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At least 613 records · Page 34Linked to original sources
PubMed1988

Neocortical transplants in the micrencephalic rat brain: morphology and behavior.

Normal fetal (E18) neocortical tissue transplanted into the hypoplastic posterior neocortex of infant (10 +/- 2-day-old) rats with transplacentally induced micrencephaly developed into very large, healthy, and permanent transplants. Although the cellular organization within the transplants rarely resembled that of normal rat neocortex, the transplants formed a broad area of interface with the host brain and established fiber connections with it. When tested at 2 months and 1-year-of-age, the presence of the transplant had no significant effect on the typically abnormal performance of micrencephalic rats on two tests of unspecific function, open field activity and maze learning. However, a small group of micrencephalic rats in whom the transplant tissue had failed to fill in the small brain lesions inescapably inflicted during surgery, showed greater behavioral deficits than the micrencephalic controls, suggesting that the transplant had corrected the lesion effect.

Animals↗
PubMed1993

Behavioural effects of piperonyl butoxide in male mice.

Piperonyl butoxide was administered to male mice from 5 to 12 weeks of age in the diet at levels of 0 (control), 0.15, 0.30, and 0.60%, and some behavioural parameters were measured. The animals performed three trials in multiple water T-maze at 10 weeks of age, and the number of errors was significantly decreased in treatment groups on the 3rd trial, while there was no biologically significant effect of piperonyl butoxide on maze learning. The motor activity of the exploratory behaviour was measured by ANIMATE AT-420 at 8 and 11 weeks of age. At 8 weeks of age, some parameters were increased in the 0.30% group, while there was no consistent compound- or dose-related effect. At 11 weeks of age, some parameters were different in treatment groups, and there were biologically consistent significant effects; i.e., number of movements, movement time, total distance, average speed, and number of turnings increased. From these results, piperonyl butoxide showed adverse effects on the motor activity of the exploratory behaviour in male mice.

Animals↗
PubMedDate not supplied

Behavioral and neuroanatomical sequelae of prenatal naloxone administration in the rat.

Pregnant Long-Evans hooded rats were dosed subcutaneously with 1 or 5 mg/kg/day naloxone hydrochloride, or an equal volume of vehicle, from gestational Day 4 (GD4) through GD19. Offspring were assessed for development of righting reflex, negative geotaxis, and open field activity, and for acquisition of a Warden maze; offspring sacrificed at postnatal Day (PND) 21 were assessed for several parameters of cerebellar, hippocampal, and motor cortical morphology. Five mg/kg/day naloxone accelerated development of negative geotaxis and righting reflex, while 1 mg/kg/day naloxone tended to slow development. Low dose females had significantly more errors than controls on the first day of maze learning. The high dose group had a significantly higher concentration of granule cells in the curvature of the dentate gyrus than controls; other neuroanatomical measures were unaffected by dosing. These findings confirm and extend previous work indicating that prenatal exposure to naloxone may alter neurobehavioral development in the rat.

Animals↗
PubMed2006

Pomegranate juice decreases amyloid load and improves behavior in a mouse model of Alzheimer's disease.

Although there are no proven ways to delay onset or slow progression of Alzheimer's disease (AD), studies suggest that diet can affect risk. Pomegranates contain very high levels of antioxidant polyphenolic substances as compared to other fruits and vegetables. Polyphenols have been shown to be neuroprotective in different model systems. We asked whether dietary supplementation with pomegranate juice (PJ) would influence behavior and AD-like pathology in a transgenic mouse model. Transgenic mice (APP(sw)/Tg2576) received either PJ or sugar water control from 6 to 12.5 months of age. PJ-treated mice learned water maze tasks more quickly and swam faster than controls. Mice treated with PJ had significantly less (approximately 50%) accumulation of soluble Abeta42 and amyloid deposition in the hippocampus as compared to control mice. These results suggest that further studies to validate and determine the mechanism of these effects, as well as whether substances in PJ may be useful in AD, should be considered.

Alzheimer Disease↗
PubMed2004

Reliability of internal prediction/estimation and its application. I. Adaptive action selection reflecting reliability of value function.

This article proposes an adaptive action-selection method for a model-free reinforcement learning system, based on the concept of the 'reliability of internal prediction/estimation'. This concept is realized using an internal variable, called the Reliability Index (RI), which estimates the accuracy of the internal estimator. We define this index for a value function of a temporal difference learning system and substitute it for the temperature parameter of the Boltzmann action-selection rule. Accordingly, the weight of exploratory actions adaptively changes depending on the uncertainty of the prediction. We use this idea for tabular and weighted-sum type value functions. Moreover, we use the RI to adjust the learning coefficient in addition to the temperature parameter, meaning that the reliability becomes a general basis for meta-learning. Numerical experiments were performed to examine the behavior of the proposed method. The RI-based Q-learning system demonstrated its features when the adaptive learning coefficient and large RI-discount rate (which indicate how the RI values of future states are reflected in the RI value of the current state) were introduced. Statistical tests confirmed that the algorithm spent more time exploring in the initial phase of learning, but accelerated learning from the midpoint of learning. It is also shown that the proposed method does not work well with the actor-critic models. The limitations of the proposed method and its relationship to relevant research are discussed.

Acclimatization↗
PubMed2005

Effects of age and dopamine D2L receptor-deficiency on motor and learning functions.

Decreases in the activity or density of dopamine D2 receptor (D2R) have been associated with age-related changes and neurodegenerative diseases such as Parkinson's disease. There are two isoforms of the D2R, termed the D2 long receptor (D2LR) and D2 short receptor (D2SR). To study the function of these two isoforms and their role in aging, we generated mice selectively lacking D2LR (D2L-/-). Here, we showed that middle-aged (12 months) to aged wild-type (WT) mice (22-24 months) displayed significantly lower levels of motor and learning functions than young WT mice (3 months). Interestingly, young D2L-/- mice (which still express D2SR) showed behavioral deficits similar to aged WT mice. It is possible that deletion of the D2LR might facilitate the aging process in mice. Our results also suggest that a deterioration of the D2LR (but not D2SR) system during aging may account, at least in part, for the motor and learning deficits exhibited in aged WT mice. We also showed that the critical age at which significant reduction in behavior occurred varied among different behaviors. Defining the age-related critical periods and understanding the role of the two D2R isoforms in aging may facilitate the development of new strategies for delaying or ameliorating age-related motor and learning impairments.

Age Factors↗
PubMed2005

Opposing roles of transient and prolonged expression of p25 in synaptic plasticity and hippocampus-dependent memory.

While deregulation of cyclin-dependent kinase 5 (Cdk5) has been implicated in neurodegenerative diseases, its precise role in synaptic plasticity and memory remains elusive. Proteolytic cleavage of p35, a regulatory subunit of Cdk5, by calpain results in the generation of the truncated p25 protein, which causes hyperactivation of Cdk5. Using region-specific and inducible transgenic mice, we show that transiently increased p25 expression in the hippocampus enhanced long-term potentiation (LTP) and facilitated hippocampus-dependent memory. Moreover, p25 expression increased the number of dendritic spines and synapses. Importantly, enhanced memory achieved by a transient expression of p25 followed by its repression did not cause neurodegeneration. In contrast, prolonged p25 production caused severe cognitive deficits, which were accompanied by synaptic and neuronal loss and impaired LTP. Our data suggest a role for p25 in synaptic plasticity, synaptogenesis, learning, and memory and provide a model whereby deregulation of a plasticity factor can contribute to neurodegeneration.

Animals↗
PubMed2004

The role of stimulus ambiguity and movement in spatial navigation: a multiple memory systems analysis of location discrimination.

This paper reviews recent findings about how rats navigate by learning to discriminate among locations. The assumption underlying the experiments and their interpretation is that the information required to do this is learned by three independent, parallel memory systems. One system processes cognitive information (or "knowledge"), a second system processes reinforced stimulus-response associations and a third processes Pavlovian conditioned responses in the form of stimulus-affect associations. The information stored in each system produces behavior that, in some cases, results in a location discrimination. The present experiments focus on three factors that influence what each system learns and whether the resulting memory produces behavior that results in a location discrimination. One factor is whether the locations to be discriminated can be identified by unique, unambiguous stimuli or whether they are ambiguously associated with the same stimuli. The second factor is whether the stimuli are observed passively or whether the rats move among them, voluntarily or involuntarily. The third factor is whether or not the rats perform specific reinforced responses in the presence of the stimuli. Instances of co-operative behavioral outputs from memory systems that facilitate location discriminations and of competitive outputs that impede discriminations are described.

Animals↗
PubMed2005

In vivo inhibition of hippocampal Ca2+/calmodulin-dependent protein kinase II by RNA interference.

Hippocampal alpha-Ca2+/calmodulin-dependent protein kinase II (alpha-CaMKII) has been implicated in spatial learning, neuronal plasticity, epilepsy, and cerebral ischemia. In the present study, an adeno-associated virus (AAV) vector was designed to express green fluorescent protein (GFP) from the CBA promoter and a small hairpin RNA targeting alpha-CaMKII (AAV-shCAM) driven from the U6 promoter. The AAV-shCAM or control vector was microinfused into the rat hippocampus and behavioral testing conducted 19-26 days following surgery. Expression of the marker gene and alpha-CaMKII was evaluated 31 days following AAV infusion. GFP expression was localized to the hippocampus and extended +/-2 mm rostral and caudal from the injection site. Hippocampal alpha-CaMKII was significantly reduced following AAV-shCAM treatment as demonstrated using immunohistochemical and Western analysis. This suppression of alpha-CaMKII was associated with changes in exploratory behavior (open field task) and impaired place learning (water maze task). These results demonstrate the efficacy of a viral-based delivered shRNA to produce gene suppression in a specific circuit of the brain.

Animals↗
PubMed1977

Further studies of tactile perception and motor coordination in agenesis of the corpus callosum.

A 12-year-old female with total agenesis of the corpus callosum has been tested on several tasks involving tactile perception and motor coordination. Her performance has been compared with a group of normals of the same age and sex and a group of subjects matched for age, sex and I.Q. On 3 of the bimanual motor coordination tasks the acallosal's performance was not clearly distinguishable from the control's. She was, however, slower than the controls on the pegboard task. On a transfer of training task (formboard) the acallosal was slower than normals and did not manifest transfer. However, transfer of training was shown on a maze-learning task. No deficit was found in the ability to tactually cross-identify objects, but a deficit in tactile cross-localization was evidenced.

Adolescent↗
PubMed1984

The effect of the beta-adrenergic receptor antagonist, propranolol, on the cerebral spread of a memory trace in mice.

Bi-temporal injections of puromycin that primarily affect the hippocampal-entorhinal areas consistently induce amnesia of aversive maze-learning in mice for 3 days after training but are consistently ineffective if given 6 or more days after training. At these later times, additional puromycin sites covering widespread areas of the forebrain are necessary to induce amnesia. Consistent with other evidence, these observations are interpreted to indicate that the locus of the memory trace becomes more widespread during the 6-day period. A single subcutaneous injection of (-)-propranolol (50 micrograms/kg) given either before or 2 days after training suppressed engram spread for 60-90 days, at which time engram spread spontaneously occurred. This effect of propranolol was stereospecific. Suppression of engram spread persisted for a prolonged period in spite of the rapid recovery (about 4 hr), following treatment, of the normal level of specific binding of 3H-dihydroalprenolol in membrane preparations of the cerebral hemispheres and of 125I-pindolol in selected areas of the forebrain, diencephalon and brainstem.

Animals↗
PubMed2003

The hyperpolarization-activated HCN1 channel is important for motor learning and neuronal integration by cerebellar Purkinje cells.

In contrast to our increasingly detailed understanding of how synaptic plasticity provides a cellular substrate for learning and memory, it is less clear how a neuron's voltage-gated ion channels interact with plastic changes in synaptic strength to influence behavior. We find, using generalized and regional knockout mice, that deletion of the HCN1 channel causes profound motor learning and memory deficits in swimming and rotarod tasks. In cerebellar Purkinje cells, which are a key component of the cerebellar circuit for learning of correctly timed movements, HCN1 mediates an inward current that stabilizes the integrative properties of Purkinje cells and ensures that their input-output function is independent of the previous history of their activity. We suggest that this nonsynaptic integrative function of HCN1 is required for accurate decoding of input patterns and thereby enables synaptic plasticity to appropriately influence the performance of motor activity.

Action Potentials↗
PubMed2000

Is the avian hippocampus a functional homologue of the mammalian hippocampus?

The effects of hippocampal lesions on the processing and retention of visual and spatial information in birds and mammals is reviewed. Both birds and mammals with damage to the hippocampus are severely impaired on a variety of spatial tasks, such as navigation, maze learning, and the retention of spatial information. In contrast, both birds and mammals with damage to the hippocampus are not impaired on a variety of visual tasks, such as delayed matching-to-sample, concurrent discrimination, or retention of a visual discrimination. In addition, both birds and mammals with hippocampal damage display impairments in the acquisition of an autoshaped response, as well as alterations in response suppression. These findings suggest that the avian hippocampus is a functional homologue of the mammalian hippocampus, and that in both birds and mammals the hippocampus is important for the processing and retention of spatial, rather than purely visual information.

Animals↗
PubMed1999

Further phenotypical characterisation of two substrains of C57BL/6J inbred mice differing by a spontaneous single-gene mutation.

Males from two substrains of C57BL/6J mice, which have been found to differ for open-field exploration, radial-maze learning, and the sizes of their hippocampal intra- and infra-pyramidal mossy fibre (IIPMF) terminal fields, were compared for offensive aggression, thermoregulatory nest-building, and their behaviour in the Light-Dark choice test. The substrain with the smaller IIPMF showed higher aggression and more nest-building behavior than the one with the larger IIPMF, whereas only tentative differences were found in the Light Dark choice test. These findings confirm and expand on previously found genetic links between the IIPMF and behaviours in mice. These substrains provide a powerful tool to localise the gene involved and subsequently investigate the pathway leading from gene to behaviour.

Animals↗
PubMed2000

Site-directed antisense oligonucleotide decreases the expression of amyloid precursor protein and reverses deficits in learning and memory in aged SAMP8 mice.

beta amyloid protein (Abeta) is a 40-43 amino acid peptide derived from amyloid precursor protein (APP). Abeta has been implicated as a cause of Alzheimer's disease (AD). Mice with spontaneous or transgenic overexpression of APP show the histologic hallmarks of AD and have impairments in learning and memory. We tested whether antisense phosphorothiolated oligonucleotides (AO) directed at the Abeta region of the APP gene given with or without antibody directed at Abeta could reverse the elevated protein levels of APP and the behavioral impairments seen in SAMP8 mice, a strain which spontaneously overexpresses APP. We found that intracerebroventricular (ICV) administration of antibody with either of two AOs directed at the midregion of Abeta improved acquisition and retention in a footshock avoidance paradigm, whereas two AOs directed more toward the C-terminal, a random AO, and vehicle were without effect. Three injections of the more potent AO given without antibody reduced APP protein levels by 43-68% in the amygdala, septum, and hippocampus. These results show that AO directed at the Abeta region of APP can reduce APP levels in the brain and reverse deficits in learning and memory.

Age Factors↗
PubMed1999

Brain renin angiotensin system (RAS) in stress-induced analgesia and impaired retention.

Physiological stress is known to produce analgesia and memory disruption. Brain renin angiotensin system (RAS) has been reported to participate in stress response and plays a role in the processing of sensory information. Angiotensin receptors (AT), particularly AT1 subtypes have been reported to be distributed in brain areas that are intimately associated with stress response. The purpose of present study was to examine the modulation of AT1 receptor in the immobilization stress and angiotensin II (AngII)-induced analgesia and impaired retention, and to determine whether resultant behavioral changes involve common sensory signals. Result of present experiments showed that immobilization stress in mice and rats, and intracerebroventricular (ICV) administration of AngII (10 and 20 ng) in rats produced an increase in tail-flick latency. Similarly, post training administration of AngII or immobilization stress produced impairment of retention tested on plus-maze learning and on passive avoidance step-down task. Both these responses were sensitive to reversal by prior treatment with losartan (10 and 20 mg/kg), an AT1 AngII receptor antagonist. On the other hand, naloxone, an opiate antagonist preferentially attenuated the stress and AngII-induced analgesia and retention deficit induced by immobilization stress, but failed to reverse the AngII induced retention deficit. These results suggest immobilization stress-induced analgesia and impaired retention involves the participation of brain RAS. Further, failure of naloxone to reverse AngII-induced retention impairment shows. AngII-induced behavioral changes are under control of different sensory inputs.

Angiotensin II↗
PubMed1998

Behavioural, physiological and morphological analysis of a line of apolipoprotein E knockout mouse.

Using apolipoprotein E knockout mice derived from the Maeda source [Piedrahita J. A. et al. (1992) Proc. natn. Acad Sci. US.A. 89, 4471 4475], we have studied the influence of apolipoprotein E gene deletion on normal CNS function by neurological tests and water maze learning, hippocampal ultrastructure assessed by quantitative immunocytochemistry and electron microscopy, CNS plasticity, i.e. hippocampal long-term potentiation and amygdaloid kindling, and CNS repair, i.e. synaptic recovery in the hippocampus following deafferentation. In each study there was little difference between the apolipoprotein E knockout mice and wild-type controls of similar age and genetic background. Apolipoprotein E knockout mice aged eight months demonstrated accurate spatial learning and normal neurological function. Synaptophysin and microtubule-associated protein 2 immunohistochemistry and electron microscopic analysis of these animals revealed that the hippocampal synaptic and dendritic densities were similar between genotypes. The induction and maintenance of kindled seizures and hippocampal long-term potentiation were indistinguishable between groups. Finally, unilateral entorhinal cortex lesions produced a marked loss of hippocampal synaptophysin immunoreactivity in both groups and a marked up-regulation of apolipoprotein E in the wild-type group. Both apolipoprotein E knockout and wild-type groups showed immunohistochemical evidence of reactive synaptogenesis, although the apolipoprotein E knockout group may have initially shown greater synaptic loss. It is suggested that either apolipoprotein E is of no importance in the maintenance of synaptic integrity and in processes of CNS plasticity and repair, or more likely, alternative (apolipo)proteins may compensate for the loss of apolipoprotein E in the knockout animals.

Animals↗