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FEF inactivation with improved optogenetic methods.

ABSTRACT: Optogenetic methods have been highly effective for suppressing neural activity and modulating behavior in rodents, but effects have been much smaller in primates, which have much larger brains. Here, we present a suite of technologies to use optogenetics effectively in primates and apply these tools to a classic question in oculomotor control. First, we measured light absorption and heat propagation in vivo, optimized the conditions for using the red-light-shifted halorhodopsin Jaws in primates, and developed a large-volume illuminator to maximize light delivery with minimal heating and tissue displacement. Together, these advances allowed for nearly universal neuronal inactivation across more than 10 mm³ of the cortex. Using these tools, we demonstrated large behavioral changes (i.e., up to several fold increases in error rate) with relatively low light power densities (?100 mW/mm²) in the frontal eye field (FEF). Pharmacological inactivation studies have shown that the FEF is critical for executing saccades to remembered locations. FEF neurons increase their firing rate during the three epochs of the memory-guided saccade task: visual stimulus presentation, the delay interval, and motor preparation. It is unclear from earlier work, however, whether FEF activity during each epoch is necessary for memory-guided saccade execution. By harnessing the temporal specificity of optogenetics, we found that FEF contributes to memory-guided eye movements during every epoch of the memory-guided saccade task (the visual, delay, and motor periods).

SUBMITTER: Acker L

PROVIDER: S-EPMC5135345 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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FEF inactivation with improved optogenetic methods.

Acker Leah L Pino Erica N EN Boyden Edward S ES Desimone Robert R

Proceedings of the National Academy of Sciences of the United States of America 20161102 46

Optogenetic methods have been highly effective for suppressing neural activity and modulating behavior in rodents, but effects have been much smaller in primates, which have much larger brains. Here, we present a suite of technologies to use optogenetics effectively in primates and apply these tools to a classic question in oculomotor control. First, we measured light absorption and heat propagation in vivo, optimized the conditions for using the red-light-shifted halorhodopsin Jaws in primates, ...[more]

PMID: 27807140

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Project description:BackgroundReference equations for forced expiratory flow at 50% and 75% of forced vital capacity (FVC) (FEF50 and FEF75) in the Chinese population are lacking. It is of great importance to establish equations covering most age groups and to study their applicability in clinical practice.MethodsUsing the lambda-mu-sigma (LMS) method, reference equations for FEF50 and FEF75 were constructed based on pulmonary function data from healthy subjects collected from January 2007 to June 2010 at 24 centers throughout China. Differences between the established equations and extraneous equations were compared using standardized means (Z values) and percentage errors (PE). The proportion of small airway dysfunction (SAD) defined by the present equations was calculated. The Fisher precision probability test and the Mann-Whitney test were used to analyze the magnitude of changes in small and large airway indices after bronchodilator inhalation in patients with suspected asthma and chronic obstructive pulmonary disease (COPD).ResultsReference equations for FEF50 and FEF75 were established based on data from 7,115 healthy individuals (aged 4 to 80 years, 50.9% female, height between 95 and 190 cm). The present equations (all Z values were -0.0 and PE ranged from 2.0% to 4.2%) showed advantages over the European Community for Steel and Coal (ECSC) equations in 1993 (with Z values ranging from -0.7 to -0.2 and PE ranged from -23.4% to -4.5%). A total of 4,356 patients with suspected asthma (51.1% female; a mean age of 45.4 years) and 6,558 patients with suspected COPD (10.1% female; a mean age of 65.0 years) were included. The present equations defined 95.7% and 99.9% of SAD in these patients. After bronchodilator inhalation, greater mean improvement rates in small airway indices were observed both in patients with suspected asthma [mean ± standard deviation (SD) =48%±47%] and in patients with suspected COPD (mean ± SD =20%±30%) (P<0.05).ConclusionsThe reference equations for FEF50 and FEF75 established in this study should be considered for use in China. Further studies are needed to validate their value in the diagnosis of some chronic respiratory diseases.

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FEF inactivation with improved optogenetic methods.

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FEF inactivation with improved optogenetic methods.

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