Impaired delayed spatial win-shift behaviour on the eight arm radial maze following excitotoxic lesions of the medial prefrontal cortex in the rat

The delayed spatial win-shift (DSWS) radial maze task requires that animals hold spatial information for reward location "on-line" both during task performance and across a delay. Temporary lidocaine inactivation of anterior cingulate (AC) and prelimbic (PL) regions of the rat medial prefrontal cortex (mPFC) has revealed dissociable effects on this task, suggesting different roles within working memory for each of these areas. However, further research has shown that mPFC deficits in the rat may only be transient in nature, particularly on the radial maze. The present study was conducted to examine the effects of permanent excitotoxic lesions of the mPFC in the DSWS task across repeated trials to assess whether change in the degree of impairment would occur over time. Results showed that rats with lesions centred on the prelimbic cortex (but with damage extending into the anterior cingulate) were impaired on the post-delay test phase of the DSWS task. This deficit was characterised by increased errors (both across and within phase), earlier error occurrence, and increased latencies. Only the number of choices correct before error improved across repeated test days. These results are consistent with the involvement of the rat mPFC in spatial working memory and response inhibition, supporting previous findings using transient lesions. However, the discovery that rats with mPFC lesions learned to delay the intrusion of errors into their choice sequence extends previous work, and provides support for studies showing that mPFC lesioned rats can improve some aspects of task performance given the opportunity to learn over repeated trials.     

Selective deficits in attentional performance on the 5-choice serial reaction time task following pedunculopontine tegmental nucleus lesions

Sustained attention requires the integrity of basal forebrain cholinergic systems. The pedunculopontine tegmental nucleus (PPTg) has direct and indirect connections (via the thalamus) with the basal forebrain, suggesting that the PPTg may also play an important role in attentional processes. We examined this hypothesis by testing the effects of PPTg lesions in rats on performance in the 5-choice serial reaction time test. Bilateral lesions reduced accuracy, increased errors of omission, and increased the latency to correct responses. The deficits were more severe when neuronal damage was bilateral and concentrated in the posterior PPTg. Attentional demands of the task were increased by decreasing the stimulus duration, the stimulus brightness, or the inter-trial interval, and by introducing random bursts of white noise. These challenges impaired performance of all animals, but the magnitude of deficit was increased in the lesioned group. Conversely, lesion-induced deficits were partially alleviated when the attentional demands of the task were reduced. This pattern of results suggests that PPTg lesions produce a global deficit in attention, rather than a specific impairment in one process. The PPTg may control attentional processes through its direct projections to the forebrain cholinergic system or, indirectly, through activation of thalamocortical projections.     

Unilateral hippocampal damage impairs spatial cognition in rats

Unilateral temporal lobectomy to treat seizure disorders in humans often results in cognitive impairment after the surgery. To determine the potential utility of a rodent model of unilaterally induced cognitive deficits, the present experiment evaluated spatial cognition in adult rats after either left or right hemisphere lesioning of temporal neocortex and underlying hippocampal regions. Evaluation of performance in the eight arm radial maze revealed that both lesioned groups committed more reference memory errors than did nonoperated controls. Working memory errors did not differ statistically between groups. The production of a spatial learning deficit by unilateral damage suggests that this rodent model could serve to test potential improvements in interventional strategies aimed at attenuating cognitive effects of the surgical treatment.     

Excitotoxic lesions of the pedunculopontine tegmental nucleus of the rat. II. Examination of eating and drinking, rotation, and reaching and grasping following unilateral ibotenate or quinolinate lesions

The pedunculopontine tegmental nucleus (PPTg) contains a population of cholinergic neurons thought to be part of the ascending reticular activating system, and non-cholinergic neurons. In the previous study it was shown that various excitotoxins made effective lesions of cholinergic neurons in the PPTg but that quinolinate made smaller lesions in the non-cholinergic population, making it more selective than any other excitotoxin. The purpose of the present experiment was, first, to make lesions of cholinergic neurons throughout the length of the PPTg by infusing toxin at two different sites within it; and second, to examine simple motor activities in rats bearing either quinolinate or ibotenate lesions of the PPTg, and contrast these with the deficits seen after 6-hydroxydopamine (6-OHDA) induced lesions of mesostriatal dopamine (DA)-containing neurons. Post-mortem examination was carried out using choline acetyltransferase (ChAT) and tyrosine hydroxylase (TOH) immunohistochemistry, and routine Nissl staining. Both quinolinate and ibotenate destroyed approximately 75% of ChAT-positive neurons in the PPTg, but damage to non-cholinergic neurons (assessed by Nissl staining) was twice as great following ibotenate as quinolinate. 6-OHDA induced almost complete lesions of mesostriatal DA neurons, assessed by TOH immunohistochemistry. DA depleted rats showed deficits in drinking and spilled more food in the first 2 weeks after surgery, and were unable to reach or grasp food pellets in the staircase test. They also showed strong ipsilateral turning in response to amphetamine and contralateral turning to apomorphine. Quinolinate lesioned rats had no eating or drinking impairment in the home cage but showed a reaching (though not grasping) disability in the staircase test. They had a mild ipsilateral bias following amphetamine. Ibotenate lesioned rats, despite having larger lesions than the quinolinate, showed no deficits in eating or drinking in the home cage, or reaching or grasping disabilities in the staircase test. They did have a mild contralateral bias in response to amphetamine. This dissociation of the effects of quinolinate and ibotenate lesions of the PPTg is consistent with the suggestion that the PPTg has two functionally distinct components, and is attributed to the differential lesion of non-cholinergic neurons by the two excitotoxins.     

Comparison of retention performance between young rats with fimbria-fornix lesions and aged rats in a 14-unit T-maze

Young (3-months) and aged (24-months) male F-344 rats were pretrained in one-way active avoidance in a straight runway for 3 days. Then two 10-trial daily sessions were given in a 14-unit T-maze in which the response requirement was to negotiate each of 5 maze segments within 10 s to avoid footshock. One day or one week after acquisition, bilateral electrolytic lesions were made in the fimbria-fornix of young rats (1-day lesion or 1-week lesion). Corresponding sham operations were made for remaining young rats (1-day sham or 1-week sham). Aged animals did not receive any surgical treatment. One week after surgery, a 10-trial retention test was conducted to assess the lesion effects on retention and to manipulate the interval between acquisition and lesions. Aged animals were tested in the maze 1 week after acquisition. Results revealed that rats with fimbria-fornix lesions exhibited significant impairment compared to sham-operated groups on all retention performance measures including errors, runtime, number of shocks, duration of shock, and alternation errors. The number of errors and alternation errors of lesioned animals were still higher than those of sham-operated animals at the second half of the retention test, whereas other non-cognitive measures for lesioned animals recovered to control levels. The interval between acquisition training and lesions had no influence on retention performance. Although performance of aged rats during acquisition and retention trials was significantly worse than that of young controls and lesioned animals, a similar recovery pattern during retention testing was found for young rats with fimbria-fornix lesions and aged rats, i.e. both groups showed significant declines in non-cognitive measures with less decline in cognitive measures. These results suggest that the fimbria-fornix is partially involved in retention of 14-unit T-maze performance and that the age-related retention deficit observed in this task may be related to impaired transmission through this pathway.     

An examination of the effects of bilateral excitotoxic lesions of the pedunculopontine tegmental nucleus on responding to sucrose reward

The effects of bilateral excitotoxic lesions of the pedunculopontine tegmental nucleus (PPTg) on sucrose intake were examined in three experiments. First, in tests of conditioned place preference using 20% sucrose as the reinforcer, it was shown that lesioned rats, regardless of whether they were food deprived or non-deprived, formed normal place preferences and showed normal amounts of locomotion. However, consumption of 20% sucrose in the pairing trials was increased in the deprived PPTg lesioned rats compared to their matched controls. A second experiment showed that sucrose consumption in the home cage was increased in both deprived and non-deprived PPTg lesioned rats, but only when the concentration of sucrose was greater than 12%: below this there were no differences in intake between the lesioned and control rats. In a third home cage experiment, it was again shown that non-deprived PPTg lesioned rats increased their consumption of 20% sucrose compared to controls. PPTg lesioned rats concomitantly reduced their intake of lab chow such that overall energy intake remained the same as that of control rats. These data are taken to suggest (i) that bilateral excitotoxic lesions of the PPTg increase consumption of sucrose selectively in conditions of high motivational excitement; (ii) that the perception of the rewarding value of 20% sucrose, as judged by place preference, is not affected by these lesions; and (iii) that PPTg lesioned rats are able to adjust their energy intake to accommodate increased sucrose loads. These data are consistent with the hypothesis that bilateral excitotoxic lesions of the PPTg do not affect energy balance regulation or judgment of the hedonic value of sucrose, but that they do affect the control of responding in the face of high levels of motivational excitement.     

Effects of pre-training pedunculopontine tegmental nucleus lesions on delayed matching- and non-matching-to-position in a T-maze in rats

Lesions of the pedunculopontine tegmental nucleus (PPTg) can impair spatial learning tasks, but it is not clear whether those detrimental effects depend on the specific training conditions (for example, number of response choices available) or are secondary to enhanced anxiety. In the present work, rats with either bilateral excitotoxic (ibotenate) lesions of the PPTg (lesion group) or with vehicle infusions (control group) were tested in an elevated plus-maze, in order to measure anxiety-like behaviours and spontaneous locomotion. Subsequently, they were trained in a delayed matching-to-position (DMTP) task in a T-maze (a two-response choice task). After reaching a predefined learning criterion, or after a maximum of 30 training sessions, the animals were trained in a delayed non-matching-to-position (DNMTP) task. Lesioned animals made less grooming episodes, stretch-attend postures and closed arm entries than controls in the elevated plus-maze, suggesting slightly lower anxiety levels. None of the lesioned rats reached the learning criterion for the DMTP, and overall accuracy levels were significantly lower in those rats, compared to controls. In the DNMTP task, lesioned animals showed lower accuracy levels and higher side bias than controls in some of the sessions, but there were no significant differences between the two groups in the proportion of animals reaching the learning criterion. It is concluded that spatial learning deficits induced by damage to the PPTg are not secondary to enhanced anxiety. Instead, those deficits seem to be influenced by several conditions that modify task demands, the number of response choices being only one of such conditions.     

The effects of excitotoxic lesions of the pedunculopontine tegmental nucleus on conditioned place preference to 4%, 12% and 20% sucrose solutions

A number of studies have suggested that the pedunculopontine tegmental nucleus (PPTg) may play a role in reward-related behaviour. The present study was intended to investigate this further using conditioned place preference. In conditioned place preference paradigms the amount of time spent in a preferred environment is proportional to the value of the reinforcement present, until a maximum is reached. In the present experiments we aimed to determine whether this relationship was affected by lesions of the PPTg by examining the formation of a conditioned place preference to either 4%, 12% or 20% sucrose solutions in food-deprived PPTg lesioned rats. The conditioned place preference apparatus had two compartments different in colour, smell and floor texture. During conditioning, rats were restricted to one compartment or the other, one of which was paired with sucrose. This was carried out during 30 min sessions, alternating conditioned or nonconditioned trials for 14 days. On the test day, rats were given access to both compartments through a connecting chamber, and were scored for side preference over 15 min. Both PPTg and sham lesioned rats showed a conditioned place preference to 12% and 20% sucrose, but no place preference was formed by either group to 4% sucrose. There was no significant difference between the groups in the place preference shown. Consumption of 4% sucrose was not affected by excitotoxic lesions of the PPTg, but PPTg lesioned rats consumed significantly more 12% and 20% sucrose than sham controls. This suggests that perception of reward value, as judged by CPP formation, is unchanged by excitotoxic lesions of the PPTg. The increased consumption of 12% and 20% sucrose shown by rats bearing such lesions is therefore not likely to be a product of altered reward perception.     

Habit learning dissociation in rats with lesions to the vermis and the interpositus of the cerebellum

After cerebellar tumors resection, patients show motor skill learning impairments but also cognitive deficits. However, their exact origins remain controversial. Using a rat model of cerebellar injury, we assessed the involvement of two structures often damaged during resection (vermis and interpositus nuclei) on habits development. During extended training of an instrumental task, rats develop response routines that are no longer voluntary or goal-directed but habit-based, evidenced by their insensitivity to changes in the value of the reward. Here we showed that, in contrast to sham or vermis lesioned rats, discrete lesions to interpositus nuclei prevented rats from developing habits with overtraining, without motor difficulties, nor alteration of the instrumental task acquisition. Our results suggest that the role of the cerebellum can be extended from motor skill learning to cognitive routines learning. Similar habit impairment could possibly account for some of the long-term outcome difficulties observed in cerebellar-damaged patients.     

Ventral striatal activation during attribution of stimulus saliency and reward anticipation is correlated in unmedicated first episode schizophrenia patients

Patients with schizophrenia show deficits in motivation, reward anticipation and salience attribution. Several functional magnetic resonance imaging (fMRI) investigations revealed neurobiological correlates of these deficits, raising the hypothesis of a common basis in midbrain dopaminergic signaling. However, investigations of drug-na?ve first-episode patients with comprehensive fMRI tasks are still missing. We recruited unmedicated schizophrenia spectrum patients (N=27) and healthy control subjects (N=27) matched for sex, age and educational levels. An established monetary reward anticipation task in combination with a novel task aiming at implicit salience attribution without the confound of monetary incentive was applied. Patients showed reduced right ventral striatal activation during reward anticipation. Furthermore, patients with a more pronounced hypoactivation attributed more salience to neutral stimuli, had more positive symptoms and better executive functioning. In the patient group, a more differentially active striatum during reward anticipation was correlated positively to differential ventral striatal activation in the implicit salience attribution task. In conclusion, a deficit in ventral striatal activation during reward anticipation can already be seen in drug-na?ve, first episode schizophrenia patients. The data suggest that rather a deficit in differential ventral striatal activation than a generally reduced activation underlies motivational deficits in schizophrenia and that this deficit is related to the aberrant salience attribution.     

Relation between cognitive dysfunction and pseudobulbar palsy in amyotrophic lateral sclerosis.

OBJECTIVES: To examine the relation between cognitive dysfunction and pseudobulbar features in patients with amyotrophic lateral sclerosis (ALS). METHODS: The performance of two patient groups, ALS with pseudobulbar palsy (n = 24) and ALS without pseudobulbar palsy (n = 28), was compared with 28 healthy age matched controls on an extensive neuropsychological battery. Tests used were the national adult reading test, short form of the WAIS-R, recognition memory test, Kendrick object learning test, paired associate learning, Wisconsin card sorting test, verbal fluency, Stroop and negative priming tests, a random movement joystick test, and a computerised Tower of Hanoi test. RESULTS: Tests of executive function showed a pronounced deficit on written verbal fluency in both ALS groups in comparison to controls, which tended to be more prominent in patients with ALS with pseudobulbar palsy. The random movement joystick test (a non-verbal test of intrinsic movement generation) showed an impairment in the generation of random sequences in patients with pseudobulbar palsy only. The computerised Tower of Hanoi showed a subtle planning impairment (shorter planning times) in all the patients with ALS compared with controls on trials requiring more complex solutions. In addition the pseudobulbar patients displayed shorter planning times on complex trials, and tended to solve these trials less accurately. There was also evidence of a deficit for all patients with ALS in comparison with controls on total errors and number of categories achieved on the Wisconsin card sorting test and a strong tendency towards an impairment on a task of selective attention and cognitive inhibition (negative priming). A word recognition memory deficit was showed across both ALS groups. CONCLUSIONS: This study elicited cognitive deficits (involving predominantly executive processes, with some evidence of memory impairment) in patients with ALS and further strengthened the link between ALS and frontal lobe dysfunction, this being more prominent in patients with pseudobulbar palsy. However, cognitive impairments suggestive of extramotor cortical involvement were not exclusive to this subgroup.     

Comparative effects of ibotenic acid- and quisqualic acid-induced lesions of the substantia innominata on attentional function in the rat: further implications for the role of the cholinergic neurons of the nucleus basalis in cognitive processes

Two experiments examined the effects of excitotoxic lesions of the substantia innominata on cholinergic activity in the neocortex and on performance in a paradigm measuring selective attention in the rat. In Expt. 1, ibotenate-induced lesions produced approximately 30% reductions in cortical choline acetyltransferase (ChAT) activity, and damage to wide regions of the substantia innominata and ventral pallidum. The rats were impaired in their ability to localize brief visual targets in a serial reaction time task, as measured by reduced choice accuracy. This impairment was particularly evident at short stimulus durations, but the lesioned rats did not exhibit evidence of primary visual sensory dysfunction and exhibited only minor deficits when the stimuli were presented unpredictably. The deficit was exacerbated when distracting white noise was interpolated into the task. The rats with lesions were also slower to respond correctly, probably resulting partly from the adoption of a speed/error trade-off strategy, and were slower to collect earned food pellets, although they made no more errors of omission than controls. In Expt. 2, quisqualate-induced lesions produced fewer signs of non-specific damage and 50% reductions in cortical ChAT activity. This lesion produced generally qualitatively similar, but weaker effects to those of ibotenate-induced lesions. It was notable that many of the deficits following either ibotenate- or quisqualate-induced lesions lasted for several months after surgery. The results are discussed in terms of the cholinergic hypothesis of cognitive dysfunction. It is argued that lesions of the substantia innominata, including the magnocellular cholinergic neurons of the nucleus basalis of Meynert, produce deficits in attentional processing, which may not result from damage specifically to cholinergic cells. However, the longevity of the effects makes these preparations suitable for further exploration of the restorative effects of cholinergic treatments.     

The Basis of Visual Constructional Disability in Patients with Unilateral Cerebral Lesions

Patients with left and right unilateral hemispheric lesions were compared on the Form Assembly Task, a visual construction task requiring perceptual but not executive, motor, or verbal skills. Right lesioned patients were inferior to lefts and normals in both degree and frequency of impairment. Performances on the assembly task and two visual discrimination tasks were correlated among right but not left lesioned patients. Left lesioned patients took significantly longer to achieve maximum level of performance than either rights or normals. Neither sex nor duration of lesion affected Form Assembly performance. Results were consistent with the hypothesis that visual perceptual deficits underlie constructional difficulties among right but not left lesioned patients.     

Deficient reinforcement learning in medial frontal cortex as a model of dopamine-related motivational deficits in ADHD

Attention Deficit/Hyperactivity Disorder (ADHD) is a pathophysiologically complex and heterogeneous condition with both cognitive and motivational components. We propose a novel computational hypothesis of motivational deficits in ADHD, drawing together recent evidence on the role of anterior cingulate cortex (ACC) and associated mesolimbic dopamine circuits in both reinforcement learning and ADHD. Based on findings of dopamine dysregulation and ACC involvement in ADHD we simulated a lesion in a previously validated computational model of ACC (Reward Value and Prediction Model, RVPM). We explored the effects of the lesion on the processing of reinforcement signals. We tested specific behavioral predictions about the profile of reinforcement-related deficits in ADHD in three experimental contexts; probability tracking task, partial and continuous reward schedules, and immediate versus delayed rewards. In addition, predictions were made at the neurophysiological level. Behavioral and neurophysiological predictions from the RVPM-based lesion-model of motivational dysfunction in ADHD were confirmed by data from previously published studies. RVPM represents a promising model of ADHD reinforcement learning suggesting that ACC dysregulation might play a role in the pathogenesis of motivational deficits in ADHD. However, more behavioral and neurophysiological studies are required to test core predictions of the model. In addition, the interaction with different brain networks underpinning other aspects of ADHD neuropathology (i.e., executive function) needs to be better understood.     

Different function of pedunculopontine GABA and glutamate receptors in nucleus accumbens dopamine, pedunculopontine glutamate and operant discriminative behavior

The nucleus accumbens, as the main input structure of the ventral basal ganglia loop, is described as a limbic-motor interface. Dopamine input to nucleus accumbens modulates processing of concurrent glutamate input from limbic structures carrying motor and motivational information. There is evidence that these dopamine/glutamate interactions are fundamentally involved in response selection processes. However, the pedunculopontine tegmental nucleus (PPTg) in the brainstem is connected with limbic structures as well as dopaminergic midbrain areas, which also project to the nucleus accumbens. Furthermore, behavioral studies implicate the PPTg in complex, motivated behavior. Thus, the PPTg might be involved in motivated behavior by influencing response selection processes in the nucleus accumbens. In this study we used in vivo microdialysis in freely moving rats in order to inhibit (100, 200, 300 and 400 microm baclofen) or stimulate [5, 12.5, 25 or 50 micromalpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA)] the PPTg in animals that are performing an operant discrimination task for food reward. The behavioral consequences were correlated with dopamine and glutamate levels in nucleus accumbens and PPTg, respectively. PPTg inhibition by local GABAB receptors impaired the response rate and accuracy of performance in the operant discrimination task. PPTg stimulation by local AMPA receptors exclusively impaired the response rate. Both treatments blocked the performance-driven dopamine signal in nucleus accumbens, whereas glutamate in PPTg was enhanced after AMPA administration only. The data indicate that the PPTg functionally participates in a network of subcortical and cortical structures, which is responsible for the execution of motivated behavior and response selection processes.     

Evidence that response inhibition is a primary deficit in ADHD

The present study examined response inhibition in children with attention deficit hyperactivity disorder (ADHD; n = 58) and controls (n = 84) using three go/no-go tests -- one with high working memory demand (cognitive), one with low working memory demand (simple), and one with rewards and response costs (motivation linked) in which emphasis was on reward for responding to "go" stimuli. Results of a repeated measure analysis of variance showed a significant effect of diagnosis for errors of commission for the simple, cognitive, and motivation-linked go/no-go tests, such that children with ADHD made significantly more errors than controls. Furthermore, a significant effect of test was noted across groups, such that both children in the ADHD and control groups performed worse on the cognitive and motivation-linked tests than they did on the simple test. The diagnosis by test interaction was not significant, suggesting that ADHD participants showed a similar degree of impairment to that of controls, regardless of the degree of working memory load or feedback provided in the test. In children with ADHD, response inhibition appears to be a primary deficit that is observed even when executive function demands of tasks are minimal. Although increasing working memory demand appears to impede response inhibition, this effect is similar in ADHD and typically developing children.     

Aversive stimulus attenuates impairment of acquisition in a delayed match to position T-maze task caused by a selective lesion of septo-hippocampal cholinergic projections

Infusion of 192 IgG-saporin (SAP) into the medial septum (MS) of rats selectively destroys cholinergic neurons projecting to the hippocampus and impairs acquisition of a delayed matching to position (DMP) T-maze task. The present study evaluated whether introduction of a mild aversive stimulus 30 min prior to training would attenuate the deficit in DMP acquisition caused by the SAP lesions. Male Sprague-Dawley rats received medial septal infusions of either artificial cerebrospinal fluid or SAP (0.22 microg in 1.0 microl). Fourteen days later, all animals were trained to perform the DMP task. Half of the SAP-treated animals and controls received an intraperitoneal injection of saline each day, 30 min prior to training. Results show that intraperitoneal saline attenuated the impairment in DMP acquisition in SAP lesioned rats. These results suggest that a mild aversive stimulus can attenuate cognitive deficits caused by medial septal cholinergic lesions.     

A study of hippocampal structure-function relations along the septo-temporal axis

This study examined structural-functional differences along the septo-temporal axis of hippocampus using radial-maze tasks that involved two different memory processes [reference memory (RM) and working memory (WM)], and the use of two kinds of information (spatial vs. nonspatial cue learning). In addition, retention of the nonspatial cue task was tested nine weeks following completion of acquisition, and the rats then underwent discrimination reversal training. Ibotenic acid lesions limited to either the dorsal pole, intermediate area, or ventral pole had minimal effects on acquisition of the complex place and cue discrimination tasks. The one exception was that rats with lesions confined to the dorsal third of hippocampus made more WM errors on the spatial task (but not the cue task) early in training. Selective lesions of the three hippocampal regions had no effects on either long-term retention or reversal of the nonspatial cue discrimination task. In contrast, rats that had all of the hippocampus removed were severely impaired in learning the spatial task, making many RM and WM errors, whereas on the nonspatial cue task, the impairment was limited to WM errors. Further analysis of the WM errors made in acquisition showed that rats with complete lesions were significantly more likely on both the spatial and nonspatial cue tasks to reenter arms that had been baited and visited on that trial compared to arms that had not been baited. A similar pattern of errors emerged for complete hippocampal lesioned rats during reversal discrimination. This pattern of errors suggests that in addition to an impairment in handling spatial information, complete removal of hippocampus also interferes with the ability to inhibit responding to cues that signal reward under some conditions but not under others. The finding that selective lesions limited to the intermediate zone of the hippocampus produce no impairment in either WM ("rapid place learning") or RM in our radial maze tasks serve to limit the generality of the conclusion of Bast et al. (Bast et al. (2009) PLos Biol 7:730-746) that the intermediate area is needed for behavioral performance based on rapid learning about spatial cues.     

Loss of hippocampal CA1 neurons and learning impairment in subicular lesioned rats

30-Day-old male Wistar rats were tested for acquisition and retention of operant conditioned behavior after bilateral subicular lesions made either electrolytically or chemically (ibotenic acid). The acquisition of operant learning was carried out in lesioned rats by assessing the number of sessions required to learn the operant task, whereas the retention test was performed after lesions by assessing performance on a previously learnt operant task. The acquisition of pedal press operant learning was significantly delayed in both types of lesioned rats, without any impairment in the retention of the previously learned task after lesioning. In these animals the cell densities were quantified in cresyl violet-stained sections in different subfields of hippocampus. Following the lesion of subiculum, selective degeneration of CA1 cells without the involvement of other hippocampal subfields was observed. This might be due to the loss of target area (subiculum) through which hippocampus is connected with neocortical and subcortical structures. This, in turn, might have resulted in behavioral deficits. The data suggest that the subiculum might be involved in the acquisition of new information rather than in retention.     

Disruption of self-organized actions in monkeys with progressive MPTP-induced parkinsonism: II. Effects of reward preference

The motor and cognitive symptoms of Parkinson's disease (PD) are well documented, but little is known about the functionality of motivational processes mediated by the limbic circuits of basal ganglia. The aim of this study was to test the ability of motivational processes to direct and to urge behaviour, in four vervet monkeys (Cercopithecus aethiops) progressively intoxicated with systemic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) injections (0.3-0.4 mg/kg every 4-7 days). In the food preference task, the monkeys had to retrieve two types of directly visible food, simultaneously available in the wells of a reward board. At all stages of MPTP-induced parkinsonism, the monkeys continued to take their favourite food first. In the symbol discrimination task, the wells were covered with sliding plaques cued by symbols indicating the absence or presence of a reward, and the different types of food were blocked in separate sessions. Monkeys with mild or moderate parkinsonism made fewer attempts and took longer to retrieve non-preferred compared with preferred rewards. These results indicate that motivational processes are still able to direct (food preference task) and to urge (symbol discrimination task) behaviour in MPTP-lesioned monkeys. Such a functional preservation may be related to the relatively spared dopaminergic innervation of the limbic circuits that we found in our monkeys, in agreement with the literature on humans. Furthermore, the frequency of executive disorders (such as hesitations and freezing) appeared to be much lower with the preferred rewards. Thus, the preserved motivational processes may help to overcome executive dysfunction in the early stages of human PD.