Activity In MT Research Articles

Motion Mechanisms in Macaque MT

The macaque middle temporal area (MT) is exquisitely sensitive to visual motion and there is a large amount of evidence that neural activity in MT is tightly correlated with the perception of motion. The mechanisms by which MT neurons achieve their directional selectivity, however, have received considerably less attention. We investigated the motion-energy model as a description of motion mechanisms in macaque MT. We first confirmed one of the predictions of the motion-energy model; macaques-just like humans-perceive a reversed direction of motion when a stimulus reverses contrast with every displacement (reverse-phi). This reversal of perceived direction had a clear correlate in the neural responses of MT cells, which were predictive of the monkey's behavioral decisions. Second, we investigated how multiple motion-energy components are combined. Psychophysical data have been used to argue that motion-energy components representing opposite directions are subtracted from each other. Our data show, however, that the interactions among motion-energy components are more complex. In particular, we found that the influence of a given component on the response to a stimulus consisting of multiple components depends on factors other than the response to that component alone. This suggests that there are subthreshold nonlinear interactions among multiple motion-energy components; these could take place within MT or in earlier stages of the motion network such as V1. We propose a model that captures the complexity of these component interactions by means of a competitive interaction among the components. This provides a better description of the MT responses than the subtractive motion opponency envisaged in the motion-energy model, even when the latter is combined with a gain-control mechanism. The competitive interaction extends the dynamic range of the cells and allows them to provide information on more subtle changes in motion patterns, including changes that are not purely directional.

Melatonin-mediated regulation of human MT 1 melatonin receptors expressed in mammalian cells

In mammals, the pineal hormone melatonin activates G protein-coupled MT 1 and MT 2 melatonin receptors. Acute exposure of recombinant MT 1 and MT 2 melatonin receptors to supraphysiological concentrations of melatonin differentially regulates these two receptors with the MT 2, but not the MT 1, exhibiting rapid desensitization and internalization. In the present study, we sought to determine whether prolonged exposure to supraphysiological and physiological concentrations of melatonin desensitized and/or internalized the MT 1 melatonin receptor. Using a Chinese hamster ovary (CHO) cell line stably expressing MT 1-FLAG or transiently expressing MT 1-green fluorescent protein (GFP) melatonin receptors, we found that prolonged exposure (8 h) to supraphysiological concentrations of melatonin (100 nM) significantly increased the number of MT 1 melatonin receptors and decreased the affinity ( K i) of melatonin for competition for 2-[ 125 I ]iodomelatonin. A similar treatment also desensitized the MT 1 melatonin receptor-mediated stimulation of [ 35 S ]GTPγS binding, but did not internalize the receptor. In contrast, prolonged exposure to a concentration of melatonin mimicking nocturnal levels (400 pM) did not affect the number of MT 1 melatonin receptors, the affinity for melatonin, or the functional sensitivity of the receptor. We conclude that in vivo endogenous melatonin does not significantly affect the functional sensitivity of MT 1 melatonin receptors, however, exogenous melatonin taken therapeutically at doses above physiological levels could desensitize the receptor thereby affecting physiological responses mediated following activation of MT 1 melatonin receptors.

Human MT+ mediates perceptual filling-in during apparent motion

During apparent motion, spatially distinct items presented in alternation cause the perception of a visual stimulus smoothly traversing the intervening space where no physical stimulus exists. We used fMRI to determine whether the perceptual ‘filling-in’ that underlies this phenomenon has an early or late cortical locus. Subjects viewed a display comprised of concentric rings that elicited apparent motion (two concentric rings presented in alternation), flicker (the same rings presented simultaneously), or real motion. We independently localized the cortical regions corresponding to the path of apparent motion in early visual areas (V1, V2, VP, V3, V4v, V3A), as well as the human motion processing complex (MT+). Cortical activity in the path of apparent motion in early visual areas was similar in amplitude during both apparent motion and flicker. In contrast, cortical activity in MT+ was higher in amplitude during apparent motion than during flicker, but was lower in amplitude than during real motion. In addition, we observed overlap in the cortical loci of MT+ and the lateral occipital complex (LOC), a region involved in shape and object processing. This overlap suggests that these regions could directly interact and thereby support perceived object continuity during apparent motion.

Immortalized cells from the rat suprachiasmatic nucleus express functional melatonin receptors

Immortalized SCN2.2 cells retain most biochemical and biophysical characteristics of the native rat SCN including the expression of clock genes and circadian regulatory proteins, and its distinctive pacemaker function. This study assessed the expression and signaling of MT 1 and MT 2 melatonin receptors in SCN2.2 cells. SCN2.2 cells express MT 1 and MT 2 receptors mRNA as detected by RT-PCR. In situ hybridization with digoxigenin-labeled probes demonstrated that mRNA for MT 1 and MT 2 melatonin receptors is expressed mostly in cells with neuronal-like morphology, representing 10.8±2.2% and 9.8±0.2%, respectively, of the SCN2.2 cell population. MT 1 and MT 2 melatonin receptor proteins are expressed in both rat SCN2.2 cells and rat SCN tissue as demonstrated by Western blot analysis with specific receptor antiserum. Melatonin (0.1–100 nM) inhibited forskolin (20 μM)-stimulated cAMP formation in a dose-dependent manner and this effect was blocked by the competitive melatonin receptor antagonist luzindole (100–1000 nM). Furthermore, melatonin (1 nM) stimulated protein kinase C (PKC) activity by ∼2-fold. The selective MT 2 receptor antagonist 4P-PDOT (100 nM) blocked this effect, indicating that the melatonin-mediated increase in PKC activity occurs through activation of MT 2 melatonin receptors. We conclude that SCN2.2 cells express functional melatonin receptors, providing an in vitro model to unveil the melatonin signaling pathway(s) involved in the regulation of circadian rhythms.

Highly divergent methyltransferases catalyze a conserved reaction in tocopherol and plastoquinone synthesis in cyanobacteria and photosynthetic eukaryotes.

Tocopherols are lipid-soluble compounds synthesized only by photosynthetic eukaryotes and oxygenic cyanobacteria. The pathway and enzymes for tocopherol synthesis are homologous in cyanobacteria and plants except for 2-methyl-6-phytyl-1,4-benzoquinone/2-methyl-6-solanyl-1,4-benzoquinone methyltransferase (MPBQ/MSBQ MT), which catalyzes a key methylation step in both tocopherol and plastoquinone (PQ) synthesis. Using a combined genomic, genetic, and biochemical approach, we isolated and characterized the VTE3 (vitamin E defective) locus, which encodes MPBQ/MSBQ MT in Arabidopsis. The phenotypes of vte3 mutants are consistent with the disruption of MPBQ/MSBQ MT activity to varying extents. The ethyl methanesulfonate-derived vte3-1 allele alters tocopherol composition but has little impact on PQ levels, whereas the null vte3-2 allele is deficient in PQ and alpha- and gamma-tocopherols. In vitro enzyme assays confirmed that VTE3 is the plant functional equivalent of the previously characterized MPBQ/MSBQ MT (Sll0418) from Synechocystis sp PCC6803, although the two proteins are highly divergent in primary sequence. Sll0418 orthologs are present in all fully sequenced cyanobacterial genomes, Chlamydomonas reinhardtii, and the diatom Thalassiosira pseudonana but absent from vascular and nonvascular plant databases. VTE3 orthologs are present in all vascular and nonvascular plant databases and in C. reinhardtii but absent from cyanobacterial genomes. Intriguingly, the only prokaryotic genomes that contain VTE3-like sequences are those of two species of archea, suggesting that, in contrast to all other enzymes of the plant tocopherol pathway, the evolutionary origin of VTE3 may have been archeal rather than cyanobacterial. In vivo analyses of vte3 mutants and the corresponding homozygous Synechocystis sp PCC6803 sll0418::aphII mutant revealed important differences in enzyme redundancy, the regulation of tocopherol synthesis, and the integration of tocopherol and PQ biosynthesis in cyanobacteria and plants.

Interaction of Retinal Image and Eye Velocity in Motion Perception

When we move our eyes, why does the world look stable even as its image flows across our retinas, and why do afterimages, which are stationary on the retinas, appear to move? Current theories say this is because we perceive motion by summation: if an object slips across the retina at r°/s while the eye turns at e°/s, the object's perceived velocity in space should be r + e. We show that activity in MT+, the visual-motion complex in human cortex, does reflect a mix of r and e rather than r alone. But we show also that, for optimal perception, r and e should not summate; rather, the signals coding e interact multiplicatively with the spatial gradient of illumination.

MT(2) melatonin receptors are present and functional in rat caudal artery.

In rat caudal artery, contraction to melatonin results primarily from activation of MT(1) melatonin receptors; however, the role of MT(2) melatonin receptors in vascular responses is controversial. We examined and compared the expression and function of MT(2) receptors with that of MT(1) receptors in male rat caudal artery. MT(1) and MT(2) melatonin receptor mRNA was amplified by reverse transcription-polymerase chain reaction from caudal arteries of three rat strains (i.e., Fisher, Sprague-Dawley, and Wistar). Antisense (but not sense) (33)P-labeled oligonucleotide probes specific for MT(1) or MT(2) receptor mRNA hybridized to smooth muscle, as well as intimal and adventitial layers, of caudal artery. In male Fisher rat caudal artery denuded of endothelium, melatonin was 10 times more potent than 6-chloromelatonin to potentiate contraction to phenylephrine, suggesting activation of smooth muscle MT(1) melatonin receptors. The MT(1)/MT(2) competitive melatonin receptor antagonist luzindole (3 microM), blocked melatonin-mediated contraction (0.1-100 nM) with an affinity constant (K(B) value of 157 nM) similar to that for the human MT(1) receptor. However, at melatonin concentrations above 100 nM, luzindole potentiated the contractile response, suggesting blockade of MT(2) receptors mediating vasorelaxation and/or an inverse agonist effect at MT(1) constitutively active receptors. The involvement of MT(2) receptors in vasorelaxation is supported by the finding that the competitive antagonists 4-phenyl 2-acetamidotetraline and 4-phenyl-2-propionamidotetraline, at MT(2)-selective concentrations (10 nM), significantly enhanced contractile responses to all melatonin concentrations tested (0.1 nM-10 microM). We conclude that MT(2) melatonin receptors expressed in vascular smooth muscle mediate vasodilation in contrast to vascular MT(1) receptors mediating vasoconstriction.

Dynamic Shape Integration in Extrastriate Cortex

Background: In anorthoscopic viewing conditions, observers can perceive a moving object through a narrow slit even when only portions of its contour are visible at any time. We used fMRI to examine the contribution of early and later visual cortical areas to dynamic shape integration. Observers' success at integrating the shape of the slit-viewed object was manipulated by varying the degree to which the stimulus was dynamically distorted. Line drawings of common objects were either moderately distorted, strongly distorted, or shown undistorted. Phenomenologically, increasing the stimulus distortion made both object shape and motion more difficult to perceive.Results: We found that bilateral cortical activity in portions of the ventral occipital cortex, corresponding to known object areas within the lateral occipital complex (LOC), was inversely correlated with the degree of stimulus distortion. We found that activity in left MT+, the human cortical area specialized for motion, showed a similar pattern as the ventral occipital region. The LOC also showed greater activity to a fully visible moving object than to the undistorted slit-viewed object. Area MT+, however, showed more equivalent activity to both the slit-viewed and fully visible moving objects.Conclusions: In early retinotopic cortex, the distorted and undistorted stimuli elicited the same amount of activity. Higher visual areas, however, were correlated with the percept of the coherent object, and this correlation suggests that the shape integration is mediated by later visual cortical areas. Motion information from the dorsal stream may project to the LOC to produce the shape percept.

Neural correlates of structure-from-motion perception in macaque V1 and MT.

Structure-from-motion (SFM) is the perception of three-dimensional shape from motion cues. We used a bistable SFM stimulus, which can be perceived in one of two different ways, to study how neural activity in cortical areas V1 and MT is related to SFM perception. Monkeys performed a depth-order task, where they indicated in which direction the front surface of a rotating SFM cylinder display was moving. To prevent contamination of the neural data because of eye position effects, all experiments with significant effects of radius, vergence, and velocity were excluded. As expected, the activity of approximately 50% of neurons in V1 and approximately 80% of neurons in MT is affected by the stimulus. Furthermore, the activity of 20% of neurons in area V1 is modulated with the percept. This proportion is higher in MT, where the activity of >60% of neurons is modulated with the percept. In both areas, this perceptual modulation occurs only in neurons with activity that is also affected by the stimulus. The perceptual modulation is not correlated with neural tuning properties in area V1, but it is in area MT. Together, these results suggest that V1 is not directly involved in the generation of the SFM percept, whereas MT is. The perceptual modulation in V1 may be attributable to top-down feedback from MT.

Neural Correlates of Structure-from-Motion Perception in Macaque V1 and MT

Structure-from-motion (SFM) is the perception of three-dimensional shape from motion cues. We used a bistable SFM stimulus, which can be perceived in one of two different ways, to study how neural activity in cortical areas V1 and MT is related to SFM perception. Monkeys performed a depth-order task, where they indicated in which direction the front surface of a rotating SFM cylinder display was moving. To prevent contamination of the neural data because of eye position effects, all experiments with significant effects of radius, vergence, and velocity were excluded. As expected, the activity of ∼50% of neurons in V1 and ∼80% of neurons in MT is affected by the stimulus. Furthermore, the activity of 20% of neurons in area V1 is modulated with the percept. This proportion is higher in MT, where the activity of >60% of neurons is modulated with the percept. In both areas, this perceptual modulation occurs only in neurons with activity that is also affected by the stimulus. The perceptual modulation is not correlated with neural tuning properties in area V1, but it is in area MT. Together, these results suggest that V1 is not directly involved in the generation of the SFM percept, whereas MT is. The perceptual modulation in V1 may be attributable to top-down feedback from MT.

An mt(+) gamete-specific nuclease that targets mt(-) chloroplasts during sexual reproduction in C. reinhardtii.

Although the active digestion of mating-type minus (mt-) chloroplast DNA (cpDNA) in young zygotes is considered to be the basis for the uniparental inheritance of cpDNA in Chlamydomonas reinhardtii, little is known about the underlying molecular mechanism. One model of active digestion proposes that nucleases are either synthesized or activated to digest mt- cpDNA. We used a native-PAGE/in gelo assay to investigate nuclease activities in chloroplasts from young zygotes, and identified a novel Ca(2+)-dependent nuclease activity. The timing of activation (approximately 60-90 min after mating) and the localization of the nuclease activity (in mt- chloroplasts) coincided with the active digestion of mt- cpDNA. Furthermore, the activity of the nuclease was coregulated with the maturation of mating-type plus (mt+) gametes, which would enable the efficient digestion of mt- cpDNA. Based on these observations, we propose that the nuclease (designated as Mt(+)-specific DNase, MDN) is a developmentally controlled nuclease that is activated in mt+ gametes and participates in the destruction of mt- cpDNA in young zygotes, thereby ensuring uniparental inheritance of chloroplast traits.

Visual detection of motion speed in humans: spatiotemporal analysis by fMRI and MEG.

Humans take a long time to respond to the slow visual motion of an object. It is not known what neural mechanism causes this delay. We measured magnetoencephalographic neural responses to light spot motion onset within a wide speed range (0.4-500 degrees /sec) and compared these with human reaction times (RTs). The mean response latency was inversely related to the speed of motion up to 100 degrees /sec, whereas the amplitude increased with the speed. The response property at the speed of 500 degrees /sec was different from that at the other speeds. The speed-related latency change was observed when the motion duration was 10 msec or longer in the speed range between 5 and 500 degrees /sec, indicating that the response is directly related to the speed itself. The source of the response was estimated to be around the human MT+ and was validated by functional magnetic imaging study using the same stimuli. The results indicate that the speed of motion is encoded in the neural activity of MT+ and that it can be detected within 10 msec of motion observation. RT to the same motion onset was also inversely related to the speed of motion but the delay could not be explained by the magnetic response latency change. Instead, the reciprocal of RT was linearly related to the reciprocal of the magnetic response latency, suggesting that the visual process interacts with other neural processes for decision and motor preparation.

Auditory and visual attention modulate motion processing in area MT+

Behavioral and physiological studies have established that visual attention to a given feature or location can modulate early visual processing. In the present experiment, we asked whether auditory attention can likewise influence visual processing. We used a visual illusion, the motion aftereffect (MAE), to assess the effects of visual and auditory attention on motion processing in human area MT+. We acquired psychophysical and functional magnetic resonance imaging (fMRI) data while subjects fixated and viewed moving and stationary stimuli in alternating blocks. For each of four motion conditions, we measured the duration of the subsequent MAE, the time for activity in MT+ to return to baseline after motion adaptation (decay time), and the magnitude of MT+ activity during motion adaptation. For each subject, we first obtained measures of motion processing in the absence of attentional demands, by comparing reversing and expanding motion conditions. Subjects perceived the MAE following adaptation to expanding but not reversing motion, as observed previously, and decay times in MT+ were selectively prolonged after expanding motion. We then assessed the effects of performing either a visual or an auditory attentional task during expanding motion adaptation. Performance of the attentional task, whether visual or auditory, produced a significant reduction of subsequent MAE perception and associated decay times in MT+, as compared to expanding motion with fixation only. Both attentional tasks also reduced the magnitude of activation during motion adaptation. These data show that auditory attention, like visual attention, can modify sensory processing at a remarkably early stage of the visual hierarchy.

The plant S-adenosyl-L-methionine:Mg-protoporphyrin IX methyltransferase is located in both envelope and thylakoid chloroplast membranes.

Chlorophyll biosynthesis requires a metabolic dialog between the chloroplast envelope and thylakoids where biosynthetic activities are localized. Here, we report the first plant S-adenosyl-l-methionine:Mg-protoporphyrin IX methyltransferase (MgP(IX)MT) sequence identified in the Arabidopsis genome owing to its similarity with the Synechocystis sp. MgP(IX)MT gene. After expression in Escherichia coli, the recombinant Arabidopsis thaliana cDNA was shown to encode a protein having MgP(IX)MT activity. The full-length polypeptide exhibits a chloroplast transit peptide that is processed during import into the chloroplast. The mature protein contains two functional regions. The C-terminal part aligns with the Synechocystis full-length protein. The corresponding truncated region binds to Ado-met, as assayed by UV crosslinking, and is shown to harbor the MgP(IX)MT activity. Downstream of the cleaved transit peptide, the 40 N-terminal amino acids of the mature protein are very hydrophobic and enhance the association of the protein with the membrane. In A. thaliana and spinach, the MgP(IX)MT protein has a dual localization in chloroplast envelope membranes as well as in thylakoids. The protein is active in each membrane and has the same apparent size corresponding to the processed mature protein. The protein is very likely a monotopic membrane protein embedded within one leaflet of the membrane as indicated by ionic and alkaline extraction of each membrane. The rationale for a dual localization of the protein in the chloroplast is discussed.

Melatonin and N-acetylserotonin inhibit leukocyte rolling and adhesion to rat microcirculation

The hormone melatonin produced by the pineal gland during the daily dark phase regulates a variety of biological processes in mammals. The aim of this study was to determine the effect of melatonin and its precursor N-acetylserotonin on the microcirculation during acute inflammation. Arteriolar diameter, blood flow rate, leukocyte rolling and adhesion were measured in the rat microcirculation in situ by intravital microscopy. Melatonin alone or together with noradrenaline did not affect the arteriolar diameter or blood flow rate. Melatonin inhibited both leukocyte rolling and leukotriene B 4 induced adhesion while its precursor N-acetylserotonin inhibits only leukocyte adhesion. The rank order of potency of agonists and antagonist receptor selective ligands suggested that the activation of MT 2 and MT 3 melatonin binding sites receptors modulate leukocyte rolling and adhesion, respectively. The effect of melatonin and N-acetylserotonin herein described were observed with concentrations in the range of the nocturnal surge, providing the first evidence for a possible physiological role of these hormones in acute inflammation.

Early discrimination of coherent versus incoherent motion by multiunit and synaptic activity in human putative MT+

Early discrimination of coherent versus incoherent motion by multiunit and synaptic activity in human putative MT+

Early discrimination of coherent versus incoherent motion by multiunit and synaptic activity in human putative MT+

A laminar probe was chronically implanted in human putative MT+. The area was specifically responsive to globally coherent visual motion, a crucial aspect of the perception of movement through space. The probe contained 23 microcontacts spaced every 175 microm in a linear array roughly perpendicular to the cortical surface. Current-source density (CSD) and multiunit activity (MUA) were recorded while viewing initially stationary random dot patterns that either moved incoherently or dilated from the central fixation. Onset of visual motion evoked large MUA/CSD activity, with coherent motion evoking earlier and faster-rising MUA/CSD activity than incoherent, in both superficial and deep pyramidal layers. The selective response, peaking at approximately 115 ms, was especially large in deep pyramids, providing evidence that information necessary for visual flow calculations is projected from MT+ at an early latency to distant structures. The early onset of differential MUA/CSD implies that the selectivity of this area does not depend on recurrent inhibition or other intrinsic circuitry to detect coherent motion. The initially greater increase of MUA to coherent stimuli was followed by a greater decrease beginning at approximately 133 ms, apparently because of recurrent inhibition. This resulted in the total MUA being greater to incoherent than coherent stimuli, whereas total rectified CSD was overall greater to coherent than to incoherent stimuli. However, MUA distinguished stationary from moving stimuli more strongly than did CSD. Thus, while estimates of total cell firing (MUA), and of total synaptic activity (CSD) generally correspond to previously reported BOLD results, they may differ in important details.

Activation of MT2 melatonin receptors in rat suprachiasmatic nucleus phase advances the circadian clock

The aim of this study was to identify the melatonin receptor type(s) (MT(1) or MT(2)) mediating circadian clock resetting by melatonin in the mammalian suprachiasmatic nucleus (SCN). Quantitative receptor autoradiography with 2-[(125)I]iodomelatonin and in situ hybridization histochemistry, with either (33)P- or digoxigenin-labeled antisense MT(1) and MT(2) melatonin receptor mRNA oligonucleotide probes, revealed specific expression of both melatonin receptor types in the SCN of inbred Long-Evans rats. The melatonin receptor type mediating phase advances of the circadian rhythm of neuronal firing rate in the SCN slice was assessed using competitive melatonin receptor antagonists, the MT(1)/MT(2) nonselective luzindole and the MT(2)-selective 4-phenyl-2-propionamidotetraline (4P-PDOT). Luzindole and 4P-PDOT (1 nM-1 microM) did not affect circadian phase on their own; however, they blocked both the phase advances (approximately 4 h) in the neuronal firing rate induced by melatonin (3 pM) at temporally distinct times of day [i.e., subjective dusk, circadian time (CT) 10; and dawn, CT 23], as well as the associated increases in protein kinase C activity. We conclude that melatonin mediates phase advances of the SCN circadian clock at both dusk and dawn via activation of MT(2) melatonin receptor signaling.

Visual Responses of Neurons in the Middle Temporal Area of New World Monkeys after Lesions of Striate Cortex

In primates, lesions of striate cortex (V1) result in scotomas in which only rudimentary visual abilities remain. These aspects of vision that survive V1 lesions have been attributed to direct thalamic pathways to extrastriate areas, including the middle temporal area (MT). However, studies in New World monkeys and humans have questioned this interpretation, suggesting that remnants of V1 are responsible for both the activation of MT and residual vision. We studied the visual responses of neurons in area MT in New World marmoset monkeys in the weeks after lesions of V1. The extent of the scotoma in each case was estimated by mapping the receptive fields of cells located near the lesion border and by histological reconstruction. Two response types were observed among the cells located in the part of MT that corresponds, in visuotopic coordinates, to the lesioned part of V1. Many neurons (62%) had receptive fields that were displaced relative to their expected location, so that they represented the visual field immediately surrounding the scotoma. This may be a consequence of a process analogous to the reorganization of the V1 map after retinal lesions. However, another 20% of the cells had receptive fields centered inside the scotoma. Most of these neurons were strongly direction-selective, similar to normal MT cells. These results show that MT cells differ in their responses to lesioning of V1 and that only a subpopulation of MT neurons can be reasonably linked to residual vision and blindsight.

Projection of rods and cones within human visual cortex

There are two basic types of photoreceptors in the retina: rods and cones. Using a single stimulus viewed at two different light levels, we tested whether input from rods and input from cones are topographically segregated at subsequent levels of human visual cortex. Here we show that rod-mediated visual input produces robust activation in area MT+, and in the peripheral representations of multiple retinotopic areas. However, such activation was selectively absent in: (1) a cortical area selectively activated by colored stimuli (V8) and (2) the foveal representations of lower tier retinotopic areas. These cortical differences reflect corresponding differences in perception between scotopic and photopic conditions.