Journal of neurophysiology
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Randomized Controlled Trial
Dyspnea as a noxious sensation: inspiratory threshold loading may trigger diffuse noxious inhibitory controls in humans.
Dyspnea, a leading respiratory symptom, shares many clinical, physiological, and psychological features with pain. Both activate similar brain areas. The neural mechanisms of dyspnea are less well described than those of pain. ⋯ The myotatic H-reflex was not inhibited by inspiratory loading, arguing against postsynaptic alpha motoneuron inhibition. Dyspnea, like pain, thus induced counterirritation, possibly indicating a C-fiber stimulation and activation of diffuse noxious inhibitory descending controls known to project onto spinal dorsal horn wide dynamic range neurons. This confirms the noxious nature of certain types of breathlessness, thus opening new physiological and perhaps therapeutic perspectives.
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Clinical Trial
Reward value coding distinct from risk attitude-related uncertainty coding in human reward systems.
When deciding between different options, individuals are guided by the expected (mean) value of the different outcomes and by the associated degrees of uncertainty. We used functional magnetic resonance imaging to identify brain activations coding the key decision parameters of expected value (magnitude and probability) separately from uncertainty (statistical variance) of monetary rewards. Participants discriminated behaviorally between stimuli associated with different expected values and uncertainty. ⋯ Uncertainty-related activations covaried with individual risk aversion in lateral orbitofrontal regions and risk-seeking in more medial areas. Furthermore, activations in expected value-coding regions in prefrontal cortex covaried differentially with uncertainty depending on risk attitudes of individual participants, suggesting that separate prefrontal regions are involved in risk aversion and seeking. These data demonstrate the distinct coding in key reward structures of the two basic and crucial decision parameters, expected value, and uncertainty.
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Communication is one of the fundamental components of both human and nonhuman animal behavior. Auditory communication signals (i.e., vocalizations) are especially important in the socioecology of several species of nonhuman primates such as rhesus monkeys. In rhesus, the ventrolateral prefrontal cortex (vPFC) is thought to be part of a circuit involved in representing vocalizations and other auditory objects. ⋯ In a first neural study, however, we found that the tuning properties of vPFC neurons did not emphasize these particularly informative spectrotemporal features. In a second neural study, we found that a first-order linear model (the spectrotemporal receptive field) is not a good predictor of vPFC activity. The results of these two neural studies are consistent with the hypothesis that the vPFC is not involved in coding the first-order acoustic properties of a stimulus but is involved in processing the higher-order information needed to form representations of auditory objects.
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The recent discoveries of cold-sensitive transient receptor potential (TRP) channels prompted us to investigate the responses of neurons in trigeminal subnucleus caudalis (Vc) to intraoral cooling and agonists of TRPM8 and TRPA1. Single units responsive to lingual cooling were recorded in superficial laminae of Vc in thiopental-anesthetized rats. All units responded to noxious heat and 88% responded to menthol. ⋯ Most menthol-responsive units also responded to the TRPA1 agonists cinnamaldehyde and mustard oil, and the TRPV1 agonist capsaicin. Units in superficial Vc receive convergent input from primary afferents that express TRPM8, TRPA1, and/or TRPV1 channels, either directly or indirectly via intersubnuclear pathways. The convergent nature of these units suggests a general role in signaling noxious stimuli.
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The most common single-nucleotide polymorphism (SNP) of the human mu-opioid receptor (hMOR) gene occurs at position 118 (A118G) and results in substitution of asparagine to aspartate at the N-terminus. The purpose of the present study was to compare the pharmacological profile of several opioid agonists to heterologously expressed hMOR and N-type Ca(2+) channels in sympathetic neurons. cDNA constructs coding for wild-type and mutant hMOR were microinjected in rat superior cervical ganglion neurons and N-type Ca(2+) channel modulation was investigated using the whole cell variant of the patch-clamp technique. Concentration-response relationships were generated with the following selective MOR agonists: DAMGO, morphine, morphine-6-glucuronide (M-6-G), and endomorphin I. ⋯ On the other hand, the rank order in mutant-expressing neurons was: DAMGO (14) >> morphine (39) >> endomorphin I (74) congruent with M-6-G (82), with a twofold leftward shift for both DAMGO and morphine. The DAMGO-mediated Ca(2+) current inhibition was abolished by the selective MOR blocker, CTAP, and by pertussis toxin pretreatment of neurons expressing either hMOR subtype. These results suggest that the A118G variant MOR exhibits an altered signal transduction pathway and may help explain the variability of responses to opiates observed with carriers of the mutant allele.