Neuron
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Comparative Study
Coding of reward risk by orbitofrontal neurons is mostly distinct from coding of reward value.
Risky decision-making is altered in humans and animals with damage to the orbitofrontal cortex. However, the cellular function of the intact orbitofrontal cortex in processing information relevant for risky decisions is unknown. We recorded responses of single orbitofrontal neurons while monkeys viewed visual cues representing the key decision parameters, reward risk and value. ⋯ A population of orbitofrontal neurons showed a distinctive risk signal: their cues and reward responses covaried monotonically with the variance of the different reward distributions without monotonically coding reward value. Furthermore, a small but statistically significant fraction of risk responses also coded reward value. These risk signals may provide physiological correlates for the role of the orbitofrontal cortex in risk processing.
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The natural response to itch sensation is to scratch, which relieves the itch through an unknown mechanism. Interaction between pain and itch has been frequently demonstrated, and the selectivity hypothesis of itch, based on data from electrophysiological and behavioral experiments, postulates the existence of primary pain afferents capable of repressing itch. ⋯ The increased itch behavior was reduced by administration of antihistaminergic drugs and by genetic deletion of the gastrin-releasing peptide receptor, demonstrating a dependence on VGLUT2 to maintain normal levels of both histaminergic and nonhistaminergic itch. This study establishes that VGLUT2 is a major player in TRPV1 thermal nociception and also serves to regulate a normal itch response.
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Itch can be suppressed by painful stimuli, but the underlying neural basis is unknown. We generated conditional null mice in which vesicular glutamate transporter type 2 (VGLUT2)-dependent synaptic glutamate release from mainly Nav1.8-expressing nociceptors was abolished. These mice showed deficits in pain behaviors, including mechanical pain, heat pain, capsaicin-evoked pain, inflammatory pain, and neuropathic pain. ⋯ Consequently, coinjection of capsaicin was no longer able to mask itch evoked by pruritogenic compounds. Our studies suggest that synaptic glutamate release from a group of peripheral nociceptors is required to sense pain and suppress itch. Elimination of VGLUT2 in these nociceptors creates a mouse model of chronic neurogenic itch.