Involvement of Ventral Pallidum in Prefrontal Cortex-Dependent Aspects of Spatial Working Memory.

Ventral pallidum (VP) is an important source of limbic input to medial thalamus. Three studies examined the role of VP in spatial memory tasks impaired by medial thalamic lesions. In the 1st study, rats with VP lesions were impaired performing delayed matching trained with retractable levers (DMRL), a measure sensitive to prefrontal (but not hippocampal) damage. The 2nd study demonstrated dose-dependent DMRL impairment following microinjection of gamma-aminobutyric acidA, glutamate, or mu-opioid agonists in VP. In the 3rd study, VP lesions had no effect on varying choice radial-maze delayed nonmatching, a measure sensitive to hippocampal (but not prefrontal) lesions. These results suggest a common role in spatial memory for VP and other components of prefrontal-ventral striatopallidothalamic circuits distinct from hippocampal function. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Selective immunotoxic lesions of basal forebrain cholinergic cells: Effects on learning and memory in rats.

Male Long-Evans rats were given injections of either 192 IgG-saporin, an apparently selective toxin for basal forebrain cholinergic neurons (LES), or vehicle (CON) into either the medial septum and vertical limb of the diagonal band (MS/VDB) or bilaterally into the nucleus basalis magnocellularis and substantia innominata (nBM/SI). Place discrimination in the Morris water maze assessed spatial learning, and a trial-unique matching-to-place task in the water maze assessed memory for place information over varying delays. MS/VDB-LES and nBM/SI-LES rats were not impaired relative to CON rats in acquisition of the place discrimination, but were mildly impaired relative to CON rats in performance of the memory task even at the shortest delay, suggesting a nonmnemonic deficit. These results contrast with effects of less selective lesions, which have been taken to support a role for basal forebrain cholinergic neurons in learning and memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of hippocampal and parietal cortex lesions on memory for egocentric distance and spatial location information in rats

To assess the working memory system for egocentric distance and place information, delayed matching-to-sample (DMTS) go/no-go tasks were run for each rat. To assess the reference memory system, and to serve as a control for nonmemory deficits, successive discrimination go/no-go tasks were then conducted using the same rats. Rats with hippocampal, but not parietal cortex, lesions were impaired relative to controls in the working memory (DMTS) task for both egocentric distance and place information, although the deficit observed in the working memory task for egocentric distance information by rats with hippocampal lesions was mild. Neither hippocampal nor parietal cortex lesioned rats were impaired relative to controls in the reference memory (successive discrimination) task for either cue. The hippocampus appears to be involved in working memory for egocentric distance and in spatial location information, whereas the parietal cortex is not.     

Lesions of rat perirhinal cortex exacerbate the memory deficit observed following damage to the fimbria-fornix.

Rats that had received bilateral lesions of the perirhinal cortex, fimbria-fornix, combined lesions of both these structures, or sham operations were tested on an object-guided delayed non-match-to-sample task. Perirhinal lesioned and fimbria-fornix lesioned rats were moderately impaired when delay intervals of 30 s or more were introduced between the sample and test phases of the experiment. Animals with combined lesions displayed a considerably greater impairment than animals with lesions of either structure alone. The combined lesioned animals were severely impaired in the initial acquisition of the task and displayed a profound memory deficit at delay intervals of greater than 4 s. These results emphasize the importance of the perirhinal cortex to memory function and suggest that the perirhinal cortex and the hippocampal formation may function interactively in the execution of memory processes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pilocarpine and physostigmine attenuate spatial memory impairments produced by lesions of the nucleus basalis magnocellularis.

Three experiments, with 63 male Long-Evans rats, investigated the effects of bilateral ibotenic acid-induced lesions of the nucleus basalis magnocellularis (NBM) on the acquisition and retention of several spatial memory tasks. Maintenance of spatial memory in a food-search task was impaired following NBM lesions. Acquisition of spontaneous alternation and reinforced alternation in a T-maze, but not the acquisition of a position habit, was also significantly impaired in Ss with these lesions. In several of the tasks, there was evidence of some learning in the lesioned Ss after substantial training, although they were significantly deficient when compared with controls. Intraperitoneal administration of the cholinergic agonists physostigmine sulfate (0.5 mg/kg) or pilocarpine nitrate (3 mg/kg) prior to behavioral testing resulted in a rapid and significant improvement in the performance of the lesioned Ss. Lesions significantly reduced the activity of choline acetyltransferase in the anterior and the posterior neocortex but not the hippocampus. Results indicate that the cholinergic projections originating in the NBM are involved in the learning and memory of spatial tasks. (48 ref) (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.     

Disconnection of the amygdala central nucleus and substantia innominata/nucleus basalis disrupts increments in conditioned stimulus processing in rats.

Rats with a neurotoxic lesion of the amygdala central nucleus (CN) in one hemisphere and a 192 immunoglobulin G (192IgG)-saporin lesion of cholinergic neurons in the contralateral substantia innominata/nucleus basalis (SI/nBM) failed to show the enhanced attentional processing of a conditioned stimulus (CS) observed in sham-operated rats when that CS's predictive value was altered. Performance of these asymmetrically lesioned rats was poorer than that of rats with a unilateral lesion of either structure or with a symmetrical lesion of both structures in the same hemisphere. These results implicate connections between the CN and SI/nBM in the incremental attentional processing of CSs, extending previous research that has shown similar effects of bilateral lesions of either the CN or the SI/nBM. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Visual experience, unilateral cortical lesions, and lateralization of function in rats.

Measured the effects of early visual experience and later unilateral neocortical lesions on the behavior of 30 male hooded Long-Evans rats in an open-field, 17-arm spatial maze and on a visual field or perimetry test. 30 Ss were formed into 6 groups—3 light-reared (LR) and 3 dark-reared (DR)—of 5 Ss each in order to receive right-, left-hemisphere, or sham neocortical lesions. The comparison of behavior observed in the open field revealed that LR Ss with right-hemispheric lesions were more active and reared more than any of the other Ss. On the radial-maze task, in which 8 of 17 arms were baited, all Ss with lesions performed less effectively than did sham-operated Ss. The effect of the lesions was significantly greater for LR than for DR Ss. Perimetry testing revealed that, although the lesioned Ss did react to stimuli throughout their visual field, some contralateral neglect was evident in both LR and DR Ss; the lesions had a greater impact on orientation behavior of LR Ss, however. No evidence emerged of any functional asymmetry following the unilateral cortical lesions. Findings are discussed in terms of V. H. Denenberg's (1981) hypothesis about cerebral and functional asymmetry in the rat. (37 ref) (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)     

Unilateral labyrinthectomy downregulates glutamate receptor delta-2 expression in the rat vestibulocerebellum

Subcortical damage in neonates often has more severe consequences than in adults. Unilateral electrolytic hippocampal lesions in adult rats typically result in transient memory deficits, whereas neonatal lesions cause lasting memory impairments. We hypothesized that unilateral lesions made at birth may affect synaptic physiology in the contralateral hippocampus. Consequently, the ability to sustain long-term potentiation (LTP), a form of synaptic plasticity believed to underlie certain forms of memory, was compared between slices from the remaining hippocampus of rats lesioned as newborns and as adults. Initial studies showed that a train of 10 stimulation bursts patterned after the hippocampal theta rhythm produced robust and stable LTP both in slices from controls and rats lesioned at birth. However, a theta burst pattern of stimulation closer to intrinsic physiology (five burst pairs separated by 30 s each), induced significantly less LTP in slices from rats lesioned at birth compared to those from controls and rats lesioned as adults. To investigate possible mechanisms underlying the deficit, the degree of paired-pulse facilitation (PPF) as well as the amount of depolarization occurring between two successive theta bursts were analyzed. The lesion did not detectably change PPF characteristics, suggesting that presynaptic mechanisms are normal. However, the extent to which a burst response was increased by a prior burst was significantly diminished in slices from rats lesioned at birth compared to those from controls and rats lesioned as adults, indicating that postsynaptic factors involved in the initial triggering events of LTP are affected by the lesion. Reduced ability to sustain LTP in the remaining hippocampus may contribute to impaired memory function after unilateral neonatal hippocampal lesion.     

Effect of cholinesterase inhibitors on Morris water task behavior following lesions of the nucleus basalis magnocellularis.

The effect of bilateral nucleus basalis magnocellularis (nBM) lesions on performance in the Morris water task was examined in the rat, and the ability of anticholinesterase inhibitors to reverse the behavioral deficit was evaluated. Lesions of nBM resulted in a prolongation of escape latency. A spatial probe trial revealed that sham-lesioned Ss swam a greater percentage of the distance in the platform quadrant; this finding was abolished by nBM lesions. Lesions of nBM produced a nonsignificant increase in both open-field activity and activity-box scores. In Exp 1, administration of physostigmine on Day 3 resulted only in a decrease in escape latency. In Exp 2, in which cholinesterase inhibitors were administered daily for 5 days, 0.32 mg/kg but not low-dose physostigmine or 2 substituted N,N-alkyl phenyl carbamate cholinesterase inhibitors improved escape latency on Day 3. It is concluded that nBM lesions impair behavior on the Morris water task and physostigmine shortens escape latency. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

EGG phosphatidylcholine combined with vitamin B12 improved memory impairment following lesioning of nucleus basalis in rats

We investigated the effects of egg phosphatidylcholine (PC) combined with vitamin B12 on memory in the Morris water maze task, and on choline and acetylcholine (ACh) concentrations in the brain of rats. Animals with nucleus basalis Magnocellularis (NBM) lesion received intragastric administration of egg PC or vitamin B12, or both for 18 days. Memory acquisition and retention were remarkably impaired in NBM lesioned rats compared with in sham-operated control. NBM lesioned group had lower choline and ACh concentrations than control group in the frontal cortex. High dose of egg PC alone significantly increased choline concentration, but did not change ACh concentration in the frontal cortex. High dose of vitamin B12 alone did not change choline and ACh concentrations in the brain. Either egg PC or vitamin B12 did not improve memory acquisition and retention. However, low dose of egg PC combined with vitamin B12 significantly increased ACh concentration and improved memory acquisition and retention in the NBM lesioned rats. We concluded that egg PC combined with vitamin B12 improved the memory impairment of NBM lesioned rats through the action on the cholinergic neurons.     

Promoter/repressor system of Lactobacillus plantarum phage og1e: characterization of the promoters pR49-pR-pL and overproduction of the cro-like protein cng in Escherichia coli

Previous studies have shown that extensive damage to the medial prefrontal cortex (mPFC) of rats causes reversal learning deficits. The mPFC of rats, however, consists of several subareas that are different from each other in both cytoarchitecture and neural connectivity, suggesting a functional dissociation among the mPFC subareas. In the present study, selective lesions of the mPFC of rats were made with a specially designed microknife whose intracranial placement could be controlled stereotaxically. Restricted lesions were made to each of the 3 parts of the mPFC: the anterior cingulate area (AC) (including the medial precentral area, PrCm), the prelimbic area (PL), and the infralimbic area (IL). One week after surgery, rats were trained in an aversively motivated visual discrimination task in a novel rotating T-maze. After reaching the acquisition criterion, rats were trained in a reversal task in the same maze. No difference was found in acquisition between control and mPFC lesioned rats. However, lesions of either the PL or the IL produced a marked deficit in the reversal task. This behavioral deficit was not found in rats with lesions of the AC. The results indicate that the mPFC of rats is not essential for discrimination learning, but that each of the 2 ventral subareas of the mPFC, PL, and IL, plays a critical role in reversal learning.     

Clonal origin of toxic thyroid nodules with constitutively activating thyrotropin receptor mutations

The effects of intraventricular administration of ethylcholine aziridinium ion (AF64A) were studied in male Wistar rats. Bilateral injections of AF64A (3 nm/3 mcl) reduced the reactions to biological alarm signal and produced a decrease in the open-field activity 3 weeks after this lesion. The lesioned rats also displayed deficit in retention of a passive avoidance task.     

Post-traumatic survival and recovery of the auditory sensory cells in culture

The effects of hippocampal and lateral septum lesions were compared in rats tested in a water maze spatial memory task, and the effect of chlordiazepoxide (CDP) was examined. There was a significant interaction for lesion and CDP in the septal lesioned subjects, with the lesioned animals performing worse than control animals, and CDP improving the performance of lesioned animals. CDP had no effect on impaired performance in hippocampal lesioned animals.     

Dynorphin A-(1-13) attenuates basal forebrain-lesion-induced amnesia in rats

The effects of dynorphin A-(1-13), an endogenous kappa opioid agonist, on basal forebrain (BF)-lesion-induced amnesia in rats were investigated using step-through-type passive avoidance task. The BF was lesioned by injecting the cholinergic neurotoxin ibotenic acid (6 micrograms/side). The number of rats achieving the cut-off time (600 s) of step-through latency (STL) in BF-lesioned group significantly decreased as compared with that in sham-operated group. Dynorphin A-(1-13) (0.3 micrograms) significantly increased the number of rats achieving the cut-off time of STL in BF-lesioned rats. These results suggest that dynorphins play an improving role in the impairment of memory processes in BF-lesioned rats.     

Entorhinal-perirhinal lesions impair performance of rats on two versions of place learning in the Morris water maze.

The effects of entorhinal–perirhinal lesions in rats were studied with 2 versions of a place learning task in the Morris water maze. These lesions impaired performance on a multiple-trial task (3 days of 6 trials and a probe trial). This assessment was followed by a task in which rats were repeatedly trained to find novel locations with a variable delay (30 sec or 5 min) imposed between each sample trial and retention test. Entorhinal–perirhinal damage produced a delay-dependent deficit in spatial memory: Rats with lesions were impaired at the 5-min delay relative to the control group and to their own performance at 30 sec. These findings are discussed in relationship to memory impairment after entorhinal damage and spatial learning deficits observed after hippocampal damage. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lymphomas of the urinary tract

Lesioning the ventral hippocampus of neonatal rats has been proposed as an experimental model of schizophrenia. This lesion causes a syndrome of hyperresponsivity to the stimulant effects of amphetamine, impaired grooming and disrupted social interactions, effects that emerge during adolescence, much like schizophrenia. Persisting cognitive effects of neonatal ventral hippocampal lesions were assessed in the current study, because the hippocampus is critically important for a variety of cognitive functions and cognitive impairment and because it is an important feature of schizophrenia. Spatial learning and working memory were assessed in the radial-arm maze, which is sensitive to the adverse effects of hippocampal lesions made in adults. Lesioned rats showed pronounced deficits in radial-arm maze choice accuracy that persisted throughout training. Deficits were seen during the prepubertal period as well as in adulthood. Even though the lesioned rats performed more poorly, they were significantly less sensitive to the amnestic effects of the nicotinic antagonist mecamylamine and the muscarinic antagonist scopolamine. No significant effects of nicotine or amphetamine were seen in either the lesioned or control groups. The long-lasting deficits in spatial learning and working memory resulting from neonatal ventral hippocampal lesions show that, unlike frontal cortical lesions during the same age, the effects of hippocampal lesions are not overcome during development. The resistance to the amnestic effects of nicotinic and muscarinic acetylcholine (ACh) antagonists suggests that the hippocampus is a critical site for the action of these drugs. Neonatal hippocampal lesions may provide a good model of the cognitive impairments of schizophrenia and may be useful to assess novel drug effects to counteract the cognitive deficits in schizophrenia.     

"Differential involvement of the dorsal anterior cingulate and prelimbic-infralimbic areas of the rodent prefrontal cortex in spatial working memory": Correction to Ragozzino et al. (1998).

Reports an error in "Differential involvement of the dorsal anterior cingulate and prelimbic-infralimbic areas of the rodent prefrontal cortex in spatial working memory" by Michael E. Ragozzino, Spencer Adams and Raymond P. Kesner (Behavioral Neuroscience, 1998[Apr], Vol 112[2], 293-303). Figure 1 (page 295) and Figure 4 (page 299) were printed incorrectly. The corrected figure pages and corresponding captions are provided in the erratum. (The following abstract of the original article appeared in record 1998-01023-003.) The present study examined the effects of quinolinic acid lesions of the dorsal anterior cingulate and prelimbic-infralimbic cortices on spatial working memory and spatial discrimination using go/no-go procedures. All testing occurred in a 12-arm radial maze. In a working memory task, rats were allowed to enter 12 arms for a cereal reward. Three or 4 arms were presented for a 2nd time in a session, which did not result in a reward. In a spatial discrimination task, rats had successive access to 2 different arms. One arm always contained a reward, and the other never contained a reward. Prelimbic-infralimbic lesions impaired spatial working memory but only produced a transient spatial discrimination deficit. Dorsal anterior cingulate lesions did not induce a deficit in either task. These findings suggest that the prelimbic-infralimbic cortices, but not the anterior cingulate cortex, are important in spatial working memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Simulation exercises, a problem oriented method of learning public health in medical education]

Spontaneous and amphetamine-elicited locomotor activity in rats is reduced by most clinically effective antipsychotic drugs. We have recently demonstrated that intracerebroventricular infusion of kainic acid (KA), which produces cell loss in the hippocampus and other limbic-cortical brain regions, increases spontaneous and amphetamine-elicited locomotion. The present study determined if KA lesions alter the suppressive effects of the antipsychotic drugs, haloperidol and clozapine, on spontaneous and amphetamine-elicited locomotor behavior. Young adult male rats (70 days of age) received intracerebroventricular infusions of vehicle or KA, which produced hippocampal pyramidal cell loss in each rat and more variable cell loss or gliosis in the amygdala, piriform cortex, and laterodorsal thalamus. Thirty days post-surgery, lesioned and control rats were tested once a week for locomotor responses to drug treatments. As observed previously, spontaneous locomotor activity and hyperactivity elicited by amphetamine (1.50 mg/kg s.c.) were greater in lesioned animals than controls. In addition, the level of spontaneous activity and/or amphetamine-elicited hyperlocomotion observed in lesioned rats after haloperidol treatment (0.13, 0.35, or 1.50 mg/kg s.c.) was greater than that found in controls. Locomotor responses to low (6.30 mg/kg) and moderate doses of clozapine (20 mg/kg) were similar in lesioned and control rats, although lesioned rats were more active than controls following the administration of a high dose of clozapine (30 mg/kg). These data indicate that the hyperactivity associated with limbic-cortical lesions may be insensitive to reversal by haloperidol, yet uniquely sensitive to suppression by clozapine.