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.

Humans can read and comprehend text rapidly, implying that readers might process multiple words per fixation. However, the extent to which parafoveal words are previewed and integrated into the evolving sentence context remains disputed. We investigated parafoveal processing during natural reading by recording brain activity and eye movements using MEG and an eye tracker while participants silently read one-line sentences. The sentences contained an unpredictable target word that was either congruent or incongruent with the sentence context. To measure parafoveal processing, we flickered the target words at 60 Hz and measured the resulting brain responses (i.e. Rapid Invisible Frequency Tagging, RIFT) during fixations on the pre-target words. Our results revealed a significantly weaker tagging response for target words that were incongruent with the previous context compared to congruent ones, even within 100ms of fixating the word immediately preceding the target. This reduction in the RIFT response was also found to be predictive of individual reading speed. We conclude that semantic information is not only extracted from the parafovea but can also be integrated with the previous context before the word is fixated. This early and extensive parafoveal processing supports the rapid word processing required for natural reading. Our study suggests that theoretical frameworks of natural reading should incorporate the concept of deep parafoveal processing.