Abstract
How thermal, mechanical and chemical stimuli applied to the skin are transduced into signals transmitted by peripheral neurons to the CNS is an area of intense study. Several studies indicate that transduction mechanisms are intrinsic to cutaneous neurons and that epidermal keratinocytes only modulate this transduction. Using mice expressing channelrhodopsin (ChR2) in keratinocytes we show that blue light activation of the epidermis alone can produce action potentials (APs) in multiple types of cutaneous sensory neurons including SA1, A-HTMR, CM, CH, CMC, CMH and CMHC fiber types. In loss of function studies, yellow light stimulation of keratinocytes that express halorhodopsin reduced AP generation in response to naturalistic stimuli. These findings support the idea that intrinsic sensory transduction mechanisms in epidermal keratinocytes can directly elicit AP firing in nociceptive as well as tactile sensory afferents and suggest a significantly expanded role for the epidermis in sensory processing.
Highlights
Cutaneous primary sensory afferents are the first in a chain of neurons that convert environmental stimuli into recognizable sensations of touch, heat, cold and pain
Similar to Daou et al (Daou et al, 2013), we found that light stimulation of the skin and activation of ChR2 in sensory afferents elicits robust nocifensive behaviors in mice
No significant differences in these values were observed between genotypes
Summary
Cutaneous primary sensory afferents are the first in a chain of neurons that convert environmental stimuli into recognizable sensations of touch, heat, cold and pain. It has been proposed that non-neuronal cells of the skin, keratinocytes, contribute to the initial transduction process through regulated release of neuroactive substances (Zhao et al, 2008; Dussor et al, 2009; Mandadi et al, 2009; Hou et al, 2011; Barr et al, 2013) Testing this in an intact system has been difficult because the complexity in skin-nerve interactions prohibits isolation of the skin and neuronal output (a behavioral reflex or the pattern of axonal firing) since any natural stimulation (e.g., mechanical or thermal) simultaneously affects both keratinocytes and sensory neurons. For mice that only express ChR2 in skin keratinocytes, light stimulation was sufficient to generate nocifensive behaviors and regulate firing properties and evoke APs in specific subsets of cutaneous afferents, several which are known to activate in response to painful stimuli. These data indicate that Merkel cells are not unique in their ability to directly generate action potentials in sensory neurons and that light-mediated activation of keratinocytes is sufficient to engage an endogenous mechanism that can directly regulate cutaneous afferent firing
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