Neuron
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Comparative Study
Cav2.3 channels are critical for oscillatory burst discharges in the reticular thalamus and absence epilepsy.
Neurons of the reticular thalamus (RT) display oscillatory burst discharges that are believed to be critical for thalamocortical network oscillations related to absence epilepsy. Ca²+-dependent mechanisms underlie such oscillatory discharges. However, involvement of high-voltage activated (HVA) Ca²+ channels in this process has been discounted. ⋯ Consequently, the lack of Ca(v)2.3 resulted in a marked decrease in the sensitivity of the animal to γ-butyrolactone-induced absence epilepsy. Local blockade of Ca(v)2.3 channels in the RT mimicked the results of Ca(v)2.3⁻/⁻ mice. These results provide strong evidence that Ca(v)2.3 channels are critical for oscillatory burst discharges in RT neurons and for the expression of absence epilepsy.
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Opiates are utilized routinely and effectively as a short-term analgesic treatment for a variety of acute pain conditions such as occur following trauma, and for patients with painful terminal diseases such as cancer. Because opiate analgesics are highly addictive substances, their use in the treatment of chronic nonmalignant pain remains controversial.
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Tinnitus is a common disorder characterized by ringing in the ear in the absence of sound. Converging evidence suggests that tinnitus pathophysiology involves damage to peripheral and/or central auditory pathways. However, whether auditory system dysfunction is sufficient to explain chronic tinnitus is unclear, especially in light of evidence implicating other networks, including the limbic system. ⋯ However, the nucleus accumbens exhibited the greatest degree of hyperactivity, specifically to sounds frequency-matched to patients' tinnitus. Complementary structural differences were identified in ventromedial prefrontal cortex, another limbic structure heavily connected to the nucleus accumbens. Furthermore, tinnitus-related anomalies were intercorrelated in the two limbic regions and between limbic and primary auditory areas, indicating the importance of auditory-limbic interactions in tinnitus.
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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.