ABSTRACT
Alterations in our environment require us to learn or alter motor skills to remain efficient. Also, damage or injury may require the relearning of motor skills. Two types have been identified: movement adaptation and motor sequence learning. Doyonet al. (2003, Distinct contribution of the cortico-striatal and cortico-cerebellar systems to motor skill learning. Neuropsychologia, 41(3), 252-262) proposed a model to explain the neural mechanisms related to adaptation (cortico-cerebellar) and motor sequence learning (cortico-striatum) tasks. We hypothesized that medial frontal negativities (MFNs), event-related electrocortical responses including the error-related negativity (ERN) and correct-response-related negativity (CRN), would be trait biomarkers for skill in motor sequence learning due to their relationship with striatal neural generators in a network involving the anterior cingulate and possibly the supplementary motor area. We examined 36 participants' improvement in a motor adaptation and a motor sequence learning task and measured MFNs elicited in a separate Spatial Stroop (conflict) task. We found both ERN and CRN strongly predicted performance improvement in the sequential motor task but not in the adaptation task, supporting this aspect of the Doyon model. Interestingly, the CRN accounted for additional unique variance over the variance shared with the ERN suggesting an expansion of the model.
Subject(s)
Adaptation, Physiological/physiology , Evoked Potentials/physiology , Frontal Lobe/physiology , Learning/physiology , Motor Skills/physiology , Adult , Electroencephalography , Female , Humans , Male , Serial Learning/physiology , Stroop Test , Young AdultABSTRACT
Beetle luciferases produce different bioluminescence colors from green to red using the same d-luciferin substrate. Despite many studies of the mechanisms and structural determinants of bioluminescence colors with firefly luciferases, the identity of the emitters and the specific active site interactions responsible for bioluminescence color modulation remain elusive. To address these questions, we analyzed the bioluminescence spectra with 6'-amino-D-luciferin (aminoluciferin) and its 5,5-dimethyl analogue using a set of recombinant beetle luciferases that naturally elicit different colors and different pH sensitivities (pH-sensitive, Amydetes vivianii λmax=538 nm, Macrolampis sp2 λmax=564 nm; pH-insensitive, Phrixotrix hirtus λmax=623 nm, Phrixotrix vivianii λmax=546 nm, and Pyrearinus termitilluminans λmax=534 nm), a luciferase-like enzyme (Tenebrionidae, Zophobas morio λmax=613 nm), and mutants of C311 (S314). The green-yellow-emitting luciferases display red-shifted bioluminescence spectra with aminoluciferin in relation to those with D-luciferin, whereas the red-emitting luciferases displayed blue-shifted spectra. Bioluminescence spectra with 5,5-dimethylaminoluciferin, in which enolization is blocked, were almost identical to those of aminoluciferin. Fluorescence probing using 2-(4-toluidino)naphthalene-6-sulfonate and inference with aminoluciferin confirm that the luciferin binding site of the red-shifted luciferases is more polar than in the case of the green-yellow-emitting luciferases. Altogether, the results show that the keto form of excited oxyluciferin is the emitter in beetle bioluminescence and that bioluminescence colors are essentially modulated by interactions of the 6'-hydroxy group of oxyluciferin and basic moieties under the influence of the microenvironment polarity of the active site: a strong interaction between a base moiety and oxyluciferin phenol in a hydrophobic microenvironment promotes green-yellow emission, whereas a more polar environment weakens such interaction promoting red shifts. In pH-sensitive luciferases, a pH-mediated switch from a closed hydrophobic conformation to a more open polar conformation promotes the typical red shift.
Subject(s)
Coleoptera/enzymology , Color , Firefly Luciferin/analogs & derivatives , Firefly Luciferin/metabolism , Luciferases/metabolism , Luminescent Agents/chemistry , Phenols/chemistry , Animals , Binding Sites , Computational Biology , Firefly Luciferin/chemistry , Luciferases/chemistry , Molecular Structure , Protein BindingABSTRACT
Spectroscopic properties of amino-analogs of luciferin and oxyluciferin were investigated to confirm the color modulation mechanism of firefly (beetle) bioluminescence. Fluorescence solvatochromic character of aminooxyluciferin analogs indicates that the bioluminescence of aminoluciferin is useful for evaluating the polarity of a luciferase active site.
