Cranial kinesis in geckoes: functional implications.
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Although it is generally assumed that cranial kinesis is a plesiomorphic characteristic in squamates, experimental data tend to contradict this hypothesis. In particular, coupled kinesis (i.e. streptostyly and mesokinesis) presumably arose independently in only a limited number of highly specialised groups. In this study, we investigated cranial kinesis in one of the most specialised of these groups: geckoes. On the basis of cineradiographic and electromyographic data, the fast opening and the slow closing/power stroke phases were modelled to elucidate possible functions of the observed kinesis. The results of these analyses show that the retraction of the muzzle unit during crushing is a self-reinforcing system that increases bite force and reduces the joint forces; the active protraction of the kinetic system during jaw opening, in contrast, enhances opening speed through the coupling of the intracranial units. It can be argued that cranial kinesis in geckoes is probably not an adaptive trait as such but, instead, a consequence of the 'Bauplan' of the cranial system in these animals. Presumably as a result of constructional constraints on the size of the jaw musculature and eyes, the supratemporal and postorbital bars were lost, which resulted in enormous mobility in the skull. To counteract the potential negative factors associated with this (decrease in bite force, skull damage), the kinetic system may have become coupled, and thus functional. (+info)
Temporary inactivation in the primate motor thalamus during visually triggered and internally generated limb movements.
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To better understand the contribution of cerebellar- and basal ganglia-receiving areas of the thalamus [ventral posterolateral nucleus, pars oralis (VPLo), area X, ventral lateral nucleus, pars oralis (VLo), or ventral anterior nucleus, pars parvicellularis (VApc)] to movements based on external versus internal cues, we temporarily inactivated these individual nuclei in two monkeys trained to make visually triggered (VT) and internally generated (IG) limb movements. Infusions of lignocaine centered within VPLo caused hemiplegia during which movements of the contralateral arm rarely were performed in either task for a short period of time ( approximately 5-30 min). When VT responses were produced, they had prolonged reaction times and movement times and a higher incidence of trajectory abnormalities compared with responses produced during the preinfusion baseline period. In contrast, those IG responses that were produced remained relatively normal. Infusions centered within area X never caused hemiplegia. The only deficits observed were an increase in reaction time and movement amplitude variability and a higher incidence of trajectory abnormalities during VT trials. Every other aspect of both the VT and IG movements remained unchanged. Infusions centered within VLo reduced the number of movements attempted during each block of trials. This did not appear to be due to hemiplegia, however, as voluntary movements easily could be elicited outside of the trained tasks. The other main deficit resulting from inactivation of VLo was an increased reaction time in the VT task. Finally, infusions centered within VApc caused IG movements to become slower and smaller in amplitude, whereas VT movements remained unchanged. Control infusions with saline did not cause any consistent deficits. This pattern of results implies that VPLo and VLo play a role in the production of movements in general regardless of the context under which they are performed. They also suggest that VPLo contributes more specifically to the execution of movements that are visually triggered and guided, whereas area X contributes specifically to the initiation of such movements. In contrast, VApc appears to play a role in the execution of movements based on internal cues. These results are consistent with the hypothesis that specific subcircuits within the cerebello- and basal ganglio-thalamo-cortical systems preferentially contribute to movements based on external versus internal cues. (+info)
Growth/differentiation factor-15/macrophage inhibitory cytokine-1 is a novel trophic factor for midbrain dopaminergic neurons in vivo.
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Transforming growth factor-betas (TGF-betas) constitute an expanding family of multifunctional cytokines with prominent roles in development, cell proliferation, differentiation, and repair. We have cloned, expressed, and raised antibodies against a distant member of the TGF-betas, growth/differentiation factor-15 (GDF-15). GDF-15 is identical to macrophage inhibitory cytokine-1 (MIC-1). GDF-15/MIC-1 mRNA and protein are widely distributed in the developing and adult CNS and peripheral nervous systems, including choroid plexus and CSF. GDF-15/MIC-1 is a potent survival promoting and protective factor for cultured and iron-intoxicated dopaminergic (DAergic) neurons cultured from the embryonic rat midbrain floor. The trophic effect of GDF-15/MIC-1 was not accompanied by an increase in cell proliferation and astroglial maturation, suggesting that GDF-15/MIC-1 probably acts directly on neurons. GDF-15/MIC-1 also protects 6-hydroxydopamine (6-OHDA)-lesioned nigrostriatal DAergic neurons in vivo. Unilateral injections of GDF-15/MIC-1 into the medial forebrain bundle just above the substantia nigra (SN) and into the left ventricle (20 microgram each) immediately before a 6-OHDA injection (8 microgram) prevented 6-OHDA-induced rotational behavior and significantly reduced losses of DAergic neurons in the SN. This protection was evident for at least 1 month. Administration of 5 microgram of GDF-15/MIC-1 in the same paradigm also provided significant neuroprotection. GDF-15/MIC-1 also promoted the serotonergic phenotype of cultured raphe neurons but did not support survival of rat motoneurons. Thus, GDF-15/MIC-1 is a novel neurotrophic factor with prominent effects on DAergic and serotonergic neurons. GDF-15/MIC-1 may therefore have a potential for the treatment of Parkinson's disease and disorders of the serotonergic system. (+info)
Visual and tactile information about object-curvature control fingertip forces and grasp kinematics in human dexterous manipulation.
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Most objects that we manipulate have curved surfaces. We have analyzed how subjects during a prototypical manipulatory task use visual and tactile sensory information for adapting fingertip actions to changes in object curvature. Subjects grasped an elongated object at one end using a precision grip and lifted it while instructed to keep it level. The principal load of the grasp was tangential torque due to the location of the center of mass of the object in relation to the horizontal grip axis joining the centers of the opposing grasp surfaces. The curvature strongly influenced the grip forces required to prevent rotational slips. Likewise the curvature influenced the rotational yield of the grasp that developed under the tangential torque load due to the viscoelastic properties of the fingertip pulps. Subjects scaled the grip forces parametrically with object curvature for grasp stability. Moreover in a curvature-dependent manner, subjects twisted the grasp around the grip axis by a radial flexion of the wrist to keep the desired object orientation despite the rotational yield. To adapt these fingertip actions to object curvature, subjects could use both vision and tactile sensibility integrated with predictive control. During combined blindfolding and digital anesthesia, however, the motor output failed to predict the consequences of the prevailing curvature. Subjects used vision to identify the curvature for efficient feedforward retrieval of grip force requirements before executing the motor commands. Digital anesthesia caused little impairment of grip force control when subjects had vision available, but the adaptation of the twist became delayed. Visual cues about the form of the grasp surface obtained before contact was used to scale the grip force, whereas the scaling of the twist depended on visual cues related to object movement. Thus subjects apparently relied on different visuomotor mechanisms for adaptation of grip force and grasp kinematics. In contrast, blindfolded subjects used tactile cues about the prevailing curvature obtained after contact with the object for feedforward adaptation of both grip force and twist. We conclude that humans use both vision and tactile sensibility for feedforward parametric adaptation of grip forces and grasp kinematics to object curvature. Normal control of the twist action, however, requires digital afferent input, and different visuomotor mechanisms support the control of the grasp twist and the grip force. This differential use of vision may have a bearing to the two-stream model of human visual processing. (+info)
NXY-059, a free radical--trapping agent, substantially lessens the functional disability resulting from cerebral ischemia in a primate species.
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BACKGROUND AND PURPOSE: NXY-059 is a novel nitrone with free radical-trapping properties that has a considerable neuroprotective effect in rats. We have now examined the efficacy of this drug at reducing long-term functional disability in a primate model of stroke. METHODS: Twelve monkeys were trained and tested on a variety of behavioral tasks used to dissociate and quantify motor and spatial deficits. Five minutes after permanent occlusion of the right middle cerebral artery, monkeys received a 1-mL intravenous infusion of either saline or NXY-059 (28 mg x kg(-1)), and osmotic minipumps, model 2001D, were implanted subcutaneously to provide continuous drug or saline infusion for 48 hours. Drug-filled pumps released NXY-059 at 16 mg x kg(-1) x h(-1). The monkeys were retested 3 and 10 weeks after surgery to assess functional disability. Surgery, behavioral testing, and histology were all done blinded to treatment condition. RESULTS: NXY-059-treated monkeys were significantly better at reaching with their hemiparetic arm than were saline-treated monkeys when retested 3 weeks (P:<0.01) and 10 weeks (P:<0.01) after surgery. Drug treatment also significantly lessened the degree of spatial perceptual neglect (P:<0.01), a debilitating though ameliorating consequence of this infarct. NXY-059 treatment reduced the overall amount of brain damage by >50% of saline-treatment values, with similar levels of protection afforded to both white and gray matter. CONCLUSIONS: This novel drug has a substantial protective effect, lessening the disability caused by an experimentally induced stroke in a primate species. These findings provide considerable encouragement for the clinical development of NXY-059. (+info)
Neural correlates for angular head velocity in the rat dorsal tegmental nucleus.
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Many neurons in the rat lateral mammillary nuclei (LMN) fire selectively in relation to the animal's head direction (HD) in the horizontal plane independent of the rat's location or behavior. One hypothesis of how this representation is generated and updated is via subcortical projections from the dorsal tegmental nucleus (DTN). Here we report the type of activity in DTN neurons. The majority of cells (75%) fired as a function of the rat's angular head velocity (AHV). Cells exhibited one of two types of firing patterns: (1) symmetric, in which the firing rate was positively correlated with AHV during head turns in both directions, and (2) asymmetric, in which the firing rate was positively correlated with head turns in one direction and correlated either negatively or not at all in the opposite direction. In addition to modulation by AHV, some of the AHV cells (40.1%) were weakly modulated by the rat's linear velocity, and a smaller number were modulated by HD (11%) or head pitch (15.9%). Autocorrelation analyses indicated that with the head stationary, AHV cells displayed irregular discharge patterns. Because afferents from the DTN are the major source of information projecting to the LMN, these results suggest that AHV information from the DTN plays a significant role in generating the HD signal in LMN. A model is proposed showing how DTN AHV cells can generate and update the LMN HD cell signal. (+info)
Modification of social memory, hypothalamic-pituitary-adrenal axis, and brain asymmetry by neonatal novelty exposure.
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Although corticosterone (a stress hormone) is known to influence social behavior and memory processes, little has been explored concerning its modulatory role in social recognition. In rats, social recognition memory for conspecifics typically lasts <2 hr when evaluated using a habituation paradigm. Using neonatal novelty exposure, a brief and transient early life stimulation method known to produce long-lasting changes in the hypothalamic-pituitary-adrenal axis, we found that social recognition memory was prolonged to at least 24 hr during adulthood. This prolonged social memory was paralleled by a reduction in the basal blood concentration of corticosterone. The same neonatal stimulation also resulted in a functional asymmetry expressed as a greater right-turn preference in a novel environment. Rats that preferred to turn right showed better social recognition memory. These inter-related changes in basal blood corticosterone concentration, turning asymmetry, and social recognition memory suggest that stress hormones and brain asymmetry are likely candidates for modulating social memory. Furthermore, given that neonatal stimulation has been shown to improve learning and memory performance primarily under aversive learning situations, the neonatal novelty exposure-induced enhancement in social recognition broadens the impact of early life stimulation to include the social domain. (+info)
Polarized increase of calcium and nucleokinesis in tangentially migrating neurons.
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Cortical interneurons originate from the ganglionic eminences and reach their final position in the cortex via tangential migratory routes. The mechanisms of this migration are poorly understood. Here we have performed confocal time-lapse analysis of cell movement in the intermediate zone of embryonic mouse cortical slices in order to directly visualize their mode of migration. Tangentially migrating neurons moved by nucleokinesis, characterized by active phases of discontinuous advances of the nucleus followed by periods of quiescence. Dissociated cells from the ganglionic eminences also showed nucleokinesis associated with an increase of intracellular calcium, [Ca(2+)](i) Calcium elevation was greatest in the proximal region of the leading process, a zone with a wide distribution of gamma-tubulin. General increases in [Ca(2+)](i) elicited by microperfussion with neurotransmitters did not elicit nucleokinesis. These results show that tangential migration uses nucleokinesis, a cell-intrinsic process in which calcium signalling is local, directional and highly regulated. (+info)