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R Paylor

Publications and source records attributed to R Paylor.

50 records · Page 3Linked to original sources
PubMed1992

Impaired spatial learning in alpha-calcium-calmodulin kinase II mutant mice.

Although long-term potentiation (LTP) has been studied as the mechanism for hippocampus-dependent learning and memory, evidence for this hypothesis is still incomplete. The mice with a mutation in the alpha-calcium-calmodulin-dependent kinase II (alpha-CaMKII), a synaptic protein enriched in the hippocampus, are appropriate for addressing this issue because the hippocampus of these mice is deficient in LTP but maintains intact postsynaptic mechanisms. These mutant mice exhibit specific learning impairments, an indication that alpha-CaMKII has a prominent role in spatial learning, but that it is not essential for some types of non-spatial learning. The data considerably strengthen the contention that the synaptic changes exhibited in LTP are the basis for spatial memory.

Animals↗
PubMed1991

Acute phorbol ester treatment improves spatial learning performance in rats.

Recent findings have lead researchers to speculate that hippocampal protein kinase C (PKC) in rodents is involved in spatial learning and memory. The purpose of this study was to determine if treating rats with a compound known to increase PKC activity would improve performance in a task that requires spatial learning processes. Rats were treated with a single intracerebroventricular injection of a phorbol ester, phorbol 12,13-dibutyrate (PDBu) that is known to increase PKC activity and then tested on the hidden-platform version of the Morris water taks. Results showed that PDBu-treated subjects' ability to learn to locate the escape platform was better than controls. In addition, PDBu-treated subjects showed signs of having remembered the location of the platform better than controls when tested 24 h later. These results support a role of brain PKC in processes required to learn the Morris water task.

Animals↗
PubMed1990

Cholinergic receptor blockade can impair the rat's performance on both the place learning and cued versions of the Morris water task: the role of age and pool wall brightness.

It is known that the administration of a cholinergic receptor blocker impairs the rat's performance on the place learning version of the Morris water task. We confirm this finding but in addition report that animals receiving the cholinergic antagonist, scopolamine hydrobromide, are significantly impaired on the cued platform version of the Morris water task. This latter result, however, is dependent on both the age of the subject and the training context. Weanling animals were more impaired on the cued platform task than were adult animals, and the magnitude of the impairment was much larger when animals were trained in a pool with a gray interior wall than when the pool wall was white. Our findings suggest that the influence of cholinergic systems on performance in the Morris task extend beyond their contribution to place learning and memory processes. We suggest that functional central cholinergic systems also contribute to the processes that enable the animal to inhibit behaviors that are incompatible with the requirements of the task.

Age Factors↗
PubMed1990

The cholinergic agent physostigmine enhances short-term-memory-based performance in the developing rat.

There are age-related differences in the rat's short-term memory processes. Rats 24-25 days old are 90% correct when the delay interval separating the forced run and choice run of a trial is either 10 or 30 s, but they perform at chance when the delay interval is 60 s. In contrast, the choice performance of 30-day-old rats remains constant across all delay intervals. It is reported that the cholinergic agent physostigmine dramatically improved the short-term-memory-based performance of rats 24-25 days old such that they displayed no loss in choice accuracy even when the delay interval was 60 s. No such enhanced performance was seen in rats treated with neostigmine, a peripherally acting anticholinesterase. The results support the hypothesis that postnatal maturational differences in central cholinergic systems may contribute to age-related differences in short-term memory.

Age Factors↗
PubMed1987

Development of interocular equivalence of place learning in the rat requires convergence sites established prior to training.

Interocular equivalence for spatial-navigation learning requires that the neural pathways originating in each eye converge on common memory sites. Rats fail to display interocular equivalence if they are trained and tested on the Morris (1981) place-navigation task when they are 22 days old, but they succeed if they are trained and tested when they are 28 days old (Rudy & Stadler-Morris, 1987). This delay suggests that there is a period in development when the interhemispheric connections necessary for convergence are immature and rats behave temporarily as split-brain organisms. In the present experiment, rats completed training when they were 22 days old but were not tested for interocular equivalence until they were 28 days old. Nevertheless, these subjects failed to demonstrate equivalence. Thus, for interocular equivalence to be observed, the neural pathways from each eye must converge on common neural sites that are functional at the time the memory representation is established.

Animals↗
PubMed1987

Effects of intravitreal injection of fluorosilicone oil after vitrectomy in the rabbit eye.

Because fluorosilicone oil is heavier than silicone oil, it may be superior in the therapy of proliferative vitreoretinopathy. To evaluate the ocular toxicity of fluorosilicone oil we performed pars plana lentectomy and vitrectomy on 14 rabbit eyes and injected approximately 1.5 mL of the oil (viscosity 10,000 centistoke) into the vitreous chamber of 10. No clinical or histologic evidence of toxic ocular effects was noted up to 2 months after the procedure.

Animals↗
PubMedDate not supplied

Mice lacking the ERK1 isoform of MAP kinase are unimpaired in emotional learning.

The extracellular signal-regulated kinases (ERKs) are members of the mitogen-activated protein kinase (MAPK) superfamily of enzymes and have recently garnered considerable attention in the field of learning and memory. ERK activation has been shown to be required for the induction of long-term potentiation (LTP) in the rat hippocampus and for the formation of associative and spatial memories in both the rat and the mouse. However, the individual roles for the two isoforms of ERK have yet to be deciphered. To investigate the specific contribution of the ERK1 (p44) isoform of MAPK to mammalian learning, we performed a general behavioral and physiological characterization of mice lacking the ERK1 gene. The ERK1-null animals demonstrated significantly higher levels of activity in the open field test. However, we observed no other discernible deficits in the ERK1 knockout mice in our behavioral testing. Specifically, no differences were observed in the acquisition or retention (24 h and 2 wk after training) of either contextual or cue fear conditioning between the ERK1(-/-) and their wild-type littermate controls. In addition, no learning phenotype was observed in the passive avoidance test. When hippocampal slices were analyzed, we found no deficits in baseline synaptic transmission or in tetanus-induced LTP in hippocampal area CA1. We found no apparent compensatory changes in the expression of ERK2 (p42 MAPK). We conclude that hippocampus- and amygdala-dependent emotional learning does not depend critically on the activity of ERK1.

Animals↗
PubMedDate not supplied

A necessity for MAP kinase activation in mammalian spatial learning.

Although the biochemical mechanisms underlying learning and memory have not yet been fully elucidated, mounting evidence suggests that activation of protein kinases and phosphorylation of their downstream effectors plays a major role. Recent findings in our laboratory have shown a requirement for the mitogen-activated protein kinase (MAPK) cascade in hippocampal synaptic plasticity. Therefore, we used an inhibitor of MAPK activation, SL327, to test the role of the MAPK cascade in hippocampus-dependent learning in mice. SL327, which crosses the blood-brain barrier, was administered intraperitoneally at several concentrations to animals prior to cue and contextual fear conditioning. Administration of SL327 completely blocked contextual fear conditioning and significantly attenuated cue learning when measured 24 hr after training. To determine whether MAPK activation is required for spatial learning, we administered SL327 to mice prior to training in the Morris water maze. Animals treated with SL327 exhibited significant attenuation of water maze learning; they took significantly longer to find a hidden platform compared with vehicle-treated controls and also failed to use a selective search strategy during subsequent probe trials in which the platform was removed. These impairments cannot be attributed to nonspecific effects of the drug during the training phase; no deficit was seen in the visible platform task, and injection of SL327 following training produced no effect on the performance of these mice in the hidden platform task. These findings indicate that the MAPK cascade is required for spatial and contextual learning in mice.

Animals↗
PubMedDate not supplied

Impaired learning and motor behavior in heterozygous Pafah1b1 (Lis1) mutant mice.

Heterozygous mutation or deletion of Pafab1b1 (LIS1) in humans is associated with syndromes with type 1 lissencephaly, a severe brain developmental disorder resulting from abnormal neuronal migration. We have created Lis1 heterozygous mutant mice by gene targeting. Heterozygous mutant mice are viable and fertile, but display global organizational brain defects as a result of impaired neuronal migration. To assess the functional impact of the mutation, Lis1 heterozygous mice and their wild-type littermates were evaluated on a wide variety of behavioral tests. Lis1 mutant mice displayed abnormal hindpaw clutching responses and were impaired on a rotarod test. Lis1 heterozygous mice were also impaired in the spatial learning version of the Morris water task. Impaired motor behavior and spatial learning and memory in Lis1 mutant mice indicates that impaired neuronal migration can have functional effects on complex behavioral responses. The behavioral findings also support the use of the Lis1 mutant mice as a model from human type 1 lissencephaly.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMedDate not supplied

Alpha7 nicotinic receptor subunits are not necessary for hippocampal-dependent learning or sensorimotor gating: a behavioral characterization of Acra7-deficient mice.

The alpha7 nicotinic acetylcholine receptor (nAChR) subunit is abundantly expressed in the hippocampus and contributes to hippocampal cholinergic synaptic transmission suggesting that it may contribute to learning and memory. There is also evidence for an association between levels of alpha7 nAChR and in sensorimotor gating impairments. To examine the role of alpha7 nAChRs in learning and memory and sensorimotor gating, Acra7 homozygous mutant mice and their wild-type littermates were tested in a Pavlovian conditioned fear test, for spatial learning in the Morris water task, and in the prepulse inhibition paradigm. Exploratory activity, motor coordination, and startle habituation were also evaluated. Acra7 mutant mice displayed the same levels of contextual and auditory-cue condition fear as wild-type mice. Similarly, there were no differences in spatial learning performance between mutant and wild-type mice. Finally, Acra7 mutant and wild-type mice displayed similar levels of prepulse inhibition. Other behavioral responses in Acra7 mutant mice were also normal, except for an anxiety-related behavior in the open-field test. The results of this study show that the absence of alpha7 nAChRs has little impact on normal, base-line behavioral responses. Future studies will examine the contribution of alpha7 nAChR to the enhancement of learning and sensorimotor gating following nicotine treatments.

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PubMedDate not supplied

Automated measurement of mouse freezing behavior and its use for quantitative trait locus analysis of contextual fear conditioning in (BALB/cJ x C57BL/6J)F2 mice.

The most commonly measured mouse behavior in fear conditioning tests is freezing. A technical limitation, particularly for genetic studies, is the method of direct observation used for quantifying this response, with the potential for bias or inconsistencies. We report the use of a computerized method based on latency between photobeam interruption measures as a reliable scoring criterion in mice. The different computer measures obtained during contextual fear conditioning tests showed high correlations with hand-scored freezing; r values ranged from 0.87 to 0.94. Previously reported strain differences between C57BL/6J and DBA/2J in context-dependent fear conditioning were also detected by the computer-based system. In addition, the use of computer-scored freezing of 199 (BALB/cJ x C57BL/6J)F2 mice enabled us to detect a suggestive gender-dependent chromosomal locus for contextual fear conditioning on distal chromosome 8 by QTL analysis. Automation of freeze scoring would significantly increase efficiency and reliability of this learning and memory test.

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