BDNF val66met polymorphism is associated with modified experience-dependent plasticity in human motor cortex.

Motor training can induce profound physiological plasticity within primary motor cortex, including changes in corticospinal output and motor map topography. Using transcranial magnetic stimulation, we show that training-dependent increases in the amplitude of motor-evoked potentials and motor map reorganization are reduced in healthy subjects with a val66met polymorphism in the brain-derived neurotrophic factor gene (BDNF), as compared to subjects without the polymorphism. The results suggest that BDNF is involved in mediating experience-dependent plasticity of human motor cortex

The Vermicelli and Capellini Handling Tests: Simple quantitative measures of dexterous forepaw function in rats and mice

Previous characterizations of rodent eating behavior have revealed that they use coordinated forepaw movements to manipulate food pieces. We have extended upon this work to develop a simple quantitative measure of forepaw dexterity that is sensitive to lateralized impairments and age-dependent changes. Rodents learn skillful forepaw and digit movements to manage thin pasta pieces, which they eagerly consume. We have previously described methods for quantifying vermicelli handling in rats and showed that the measures are very sensitive to forelimb impairments resulting from unilateral ischemic lesions, middle cerebral artery occlusions and unilateral striatal dopamine depletion [Allred, R.P., Adkins, D.L., Woodlee, M.T., Husbands, L.C., Maldonado M.A., Kane, J.R., Schallert, T. & Jones, T.A. The Vermicelli Handling Test: a simple quantitative measure of dexterous forepaw function in rats. J. Neurosci. Methods 170, 229-244 (2008)]. Here we present a more detailed protocol for this test in rats and compare it with a newly developed version for mice, the Capellini Handling Test. Rats and mice are videotaped while handling short lengths of uncooked vermicelli or capellini pasta, respectively, with a camera positioned to optimize the view of paw movements. Slow motion video playback allows for the identification of forepaw adjustments, defined as any distinct removal and replacement of the paw, or of any number of digits, on the pasta piece after eating commences. Forepaw adjustments per piece are averaged over trials per each testing session. Repeated testing permits sensitive quantitative analysis of changes in forepaw dexterity over time. Protocols for pre-testing habituation and handling practice, as well as procedures for characterizing atypical handling patterns, are described. Because rats and mice perform the pasta handling tests slightly differently, species-specific differences in administration and scoring of these tests are highlighted. All animal use was in accordance with protocols approved by the University of Texas at Austin Animal Care and Use Committee

Systematic assessment of training-induced changes in corticospinal output to hand using frameless stereotaxic transcranial magnetic stimulation.

Measuring changes in the characteristics of corticospinal output has become a critical part of assessing the impact of motor experience on cortical organization in both the intact and injured human brain. In this protocol we describe a method for systematically assessing training-induced changes in corticospinal output that integrates volumetric anatomical MRI with transcranial magnetic stimulation (TMS). A TMS coil is sited to a target grid superimposed onto a 3D MRI of cortex using a stereotaxic neuronavigation system. Subjects are then required to exercise the first dorsal interosseus (FDI) muscle on two different tasks for a total of 30 min. The protocol allows for reliably and repeatedly detecting changes in corticospinal output to FDI muscle in response to brief periods of motor training

RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy

<p>Abstract</p> <p>Background</p> <p>To study the dynamics of wild-type and drug-resistant HIV-1 RT variants, we developed a methodology that follows the fates of individual genomes over time within the viral quasispecies. Single genome sequences were obtained from 3 pigtail macaques infected with a recombinant simian immunodeficiency virus containing the RT coding region from HIV-1 (RT-SHIV) and treated with short-course efavirenz monotherapy 13 weeks post-infection followed by daily combination antiretroviral therapy (ART) beginning at week 17. Bioinformatics tools were constructed to trace individual genomes from the beginning of infection to the end of the treatment.</p> <p>Results</p> <p>A well characterized challenge RT-SHIV inoculum was used to infect three monkeys. The RT-SHIV inoculum had 9 variant subpopulations and the dominant subpopulation accounted for 80% of the total genomes. In two of the three monkeys, the inoculated wild-type virus was rapidly replaced by new wild type variants. By week 13, the original dominant subpopulation in the inoculum was replaced by new dominant subpopulations, followed by emergence of variants carrying known NNRTI resistance mutations. However, during ART, virus subpopulations containing resistance mutations did not outgrow the wide-type subpopulations until a minor subpopulation carrying linked drug resistance mutations (K103N/M184I) emerged. We observed that persistent viremia during ART is primarily made up of wild type subpopulations. We also found that subpopulations carrying the V75L mutation, not known to be associated with NNRTI resistance, emerged initially in week 13 in two macaques. Eventually, all subpopulations from these two macaques carried the V75L mutation.</p> <p>Conclusion</p> <p>This study quantitatively describes virus evolution and population dynamics patterns in an animal model. The fact that wild type subpopulations remained as dominant subpopulations during ART treatment suggests that the presence or absence of at least some known drug resistant mutations may not greatly affect virus replication capacity <it>in vivo</it>. Additionally, the emergence and prevalence of V75L indicates that this mutation may provide the virus a selective advantage, perhaps escaping the host immure system surveillance. Our new method to quantitatively analyze viral population dynamics enabled us to observe the relative competitiveness and adaption of different viral variants and provided a valuable tool for studying HIV subpopulation emergence, persistence, and decline during ART.</p

Brain plasticity and genetic factors.

Brain plasticity refers to changes in brain function and structure that arise in a number of contexts. One area in which brain plasticity is of considerable interest is recovery from stroke, both spontaneous and treatment-induced. A number of factors influence these poststroke brain events. The current review considers the impact of genetic factors. Polymorphisms in the human genes coding for brain-derived neurotrophic factor (BDNF) and apolipoprotein E (ApoE) have been studied in the context of plasticity and/or stroke recovery and are discussed here in detail. Several other genetic polymorphisms are indirectly involved in stroke recovery through their modulating influences on processes such as depression and pharmacotherapy effects. Finally, new genetic polymorphisms that have not been studied in the context of stroke are proposed as new directions for study. A better understanding of genetic influences on recovery and response to therapy might allow improved treatment after stroke

BDNF val66met polymorphism influences motor system function in the human brain.

Brain-derived neurotrophic factor (BDNF) is important to brain functions such as plasticity and repair. A single nucleotide polymorphism for this growth factor, val(66)met, is common and associated with decreased activity-dependent BDNF release. The current study evaluated the effects of this polymorphism in relation to human brain motor system function, short-term plasticity, and learning. Functional magnetic resonance imaging (fMRI) scanning during right index finger movement (n = 24) identified activation in a broad sensorimotor network. However, subjects with the polymorphism showed smaller activation volume within several brain regions as compared with subjects without the polymorphism. Repeat fMRI after 25 min of right index finger training found that the 2 genotype groups modulated brain activation differently. In several brain regions, subjects with the polymorphism showed greater activation volume reduction, whereas subjects without the polymorphism showed greater activation volume expansion. On a driving-based motor learning task (independent cohort, n = 29), subjects with the polymorphism showed greater error during short-term learning and poorer retention over 4 days, relative to subjects without the polymorphism. The presence of this BDNF polymorphism is associated with differences in brain motor system function, altered short-term plasticity, and greater error in short-term motor learning. The broader implications of these findings are considered