Merkel Cells Activate Sensory Neural Pathways through Adrenergic Synapses

Area of Science:

• Neuroscience
• Cell Biology
• Dermatology

Background:

• Epithelial-neuronal signaling is crucial for sensory perception, including touch, itch, and pain.
• The precise mechanisms by which skin cells influence neuronal activity remain largely unknown.
• Merkel cells, a type of mechanosensory epidermal cell, are hypothesized to communicate with neurons via chemical synapses.

Purpose of the Study:

• To investigate the release mechanisms and neurotransmitter receptors involved in Merkel cell-neuronal communication.
• To test the hypothesis that Merkel cells activate neuronal afferents through chemical synaptic transmission.

Main Methods:

• RNA sequencing of adult mouse Merkel cells to identify expressed molecules.
• Live-cell imaging to visualize neurotransmitter release.
• Genetic manipulation to silence presynaptic vesicle release and delete neuronal receptors.

Main Results:

• Merkel cells express presynaptic molecules and machinery for adrenergic transmission.
• Activity- and VMAT-dependent release of catecholamine neurotransmitter analogs was observed.
• Inhibition of touch-evoked firing occurred with presynaptic silencing or neuronal beta-2 adrenergic receptor deletion.

Conclusions:

• Merkel cells utilize adrenergic transmission to excite mechanosensory afferents.
• Both presynaptic (SNARE-mediated release) and postsynaptic (beta-2 adrenergic receptors) mechanisms are identified.
• These findings elucidate how Merkel cells contribute to the encoding of gentle touch.