Journal of neurophysiology
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Changes in temperature of up to several degrees have been reported in different brain regions during various behaviors or in response to environmental stimuli. We investigated temperature sensitivity of dopaminergic neurons of the rat substantia nigra pars compacta (SNc), an area important for motor and emotional control, using a combination of electrophysiological techniques, microfluorometry, and RT-PCR in brain slices. Spontaneous neuron firing, cell membrane potential/currents, and intracellular Ca2+ level ([Ca2+]i) were measured during cooling by < or =10 degrees and warming by < or =5 degrees from 34 degrees C. ⋯ Cooling-induced whole cell currents and changes in [Ca2+]i were attenuated by 79% in the presence of 2-aminoethoxydiphenylborane (2-APB; 200 microM), and the outward current was reduced by 20% with ruthenium red (100 microM). RT-PCR conducted with tissue punches containing the SNc revealed mRNA expression for TRPV3 and TRPV4 channels, known to be activated in expression systems by temperature changes within the physiological range. 2-APB, a TRPV3 modulator, increased baseline [Ca2+]i, whereas 4alphaPDD, a TRPV4 agonist, increased spontaneous firing in 7 of 14 neurons tested. We conclude that temperature-gated TRPV3 and TRPV4 cationic channels are expressed in nigral dopaminergic neurons and are constitutively active in brain slices at near physiological temperatures, where they affect the excitability and calcium homeostasis of these neurons.
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Clinical Trial Controlled Clinical Trial
Attenuation of sensory and affective responses to heat pain: evidence for contralateral mechanisms.
Attenuation of responses to repeated sensory events has been thoroughly studied in many modalities; however, attenuation of pain perception has not yet benefitted from such extensive investigation. Described here are two psychophysical studies that examined the effects of repeated exposure to thermal stimuli, assessing potential attenuation of the perception of pain and its possible spatial specificity. Twenty-two subjects were presented thermal stimuli to the volar surface of the right and left forearms. ⋯ Ratings of warmth intensity, pain intensity, and pain unpleasantness were recorded while the subjects performed a thermal sensory discrimination task. Results of study 1 demonstrate that repeated stimulation with noxious heat can lead to long-term attenuation of pain perception; results of study 2 extend these findings of attenuation to both pain intensity and unpleasantness and show that this effect is highly specific to the exposed body side for both aspects of the pain experience. We suggest that the functional plasticity underlying this attenuation effect lies in brain areas with a strong contralateral pattern of pain-related activation.
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Randomized Controlled Trial Clinical Trial
Spatio-temporal separation of roll and pitch balance-correcting commands in humans.
This study was designed to provide evidence for the hypothesis that human balance corrections in response to pitch perturbations are controlled by muscle action mainly about the ankle and knee joints, whereas balance corrections for roll perturbations are controlled predominantly by motion about the hip and lumbro-sacral joints. A dual-axis rotating support surface delivered unexpected random perturbations to the stance of 19 healthy young adults through eight different directions in the pitch and the roll planes and three delays between pitch and roll directions. Roll delays with respect to pitch were no delay, a short 50-ms delay of roll with respect to pitch movements, (chosen to correspond to the onset time of leg muscle stretch reflexes), and a long 150-ms delay between roll and pitch movements (chosen to shift the time when trunk roll velocity peaks to the time when trunk peak pitch velocity normally occurs). ⋯ Lower leg and trunk muscle activity appears to have a dual action in balance corrections. In trunk muscles the main action is to correct for roll perturbations and the lesser action may be an anticipatory stabilizing reaction for pitch perturbations. Likewise, the small changes in lower leg muscle activity may result from a generalized stabilizing reaction to roll perturbations, but the main action is to correct for pitch perturbations.
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Three sources of interlimb interactions have been postulated to underlie the stability characteristics of bimanual coordination but have never been evaluated in conjunction: integrated timing of feedforward control signals, phase entrainment by contralateral afference, and timing corrections based on the perceived error of relative phase. In this study, the relative contributions of these interactions were discerned through systematic comparisons of five tasks involving rhythmic flexion-extension movements about the wrist, performed bimanually (in-phase and antiphase coordination) or unimanually with or without comparable passive movements of the contralateral hand. The main findings were the following. 1) Contralateral passive movements during unimanual active movements induced phase entrainment to interlimb phasing of either 0 degrees (in-phase) or 180 degrees (antiphase). 2) Entrainment strength increased with the passive movements' amplitude, but was similar for in-phase and antiphase movements. 3) Coordination of unimanual active movements with passive movements of the contralateral hand (kinesthetic tracking) was characterized by similar bilateral EMG activity as observed in active bimanual coordination. 4) During kinesthetic tracking the timing of the movements of the active hand was modulated by afference-based error corrections, which were more pronounced during in-phase coordination. 5) Indications of in-phase coordination being more stable than antiphase coordination were most prominent during active bimanual coordination and marginal during kinesthetic tracking. Together the results indicated that phase entrainment by contralateral afference contributed equally to the stability of in-phase and antiphase coordination, and that differential stability of these patterns depended predominantly on integrated timing of feedforward signals, with only a minor role for afference-based error corrections.
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Extended suprathreshold vibratory stimulation applied to the skin results in a desensitization of cutaneous mechanoreceptive afferents. In a companion paper, we describe the dependence of the threshold shift on the parameters of the adapting stimulus and discuss neural mechanisms underlying afferent adaptation. Here we describe the time-course of afferent adaptation and recovery. ⋯ We also showed that threshold adaptation is accompanied by a shift in the timing of the spikes within individual cycles of the adapting stimulus (i.e., a shift in the impulse phase). We invoked an integrate-and-fire model to explore possible mechanisms underlying afferent adaptation. Finally, we found that the time-course of afferent adaptation is more rapid than that of its psychophysical counterpart, as is the time-course of recovery from adaptation, suggesting that central factors play a role in the psychophysical phenomenon.