A profound understanding of protein structure and mechanism requires dedicated experimental and theoretical tools to elucidate electrostatic and hydrogen bonding interactions in proteins. In this work, we employed an approach to disentangle noncovalent and hydrogen-bonding electric field changes during the reaction cascade of a multidomain protein, i.e.
View Article and Find Full Text PDFThe recently discovered Neorhodopsin (NeoR) exhibits absorption and emission maxima in the near-infrared spectral region, which together with the high fluorescence quantum yield makes it an attractive retinal protein for optogenetic applications. The unique optical properties can be rationalized by a theoretical model that predicts a high charge transfer character in the electronic ground state (S) which is otherwise typical of the excited state S in canonical retinal proteins. The present study sets out to assess the electronic structure of the NeoR chromophore by resonance Raman (RR) spectroscopy since frequencies and relative intensities of RR bands are controlled by the ground and excited state's properties.
View Article and Find Full Text PDFDissecting the intricate networks of covalent and non-covalent interactions that stabilize complex protein structures is notoriously difficult and requires subtle atomic-level exchanges to precisely affect local chemical functionality. The function of the Orange Carotenoid Protein (OCP), a light-driven photoswitch involved in cyanobacterial photoprotection, depends strongly on two H-bonds between the 4-ketolated xanthophyll cofactor and two highly conserved residues in the C-terminal domain (Trp288 and Tyr201). By orthogonal translation, we replaced Trp288 in OCP with 3-benzothienyl--alanine (BTA), thereby exchanging the imino nitrogen for a sulphur atom.
View Article and Find Full Text PDFPhytochromes, found in plants, fungi, and bacteria, exploit light as a source of information to control physiological processes photoswitching between two states of different physiological activity, a red-absorbing Pr and a far-red-absorbing Pfr state. Depending on the relative stability in the dark, bacterial phytochromes are divided into prototypical and bathy phytochromes, where the stable state is Pr and Pfr, respectively. In this work we studied representatives of these groups (prototypical Agp1 and bathy Agp2 from ) together with the bathy-like phytochrome BphP from by resonance Raman and IR difference spectroscopy.
View Article and Find Full Text PDFObjective: In some cases of incomplete cervical spinal cord injury (iSCI) there is marked paresis and dysfunction of upper-extremity movement but not lower-extremity movement. A continued explanation of such symptoms is a somatotopic organization of corticospinal tract (CST) fibers passing through the decussation at the craniovertebral junction (CVJ) and lateral CST (LCST). In central cord syndrome, it has been suggested that injury to the core of the cervical cord may include selective damage to medially located arm/hand LCST fibers, without compromising laterally located leg fibers.
View Article and Find Full Text PDFBacterial phytochromes are sensoric photoreceptors that transform light absorbed by the photosensor core module (PCM) to protein structural changes that eventually lead to the activation of the enzymatic output module. The underlying photoinduced reaction cascade in the PCM starts with the isomerization of the tetrapyrrole chromophore, followed by conformational relaxations, proton transfer steps, and a secondary structure transition of a peptide segment (tongue) that is essential for communicating the signal to the output module. In this work, we employed various static and time-resolved IR and resonance Raman spectroscopic techniques to study the structural and reaction dynamics of the Meta-F intermediate of both the PCM and the full-length (PCM and output module) variant of the bathy phytochrome Agp2 from Agrobacterium fabrum.
View Article and Find Full Text PDFPhytochromes switch between a physiologically inactive and active state via a light-induced reaction cascade, which is initiated by isomerization of the tetrapyrrole chromophore and leads to the functionally relevant secondary structure transition of a protein segment (tongue). Although details of the underlying cause-effect relationships are not known, electrostatic fields are likely to play a crucial role in coupling chromophores and protein structural changes. Here, we studied local electric field changes during the photoconversion of the dark state Pfr to the photoactivated state Pr of the bathy phytochrome Agp2.
View Article and Find Full Text PDFMany investigators who make extracellular recordings from populations of cortical neurons are now using spike shape parameters, and particularly spike duration, as a means of classifying different neuronal sub-types. Because of the nature of the experimental approach, particularly that involving nonhuman primates, it is very difficult to validate directly which spike characteristics belong to particular types of pyramidal neurons and interneurons, as defined by modern histological approaches. This commentary looks at the way antidromic identification of pyramidal cells projecting to different targets, and in particular, pyramidal tract neurons (PTN), can inform the utility of spike width classification.
View Article and Find Full Text PDFObjective: A recent neuroanatomical staging scheme of amyotrophic lateral sclerosis (ALS) indicates that a cortical lesion may spread, as a network disorder, both at the cortical level and via corticofugal tracts, including corticospinal projections providing direct monosynaptic input to α-motoneurons. These projections are involved preferentially and early in ALS. If these findings are clinically relevant, the pattern of paresis in ALS should primarily involve those muscle groups that receive the strongest direct corticomotoneuronal (CM) innervation.
View Article and Find Full Text PDFPyramidal tract neurons (PTNs) within macaque rostral ventral premotor cortex (F5) and (M1) provide direct input to spinal circuitry and are critical for skilled movement control. Contrary to initial hypotheses, they can also be active during action observation, in the absence of any movement. A population-level understanding of this phenomenon is currently lacking.
View Article and Find Full Text PDFPlant phytochromes are red/far-red photochromic photoreceptors that act as master regulators of development, controlling the expression of thousands of genes. Here, we describe the crystal structures of four plant phytochrome sensory modules, three at about 2 Å resolution or better, including the first of an A-type phytochrome. Together with extensive spectral data, these structures provide detailed insight into the structure and function of plant phytochromes.
View Article and Find Full Text PDFWe review the current knowledge about the part that motor cortex plays in the preparation and generation of movement, and we discuss the idea that corticospinal neurons, and particularly those with cortico-motoneuronal connections, act as 'command' neurons for skilled reach-to-grasp movements in the primate. We also review the increasing evidence that it is active during processes such as action observation and motor imagery. This leads to a discussion about how movement is inhibited and stopped, and the role in these for disfacilitation of the corticospinal output.
View Article and Find Full Text PDFWe found that laser irradiation, being widely used in perovskite photovoltaics for both laser scribing and materials characterization, inevitably causes a cascade of complex photo- and thermochemical conjugated reactions, material melting, and ablation with deep morphological and composition changes of perovskite thin films over a much larger area compared to the initial laser spot. A crucial issue in the advancing or suppression of these degradation processes is related to the origin of the surrounding atmosphere. In particular, an effective approach utilizing an inert gas flow directed onto the exposed area is suggested for the first time to eliminate the negative consequences of perovskite laser scribing.
View Article and Find Full Text PDFPhytochromes are biological photoswitches that interconvert between two parent states (Pr and Pfr). The transformation is initiated by photoisomerization of the tetrapyrrole chromophore, followed by a sequence of chromophore and protein structural changes. In the last step, a phytochrome-specific peptide segment (tongue) undergoes a secondary structure change, which in prokaryotic phytochromes is associated with the (de)activation of the output module.
View Article and Find Full Text PDFAnatomical studies report a large proportion of fine myelinated fibers in the primate pyramidal tract (PT), while very few PT neurons (PTNs) with slow conduction velocities (CV) (<~10 m/s) are reported electrophysiologically. This discrepancy might reflect recording bias toward fast PTNs or prevention of antidromic invasion by recurrent inhibition (RI) of slow PTNs from faster axons. We investigated these factors in recordings made with a polyprobe (32 closely-spaced contacts) from motor cortex of anesthetized rats (n = 2) and macaques (n = 3), concentrating our search on PTNs with long antidromic latencies (ADLs).
View Article and Find Full Text PDFConnectivity-based parcellation of subcortical structures using diffusion tractography is now a common paradigm in neuroscience. These analyses often imply voxel-level specificity of connectivity, and the formation of compact, spatially coherent clusters is often taken as strong imaging-based evidence for anatomically distinct subnuclei in an individual. In this study, we demonstrate that internal structure in diffusion anisotropy is not necessary for a plausible parcellation to be obtained, by spatially permuting diffusion parameters within the thalami and repeating the parcellation.
View Article and Find Full Text PDFThis feature article focuses on the discrepancy between the distribution of axon diameters within the primate corticospinal tract, determined neuroanatomically, and the distribution of axonal conduction velocities within the same tract, determined electrophysiologically. We point out the importance of resolving this discrepancy for a complete understanding of corticospinal functions, and discuss the various explanations for the mismatch between anatomy and physiology.
View Article and Find Full Text PDFThere are substantial differences across species in the organization and function of the motor pathways. These differences extend to basic electrophysiological properties. Thus, in rat motor cortex, pyramidal cells have long duration action potentials, while in the macaque, some pyramidal neurons exhibit short duration "thin" spikes.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2017
Imaging, electrophysiological, and lesion studies have shown a relationship between the parahippocampal cortex (PHC) and the processing of spatial scenes. Our present knowledge of PHC, however, is restricted to the macroscopic properties and dynamics of bulk tissue; the behavior and selectivity of single parahippocampal neurons remains largely unknown. In this study, we analyzed responses from 630 parahippocampal neurons in 24 neurosurgical patients during visual stimulus presentation.
View Article and Find Full Text PDFThe activity of mirror neurons in macaque ventral premotor cortex (PMv) and primary motor cortex (M1) is modulated by the observation of another's movements. This modulation could underpin well documented changes in EEG/MEG activity indicating the existence of a mirror neuron system in humans. Because the local field potential (LFP) represents an important link between macaque single neuron and human noninvasive studies, we focused on mirror properties of intracortical LFPs recorded in the PMv and M1 hand regions in two macaques while they reached, grasped and held different objects, or observed the same actions performed by an experimenter.
View Article and Find Full Text PDFWe used a face adaptation paradigm to bias the perception of ambiguous images of faces and study how single neurons in the human medial temporal lobe (MTL) respond to the same images eliciting different percepts. The ambiguous images were morphs between the faces of two familiar individuals, chosen because at least one MTL neuron responded selectively to one but not to the other face. We found that the firing of MTL neurons closely followed the subjects' perceptual decisions--i.
View Article and Find Full Text PDFJ Neurophysiol
September 2014
Small axons far outnumber larger fibers in the corticospinal tract, but the function of these small axons remains poorly understood. This is because they are difficult to identify, and therefore their physiology remains obscure. To assess the extent of the mismatch between anatomic and physiological measures, we compared conduction time and velocity in a large number of macaque corticospinal neurons with the distribution of axon diameters at the level of the medullary pyramid, using both light and electron microscopy.
View Article and Find Full Text PDFHere, we report the properties of neurons with mirror-like characteristics that were identified as pyramidal tract neurons (PTNs) and recorded in the ventral premotor cortex (area F5) and primary motor cortex (M1) of three macaque monkeys. We analysed the neurons' discharge while the monkeys performed active grasp of either food or an object, and also while they observed an experimenter carrying out a similar range of grasps. A considerable proportion of tested PTNs showed clear mirror-like properties (52% F5 and 58% M1).
View Article and Find Full Text PDFMirror neurons were first discovered in area F5 of macaque monkeys. In humans, noninvasive studies have demonstrated an increased blood oxygen level-dependent (BOLD) signal in homologous motor areas during action observation. One approach to demonstrating that this indicates the existence of mirror neurons in humans has been to employ functional (f)MRI adaptation to test whether the same population of neurons is active during both observation and execution conditions.
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