB; 0.32, 1.00, or 5.00 μg) or vehicle. Approximately 3 hr after injection, rats were run on a hippocampus-dependent working/reference memory version of the radial arm maze. Total number of working (WME), reference, and combined working/reference memory errors were scored. Compared with vehicle, 1.00 or 5.00 μg EB (high physiological) impaired performance by increasing the number of WME, whereas 0.32 μg EB (low physiological) facilitated performance by decreasing the number of WME. Taken together, these data demonstrate a dose-dependent effect of EB on working memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Radial-arm maze behavior by rats with dorsal hippocampal lesions: Effects of cuing.

In 4 experiments with 180 male Wistar and Long-Evans rats, Ss with bilateral dorsal hippocampal lesions were impaired when tested on standard (noncued) versions of the radial-arm maze, but other hippocampal groups performed almost as well as cortical and operated control groups when salient visual cues were added to each arm. Preoperative training on the noncued, but not the cued, maze interfered with the benefits of postoperatively cuing hippocampal groups. Control groups performed equally well under all cuing and training conditions. Procedures that eliminated response sequencing did not affect performance of hippocampal or control groups. Results are interpreted as reflecting hippocampal involvement in mediating spatial cues, but not necessarily along the lines predicted by cognitive map theory. It is suggested that deficits of animals with hippocampal lesions represent 1 manifestation of a general impairment in processing information. (39 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Acquisition, retention, and extinction of operant discriminations in rats with nucleus basalis magnocellularis lesions.

Effects of bilateral ibotenic acid lesions of nucleus basalis magnocellularis (NBM) and scopolamine treatment on different aspects of learning and memory in an operant discrimination task were assessed. In Experiment 1, NBM lesions impaired acquisition performance. In Experiment 2, scopolamine lowered response rates but did not affect discrimination accuracy in lesioned or control rats. In Experiment 3, although pretrained rats showed transient increases in commission errors, percentage correct responding remained above chance levels after lesion. During extinction in Experiment 4, operant responding diminished more quickly in pretrained NBM-lesioned rats than in controls, but subsequent reacquisition performance was equivalent in both groups. Results suggest the NBM is importantly involved in discrimination learning, but cholinergic activity may be less critical for memory retention than for acquisition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)