Congratulations to June 2019 JBC SMART Brain Prize Winner

June 26, 2019

Congratulations to Robert H. Goldstein  for winning the June 2019 JBC SMART Brain Prize for the outstanding article: “Location and Plasticity of the Sodium Spike Initiation Zone in Nociceptive Terminals In Vivo”, published in Neuron in April 2019.

Robert is a 5troberth year PhD candidate in Neurobiology in Prof. Binshtok Alex from the department of Medical Neurobiology. Robert is researching mechanisms of transduction, action potential initiation and plasticity, at the free nerve endings of nociceptors. He implements advanced imaging techniques, while recording noxious stimuli induced neuronal signals in peripheral nociceptive nerve terminals innervating the mouse cornea, in vivo and in vitro. Furthermore, these studies are accompanied with neuronal computational models for validation and behavioral assays for preclinical pathological significance.

Our sensation of pain begins with the neuronal response of specialized sensory nerve terminals to noxious stimuli. Although this is a well understood process, it is puzzling why one experiences the same stimulus as moderate or intense pain, depending on context. In our paper we describe the previously unknown location of action potential generation in nociceptor terminals. Furthermore, we found that change in the site of action potential initiation during inflammatory conditions, can encode how pain is experienced. Providing an explanation to why pain sensitivity can increase, such that even a light touch near a sore can produce severe pain.


Figure 6. Scheme Depicting Capsaicin-Induced Signal Generation in Nociceptive Terminals and Fibers. Left: in normal conditions, application of capsaicin on the nociceptive terminal tip evokes activation of terminal TRPV1 channels, leading to Ca2+ entry and depolarization. The depolarization activates VGCCs, thus adding to capsaicin-induced Ca2+ signals. The Ca2+ signal and capsaicin-induced depolarization propagate along the terminal in a Nav-independent manner for ∼25 μm. This depolarization reaches a Nav-SIZ, the location of available Navs, where activation of Navs generates propagating action potentials, which propagate toward the CNS. Right: acute inflammation or application of proinflammatory mediators, presumably by virtue of their relieving effect on Nav slow inactivation, “shifts” the location of available Navs toward the terminal, enhancing the response to capsaicin, thus rendering the nociceptive terminal branch hyperactive.

The upcoming deadline for the next SMART Brain Prize is October 31, 2019
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