Keratinocytes Communicate with Sensory Neurons via Synaptic-like Contacts.

OBJECTIVE: Pain, temperature, and itch are conventionally thought to be exclusively transduced by the intraepidermal nerve endings. Although recent studies have shown that epidermal keratinocytes also participate in sensory transduction, the mechanism underlying keratinocyte communication with intraepidermal nerve endings remains poorly understood. We sought to demonstrate the synaptic character of the contacts between keratinocytes and sensory neurons and their involvement in sensory communication between keratinocytes and sensory neurons. METHODS: Contacts were explored by morphological, molecular, and functional approaches in cocultures of epidermal keratinocytes and sensory neurons. To interrogate whether structures observed in vitro were also present in the human epidermis, in situ correlative light electron microscopy was performed on human skin biopsies. RESULTS: Epidermal keratinocytes dialogue with sensory neurons through en passant synaptic-like contacts. These contacts have the ultrastructural features and molecular hallmarks of chemical synaptic-like contacts: narrow intercellular cleft, keratinocyte synaptic vesicles expressing synaptophysin and synaptotagmin 1, and sensory information transmitted from keratinocytes to sensory neurons through SNARE-mediated (syntaxin1) vesicle release. INTERPRETATION: By providing selective communication between keratinocytes and sensory neurons, synaptic-like contacts are the hubs of a 2-site receptor. The permanent epidermal turnover, implying a specific en passant structure and high plasticity, may have delayed their identification, thereby contributing to the long-held concept of nerve endings passing freely between keratinocytes. The discovery of keratinocyte-sensory neuron synaptic-like contacts may call for a reassessment of basic assumptions in cutaneous sensory perception and sheds new light on the pathophysiology of pain and itch as well as the physiology of touch. ANN NEUROL 2020;88:1205-1219.

Resistance to Brown Ring Disease in the Manila clam, Ruditapes philippinarum: a study of selected stocks showing a recovery process by shell repair.

European stocks of the Manila clam Ruditapes philippinarum are affected by the Brown Ring Disease (BRD), which is caused by Vibrio tapetis. BRD is characterized by an accumulation of a brown organic matrix on the inner face of the shell. Clams that recover from BRD develop a white mineralized layer covering the brown matrix. Stocks of clams that showed resistance to BRD development, as enhanced recovery, have been monitored since 2000. We have examined two selected stocks: a Low Susceptibility (LS) stock and a High Susceptibility stock (HS), over three generations. The LS stock showed less evidence of the BRD symptoms, and more evidence of total shell repair, both in the field and following experimental challenge with V. tapetis, indicating that some clams may be less vulnerable to a V. tapetis attack than others. The inner face of the valves of the LS and HS clams of the two last generations were analysed with scanning electron microscopy. Examination of shells from BRD-affected clams showed that during the repair process, calcium crystals were progressively laid down until the affected zone was entirely covered. By the end of the shell repair process, a final organic layer covered the calcium crystal mounds. This layer seemed essential in the recovery process. The results indicate that the shell repair capability of the clams is the principal mechanism implicated in the development of BRD resistance in the Manila clam stocks. However, this resistance did not increase with generation because the broodstock was maintained at a site where selection pressure was low, due to a low prevalence of V. tapetis.