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PubMedDate not supplied

Enhanced DRL and impaired forced-choice alternation performance following hippocampal lesions in the pigeon.

In four experiments, pigeons with bilateral lesions of the hippocampus were compared to unoperated control birds and operated control subjects that received bilateral lesions of the neostriatum on tasks sensitive to hippocampal damage in mammals. Consistent with the mammalian literature, hippocampal birds were impaired on forced-choice alternation in the T-maze, although they were unimpaired on spatial alternation and reversal learning in an operant chamber. Furthermore, in contrast to hippocampal mammals, hippocampal pigeons showed enhanced performance on a differential reinforcement of low-rates of responding schedule of reinforcement. The results are discussed with respect to a behavioural homology between the avian and mammalian hippocampal formations.

Animals↗
PubMed2005

Neurologic examination abnormalities in children with bipolar disorder or attention-deficit/hyperactivity disorder.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BPD) are frequently comorbid and overlapping diagnoses. To move beyond diagnosis toward unique pathophysiology, we evaluated both ADHD and BPD children for neurologic examination abnormalities (NEAs) in comparison with normal control (NC) children. METHODS: We performed the Revised Physical and Neurological Examination for Soft Signs in three groups (ADHD, BPD, NC). Then, a rater blind to diagnosis evaluated their motor performance. Results were analyzed with a multiple analysis of covariance. RESULTS: Subjects with ADHD were impaired on repetitive task reaction time. In contrast, pediatric BPD subjects, both with and without comorbid ADHD, were impaired on sequential task reaction time. CONCLUSIONS: This differential pattern of NEAs by diagnosis suggests pathophysiologic differences between ADHD and BPD in children. Repetitive motor performance requires inhibition of nonrelevant movements; ADHD subjects' impairment in this domain supports the hypothesis that ADHD involves a core deficit of fronto-striato-basal ganglia neurocircuitry. In contrast, BPD subjects' impaired sequential motor performance is consistent with behavioral data showing impaired attentional set-shifting and reversal learning in BPD subjects. Further study, going beyond symptom description to determine pathophysiologic differences, is required to refine neuronal models of these often comorbid diagnoses.

Adolescent↗
PubMed1993

Effects of fetal hippocampal field grafts on ischaemic-induced deficits in spatial navigation in the water maze.

Transitory global cerebral ischaemia induced in rats by four vessel occlusion for 15 min produced substantial loss of CA1 cells in dorsal hippocampus, and minimal damage in other intra- and extrahippocampal forebrain regions examined. Ischaemic rats showed long-lasting deficits in spatial navigation in the water-maze, consisting of impaired learning to locate a hidden platform in a novel pool, a substantial increase in time spent searching close to the platform without finding it, and moderate deficits in matching to position in a working memory task. Groups of ischaemic rats were implanted with fetal tissue dissected from hippocampal CA1 field, containing glutamatergic CA1 pyramidal cells, from dentate gyrus, containing glutamatergic dentate granule cells, and from basal forebrain, containing cholinergic cells, with grafts sited in the alveus above the damaged CA1 region, for comparison with non-grafted ischaemic and non-ischaemic control groups, over a series of tests from four to 20 weeks after grafting. All ischaemic groups showed comparable acquisition deficits prior to transplantation, and similar loss of CA1 cells on post mortem examination. When tested in a familiar pool in retention and reversal learning of the original platform position, and a working memory task, all ischaemic rats performed better than in initial acquisition. However, rats receiving CA1 grafts showed the most consistent improvement relative to ischaemic controls. When tested in a second (i.e. novel) pool, ischaemic rats again showed marked impairment, whereas rats with CA1 grafts were significantly superior, and learned as rapidly as non-ischaemic controls. The performance of groups with dentate granule and basal forebrain grafts was similar to that of the non-grafted ischaemic control group throughout testing. These results suggest that ischaemic rats are impaired in the adaptive use of spatial information, as shown by acquisition and working memory deficits, but not in long- or short-term memory storage processes, and are also impaired in precise spatial localization. The effects of CA1 grafts in restoring spatial abilities, shown most clearly when rats were tested in a novel environment, suggest that these grafts may have assisted with repair to the damaged host circuit, rather than acted through the release of an appropriate neurotransmitter, since the glutamatergic dentate granule grafts were ineffective. However, CA1 grafts showed better survival and growth than the other types of transplant, so that functional recovery may have been related to graft viability rather than to the specific type of graft.

Animals↗
PubMedDate not supplied

REM sleep and neural nets.

The broad features of rapid eye movement (REM) sleep are reviewed. Memory storage in the brain is probably quite unlike that in a digital computer, being distributed, superimposed and robust. Such memory systems are easily overloaded. If the stored memories share common features, random stimulation often produces mixed outputs. Simulations show that such overloading can be reduced by a process we call 'reverse learning'. We propose that this process is what is happening in REM sleep and that it explains in an unforced manner the condensation commonly found in dreams. Evidence for and against the proposed theory is discussed and several alternative theories are briefly described. The absence of REM sleep in the Enchidna and in two species of dolphins (that have relatively large brains) suggests that REM may allow the brain to be smaller than if REM were lacking.

Animals↗
PubMedDate not supplied

[Dependence of the reversal training of rats in a Y-maze and their haloperidol sensitivity on the estrous cycle phase].

In female rats estrous cycle related variations were found in reversal learning in a Y-maze. Low intersession fluctuations of errors and a high number of well relearning rats were obtained on the day of diestrus I as compared with estrus. The improvement of avoidance behaviour by haloperidol (0.1 mg/kg) also was better in diestrus I. The estrous cycle dependent variations of the behavior and neuroleptic effect may be a result of periodicity of ovarial hormones secretion and their influences on the brain dopaminergic systems.

Animals↗
PubMed2004

Mice lacking dopamine D2 and D3 receptors exhibit differential activation of prefrontal cortical neurons during tasks requiring attention.

Mice lacking dopamine D2 and D3 receptors and wildtype littermates were tested in a two-choice perceptual discrimination test that is dependent upon optimal functioning of the prefrontal cortex. Both mutants showed no deficits in attending to the perceptual stimuli or in shifting attention between stimulus dimensions. However, the performance of both mutants differed from the wildtype in different test phases. D2 mutants exhibited significant impairment in the first compound discrimination, indicating deficits in the initial acquisition of the task-governing rules. In contrast, D3 mutants performed significantly better in a set-shifting phase that required reversal learning. The higher response accuracy of D3 mutants was also accompanied by significantly increased response latency. A stereological assessment of test-induced expression of the c-fos gene in neurons of the anterior cingulate and prelimbic/infralimbic cortices revealed highest activation in D3 mutants, intermediate activation in wildtype and lowest activation in D2 mutants, indicating that response accuracy in the cognitive test correlates with the magnitude of prefrontal cortical activation regardless of which test phases revealed different performances. The study illustrates that dopamine differentially modulates prefrontal cortical activity during tasks requiring attention depending upon the type of D2-like receptor that is activated.

Animals↗
PubMed2000

Impaired social response reversal. A case of 'acquired sociopathy'.

In this study, we report a patient (J.S.) who, following trauma to the right frontal region, including the orbitofrontal cortex, presented with 'acquired sociopathy'. His behaviour was notably aberrant and marked by high levels of aggression and a callous disregard for others. A series of experimental investigations were conducted to address the cognitive dysfunction that might underpin his profoundly aberrant behaviour. His performance was contrasted with that of a second patient (C.L.A.), who also presented with a grave dysexecutive syndrome but no socially aberrant behaviour, and five inmates of Wormwood Scrubs prison with developmental psychopathy. While J.S. showed no reversal learning impairment, he presented with severe difficulty in emotional expression recognition, autonomic responding and social cognition. Unlike the comparison populations, J.S. showed impairment in: the recognition of, and autonomic responding to, angry and disgusted expressions; attributing the emotions of fear, anger and embarrassment to story protagonists; and the identification of violations of social behaviour. The findings are discussed with reference to models regarding the role of the orbitofrontal cortex in the control of aggression. It is suggested that J.S.'s impairment is due to a reduced ability to generate expectations of others' negative emotional reactions, in particular anger. In healthy individuals, these representations act to suppress behaviour that is inappropriate in specific social contexts. Moreover, it is proposed that the orbitofrontal cortex may be implicated specifically either in the generation of these expectations or the use of these expectations to suppress inappropriate behaviour.

Antisocial Personality Disorder↗
PubMed2002

A proposed function for hippocampal theta rhythm: separate phases of encoding and retrieval enhance reversal of prior learning.

The theta rhythm appears in the rat hippocampal electroencephalogram during exploration and shows phase locking to stimulus acquisition. Lesions that block theta rhythm impair performance in tasks requiring reversal of prior learning, including reversal in a T-maze, where associations between one arm location and food reward need to be extinguished in favor of associations between the opposite arm location and food reward. Here, a hippocampal model shows how theta rhythm could be important for reversal in this task by providing separate functional phases during each 100-300 msec cycle, consistent with physiological data. In the model, effective encoding of new associations occurs in the phase when synaptic input from entorhinal cortex is strong and long-term potentiation (LTP) of excitatory connections arising from hippocampal region CA3 is strong, but synaptic currents arising from region CA3 input are weak (to prevent interference from prior learned associations). Retrieval of old associations occurs in the phase when entorhinal input is weak and synaptic input from region CA3 is strong, but when depotentiation occurs at synapses from CA3 (to allow extinction of prior learned associations that do not match current input). These phasic changes require that LTP at synapses arising from region CA3 should be strongest at the phase when synaptic transmission at these synapses is weakest. Consistent with these requirements, our recent data show that synaptic transmission in stratum radiatum is weakest at the positive peak of local theta, which is when previous data show that induction of LTP is strongest in this layer.

Algorithms↗
PubMed1986

Simultaneous brightness discrimination and reversal: the effects of amphetamine administration in the two stages.

Rats were trained in a Y-maze on a two-choice simultaneous brightness discrimination with light as S+ and dark as S- (Stage 1), and were then switched to reversal, where the reinforcement contingencies of the original training were reversed (Stage 2). d-Amphetamine, 1 mg/kg, was administered in a 2 X 2 design, i.e., drug-no drug in Stage 1 and drug-no drug in Stage 2. The administration of the drug in Stage 1 improved the acquisition of the initial brightness discrimination and facilitated reversal learning independently of the drug administered in Stage 2. In addition, the administration of the drug in Stage 2 only improved performance towards the end of reversal training. The results indicate that amphetamine enhances the attention to, or the associability of, the discriminative stimuli, leading to a rapid learning to these stimuli under changed contingencies of reinforcement.

Animals↗
PubMed1993

Medial frontal cortex lesions: deficits and treatment with nimodipine.

Rats with bilateral lesions of the medial frontal cortex were tested in a T-maze for the ability to learn a position habit and to make four reversals of it. Rats with medial frontal cortical lesions showed deficits in reversal learning. In addition, they were found to be hyperactive in an open field. Treatment with the dihydropyridine calcium channel antagonist, nimodipine, did not reduce these behavioral deficits.

Analysis of Variance↗
PubMed1991

Effect of amino acid supplementation to a low-protein diet on brain neurotransmitters and memory-learning ability of rats.

The supplementation of methionine and threonine to a 10% soy protein isolate diet caused sharp decreases in the concentrations of brain tryptophan, serotonin and 5HIAA (5-hydroxyindole acetic acid) (e.g., in the hypothalamus, hippocampus, amygdala, locus coeruleus and brain stem). The serum tryptophan ratio (i.e., the ratio of the serum concentration of tryptophan to the sum of the concentrations of other large neutral amino acids, such as tyrosine, phenylalanine, leucine, isoleucine, valine and methionine) significantly decreased. The changes in catecholamines were small on the supplementation of amino acids to the soy protein diet. In the brightness-discrimination learning test, the number of total responses (R+, correct; R-, incorrect) of rats fed the amino acid-supplemented diet increased as compared with that of rats fed the nonsupplemented diet. The correct response ratio in the primary learning test did not change, but in the reverse learning test, the response ratio of rats fed the amino acid-supplemented diet increased. Therefore, it may be considered that the learning ability is correlated with the nutritional state.

Amino Acids↗
PubMed2005

Hallmarks of a common forebrain vertebrate plan: specialized pallial areas for spatial, temporal and emotional memory in actinopterygian fish.

In mammals and birds different pallial forebrain areas participate in separate memory systems. In particular, the hippocampal pallium is implicated in spatial memory and temporal attribute processing, whereas the amygdalar pallium is involved in emotional memory. Here we analyze the involvement of teleost fish lateral and medial pallia, proposed as homologous to the hippocampus and amygdala, respectively, in a variety of learning and memory tasks, such as spatial memory; reversal learning; delay or trace motor classical conditioning; heart rate, emotional classical conditioning; and two way active avoidance conditioning. Results show that the damage to the lateral pallium produces a profound deficit in spatial learning and memory in teleost fish. In addition, lateral pallium lesions produce a significant deficit in trace classical conditioning, whereas they have no significant effects on delay conditioning, or in heart rate conditioning. In contrast, medial pallium lesions disrupt emotional, heart rate conditioning and avoidance conditioning, but spare spatial memory and temporal stimulus processing. These data demonstrate a striking functional similarity between the medial and lateral pallia of teleost fish and the pallial amygdala and hippocampal pallium of land vertebrates, respectively. The reviewed evidence suggest that these two separate memory systems, the hippocampus-dependent spatial, relational or temporal memory system, and the amygdala based emotional memory system, could have appeared early during evolution, having conserved their functional identity through vertebrate phylogenesis.

Animals↗
PubMed2005

Neurocognitive and psychotiform behavioral alterations and enhanced hippocampal long-term potentiation in transgenic mice displaying neuropathological features of human alpha-mannosidosis.

Mice with alpha-mannosidase gene inactivation provide an experimental model for alpha-mannosidosis, a lysosomal storage disease with severe neuropsychological and psychopathological complications. Neurohistological alterations in these mice were similar to those in patients and included vacuolations and axonal spheroids in the CNS and peripheral nervous system. Vacuolation was most prominent and evenly distributed in neuronal perikarya of the hippocampal CA2 and CA3 regions, whereas CA1 and dentate gyrus were weakly or not affected. Field potential recordings from CA1 region in hippocampal slices showed enhanced theta burst-induced long-term potentiation (LTP) in alpha-mannosidase-deficient mice. Longitudinal assessment in age-matched alpha-mannosidase-deficient and wild-type littermates, using an extended test battery, demonstrated a neurocognitive and psychotiform profile that may relate to the psychopathological alterations in clinical alpha-mannosidosis. Brainstem auditory-evoked potentials and basic neuromotor abilities were not impaired and did not deteriorate with age. Exploratory and conflict tests revealed consistent decreases in exploratory activity and emotional blunting in the knock-out group. alpha-Mannosidosis mice were also impaired in aversively motivated learning and acquisition of signal-shock associations. Acquisition and reversal learning in the water maze task, passive avoidance learning in the step-through procedure, as well as emotional response conditioning in an operant procedure were all impaired. Acquisition or shaping of an appetitive instrumental conditioning task was unchanged. Appetitive odor discrimination learning was only marginally impaired during shaping, whereas both the discrimination and reversal subtasks were normal. We propose that prominent storage and enhanced LTP in hippocampus have contributed to these specific behavioral alterations in alpha-mannosidase-deficient mice.

Animals↗
PubMed1982

Eye movements of monkeys during discrimination learning: role of visual scanning.

Four experiments were conducted on stumptailed monkeys (Macaca arctoides) to determine whether the high levels of visual scanning (shifts in fixation from one discriminative stimulus to the other) seen during discrimination learning play a necessary role in this learning. In Experiments 1 and 2, the monkeys were given a series of two-choice, dot-pattern discrimination reversal problems. Normal visual scanning before a choice response was allowed during all but the reversal trials of half of the problems. On these latter trials, the discriminative stimuli were replaced by an uninformative stimulus after the animals made more than one visual fixation on each discriminative stimulus. Thus, on these trials, the animals were limited, in terms of the information received, to the empirically determined minimum number of scans necessary to maintain high levels of performance on such problems. In both experiments, which differed primarily in the number and type of uninformative stimuli used, the rate of reversal learning was markedly retarded by the experimental condition, with the effect persisting over a long series of problems. The magnitude of the effect was unrelated to the similarity of the uninformative stimulus to the discriminative stimuli. In Experiment 3, the monkeys were given a series of discrimination problems without reversals, during half of which the experimental condition was in effect. The results were similar to those of the first two experiments. Experiment 4 was similar to the preceding experiment except that, under the experimental condition, each trial began with the uninformative stimuli, which were replaced by the discriminative stimuli when visual scanning occurred. The uninformative stimuli had no clear-cut effect on discrimination learning in this experiment. These experiments indicate that the information provided by above-minimum levels of scanning is not necessary for discrimination learning per se, but it dose appear necessary for efficient discrimination learning.

Animals↗
PubMed1998

Effect of reduced myristoylated alanine-rich C kinase substrate expression on hippocampal mossy fiber development and spatial learning in mutant mice: transgenic rescue and interactions with gene background.

The myristoylated alanine-rich C kinase substrate (MARCKS) is a prominent protein kinase C (PKC) substrate in brain that is expressed highly in hippocampal granule cells and their axons, the mossy fibers. Here, we examined hippocampal infrapyramidal mossy fiber (IP-MF) limb length and spatial learning in heterozygous Macs mutant mice that exhibit an approximately 50% reduction in MARCKS expression relative to wild-type controls. On a 129B6(N3) background, the Macs mutation produced IP-MF hyperplasia, a significant increase in hippocampal PKCepsilon expression, and proficient spatial learning relative to wild-type controls. However, wild-type 129B6(N3) mice exhibited phenotypic characteristics resembling inbred 129Sv mice, including IP-MF hypoplasia relative to inbred C57BL/6J mice and impaired spatial-reversal learning, suggesting a significant contribution of 129Sv background genes to wild-type and possibly mutant phenotypes. Indeed, when these mice were backcrossed with inbred C57BL/6J mice for nine generations to reduce 129Sv background genes, the Macs mutation did not effect IP-MF length or hippocampal PKCepsilon expression and impaired spatial learning relative to wild-type controls, which now showed proficient spatial learning. Moreover, in a different strain (B6SJL(N1), the Macs mutation also produced a significant impairment in spatial learning that was reversed by transgenic expression of MARCKS. Collectively, these data indicate that the heterozygous Macs mutation modifies the expression of linked 129Sv gene(s), affecting hippocampal mossy fiber development and spatial learning performance, and that MARCKS plays a significant role in spatial learning processes.

Animals↗
PubMed2003

Rapid reversal of stress induced loss of synapses in CA3 of rat hippocampus following water maze training.

The impact was examined of exposing rats to two life experiences of a very different nature (stress and learning) on synaptic structures in hippocampal area CA3. Rats were subjected to either (i) chronic restraint stress for 21 days, and/or (ii) spatial training in a Morris water maze. At the behavioural level, restraint stress induced an impairment of acquisition of the spatial response. Moreover, restraint stress and water maze training had contrasting impacts on CA3 synaptic morphometry. Chronic stress induced a loss of simple asymmetric synapses [those with an unperforated postsynaptic density (PSD)], whilst water maze learning reversed this effect, promoting a rapid recovery of stress-induced synaptic loss within 2-3 days following stress. In addition, in unstressed animals a correlation was found between learning efficiency and the density of synapses with an unperforated PSD: the better the performance in the water maze, the lower the synaptic density. Water maze training increased the number of perforated synapses (those with a segmented PSD) in CA3, both in stressed and, more notably, in unstressed rats. The distinct effects of stress and learning on CA3 synapses reported here provide a neuroanatomical basis for the reported divergent effects of these experiences on hippocampal synaptic activity, i.e. stress as a suppressor and learning as a promoter of synaptic plasticity.

Animals↗
PubMed1999

Discrimination, reversal, and shift learning in Huntington's disease: mechanisms of impaired response selection.

In a series of three experiments, we investigated different aspects of response selection in early-stage clinically symptomatic Huntington's disease (HD) patients in the context of discrimination learning. A series of structurally related response selection tasks involving discrimination, reversal, and shift learning were employed. In Experiment 1, the mechanisms of our previously reported [37] finding of impaired extra-dimensional shift learning were explored. The results suggested that impaired shift learning in HD is a result of perseverative responding. In Experiment 2, performance on a concurrent-pair (CP) discrimination and reversal task was examined. HD patients showed no deficits in CP discrimination learning or reversal. In Experiment 3, the performance of HD patients on a probabilistic discrimination and reversal task was examined. HD patients were impaired in the learning of a probabilistic discrimination, and also its reversal. This reversal deficit was again the result of perseverative responding. In addition, there was a strong correlation between HD patients' activities of daily living scores and reversal errors. The result are consistent with current theories of the role of the basal ganglia in cognition, and suggest specific impairments in response selection mechanisms in HD, in particular, in overcoming selection biases based on prior reinforcement.

Adult↗
PubMed2001

Impaired inhibition of conditioned responses produced by subchronic administration of phencyclidine to rats.

Several recent investigations have suggested that an important function of the frontostriatal system is inhibitory response control, and we previously reported that subchronic exposure to phencyclidine (PCP) produced deficits in inhibitory control in monkeys. The current studies were designed to examine whether subchronic administration of PCP to rats would subsequently affect the ability to inhibit conditioned responses when relationships between reward and stimuli of affective significance change. First, the effects of long-term exposure to PCP on acquisition of a novel, concurrent discrimination or reversal learning were assessed; PCP-treated rats were selectively impaired in the ability to acquire the reversal of an already-learned stimulus-reward association. Furthermore, there were no effects of PCP treatment on the learning of a novel instrumental response; however, PCP-treated rats produced more responses during extinction of instrumental responding than did control subjects. Finally, PCP-treated rats produced more responses for a conditioned reinforcer than did control rats. These data suggest that PCP-treated rats are impaired in their ability to modulate behavior based upon new or changing information about stimulus-reward associations, possibly due to an inability to inhibit conditioned responding towards incentive stimuli. These effects may have relevance to mental disorders involving affective impairments and impulsivity, including schizophrenia, obsessive-compulsive disorders, and drug abuse.

Animals↗