Protease-activated receptor-1 (PAR1) is an unusual G-protein coupled receptor (GPCR) that is activated through proteolytic cleavage by extracellular serine proteases. While previous work has shown that inhibiting PAR1 activation is neuroprotective in models of ischemia, traumatic injury, and neurotoxicity, surprisingly little is known about PAR1’s contribution to normal brain function. Here we used PAR1 −/− mice to investigate the contribution of PAR1 function to memory formation and synaptic function. We demonstrate that PAR1 −/− mice have deficits in hippocampus-dependent memory. We also show that while PAR1 −/− mice have normal baseline synaptic transmission at Schaffer collateral-CA1 synapses, they exhibit severe deficits in N-methyl-D-aspartate receptor (NMDAR)-dependent long-term potentiation (LTP). Mounting evidence indicates that activation of PAR1 leads to potentiation of NMDAR-mediated responses in CA1 pyramidal cells. Taken together, this evidence and our data suggest an important role for PAR1 function in NMDAR-dependent processes subserving memory formation and synaptic plasticity.
Objective-Evaluate psychometric properties of the Functional Arm Activity Behavioral Observation System for measuring hemiparetic arm use.Participants and Measures-All participants acquired their brain injury > 1-year prior to study entry; most had mild-to-moderate upper-extremity hemiparesis. In Study 1, nine stroke survivors wore accelerometers and were videotaped for 15 minutes in the hospital or at home after they were asked to behave as usual. In Study 2, one traumatic brain injury and eight stroke survivors wore accelerometers and were videotaped at home for 3 days with a motion-triggered camera. Observers independently rated 15-minute segments of the Study 1 and 2 videotapes in 2-s blocks with a 4-step arm-activity coding scheme.Results-Inter-rater reliability was excellent; the mean Cohen's κ in each study was ≥ .84. For data from both studies combined, validity was supported by a strong correlation between amount of hemiparetic arm functional activity, as determined by the observers, and the ratio of hemiparetic to other arm movement, as determined by accelerometry. Conclusion-FAABOSreliably and validly quantifies amount of spontaneous hemiparetic arm activity outside the laboratory. Keywordsarm; observation; rehabilitation; treatment outcome; stroke Several bodies of evidence suggest that under certain conditions actual use of an upperextremity departs markedly from the severity of impairment after neurological injury (e.g., see review by Animal studies directed by E. Taub have shown that monkeys that have had surgery to abolish all sensation from a forelimb typically never use this limb again even though they recover considerable ability to control movements of the deafferented limb 8-24 weeks after surgery. The monkeys do not use their deafferented forelimb even though they can 8-24 weeks after surgery because when the animals attempt to use that forelimb Correspondence concerning this article should be addressed to Gitendra Uswatte, Ph.D., Department of Psychology, UAB, 1530 3rd Ave S., CH415, Birmingham, AL 35294. guswatte@uab.edu. Publisher's Disclaimer: The following manuscript is the final accepted manuscript. It has not been subjected to the final copyediting, fact-checking, and proofreading required for formal publication. It is not the definitive, publisher-authenticated version. The American Psychological Association and its Council of Editors disclaim any responsibility or liabilities for errors or omissions of this manuscript version, any version derived from this manuscript by NIH, or other third parties. The published version is available at www.apa.org/journals/rep. This paper presents inter-rater reliability and convergent validity for the Functional Arm Activity Behavioral Observation System (FAABOS), which quantifies amount of moreimpaired arm function in daily life from random samples of video recordings from stroke and TBI survivors' homes. Results are presented from two separate groups of participants (Study 1 and 2), who were videotaped in different contexts and rated by...
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