Accumulating evidence underscores the importance of ligand-receptor dynamics in shaping cellular signaling. In the nervous system, growth factor-activated Trk receptor trafficking serves to convey biochemical signaling that underlies fundamental neural functions. Focus has been placed on axonal trafficking but little is known about growth factor-activated Trk dynamics in the neuronal soma, particularly at the molecular scale, due in large part to technical hurdles in observing individual growth factor-Trk complexes for long periods of time inside live cells. Quantum dots (QDs) are intensely fluorescent nanoparticles that have been used to study the dynamics of ligand-receptor complexes at the plasma membrane but the value of QDs for investigating ligand-receptor intracellular dynamics has not been well exploited. The current study establishes that QD conjugated brain-derived neurotrophic factor (QD-BDNF) binds to TrkB receptors with high specificity, activates TrkB downstream signaling, and allows single QD tracking capability for long recording durations deep within the soma of live neurons. QD-BDNF complexes undergo internalization, recycling, and intracellular trafficking in the neuronal soma. These trafficking events exhibit little time-synchrony and diverse heterogeneity in underlying dynamics that include phases of sustained rapid motor transport without pause as well as immobility of surprisingly long-lasting duration (several minutes). Moreover, the trajectories formed by dynamic individual BDNF complexes show no apparent end destination; BDNF complexes can be found meandering over long distances of several microns throughout the expanse of the neuronal soma in a circuitous fashion. The complex, heterogeneous nature of neuronal soma trafficking dynamics contrasts the reported linear nature of axonal transport data and calls for models that surpass our generally limited notions of nuclear-directed transport in the soma. QD-ligand probes are poised to provide understanding of how the molecular mechanisms underlying intracellular ligand-receptor trafficking shape cell signaling under conditions of both healthy and dysfunctional neurological disease models.
Research during the past two decades has demonstrated an important role of the vestibular system in topographical orientation and memory and the network of neural structures associated with them. Almost all of the supporting data have come from animal or human clinical studies, however. The purpose of the present study was to investigate the link between vestibular function and topographical memory in normal elderly humans. Twenty-five participants aged 70 to 85 years who scored from mildly impaired to normal on the Montreal Cognitive Assessment (MoCA) received three topographical memory tests: the Camden Topographical Recognition Memory Test (CTMRT), a computerized topographical mental rotation test (TMRT), and a virtual pond maze (VPM). They also received six vestibular or oculomotor tests: optokinetic nystagmus (OKN), visual pursuit (VP), actively generated vestibulo-ocular reflex (VOR), the sensory orientation test (SOT) for posture, and two measures of rotational memory (error in degrees, or RM°, and correct directional recognition, or RM?). The only significant bivariate correlations were among the three vestibular measures primarily assessing horizontal canal function (VOR, RM°, and RM?). A multiple regression analysis showed significant relationships between vestibular and demographic predictors and both the TMRT (R = 0.78) and VPM (R = 0.66) measures. The significant relationship between the vestibular and topographical memory measures supports the theory that vestibular loss may contribute to topographical memory impairment in the elderly.
An eyewear mounted visual display ("User-worn see-through display") projecting an artificial horizon aligned with the users head and body position in space can prevent or lessen motion sickness in susceptible individuals when in a motion provocative environment as well as aid patients undergoing vestibular rehabilitation. In this project, a wearable display device, including software technology and hardware, was developed and a phase I feasibility study and phase II clinical trial for safety and efficacy were performed.
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