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The cellular and molecular basis of vertebrate touch reception remains least understood among the traditional five senses. Somatosensory afferents that innervate the skin encode distinct tactile qualities, such as flutter, slip, and pressure. Gentle touch is thought to be transduced by somatosensory afferents whose tactile end organs selectively filter mechanical stimuli. These tactile end organs comprise afferent terminals in association with non-neuronal cell types such as Merkel cells, keratinocytes, and Schwann cells. An open question is whether these non-neuronal cells serve primarily as passive mechanical filters or whether they actively participate in mechanosensory transduction. This question has been most extensively studied in Merkel cells, which are epidermal cells that complex with sensory afferents in regions of high tactile acuity such as fingertips, whisker follicles, and touch domes. Merkel cell-neurite complexes mediate slowly adapting type I (SAI) responses, which encode sustained pressure and represent object features with high fidelity. How Merkel cells contribute to unique SAI firing patterns has been debated for decades; however, three recent studies in rodent models provide some direct answers. First, whole-cell recordings demonstrate that Merkel cells are touch-sensitive cells with fast, mechanically activated currents that require Piezo2 . Second, optogenetics and intact recordings show that Merkel cells mediate sustained SAI firing. Finally, loss-of-function studies in transgenic mouse models reveal that SAI afferents are also touch sensitive. Together, these studies identify molecular mechanisms of mechanotransduction in Merkel cells, reveal unexpected functions for these cells in touch, and support a revised, two-receptor site model of mechanosensory transduction.

Chemical peeling is usually performed by dermatologists, plastic surgeons, and aestheticians for the treatment of photo-aged skin, dyspigmented skin, skin prone to acne eruption, and pre-cancerous skin lesions, etc. In this research paper, we report our investigative findings to understand the mode of action of a commercial professional chemical peel to treat hyperpigmented and photoaged skin. In the in-vitro experiments, we found that the peel inhibits enzymes that are responsible for degradation of collagen and elastin, and the production of melanin pigment. It was surprising to observe that trichloroacetic acid (TCA), which is considered a workhorse of chemical peels for its cauterant action, could synergistically promote the inhibitory action of lactic acid. The rationale behind this synergistic effect could be the conformational change in TCA from linear structure to ring-like structure, which was elucidated through sequential docking using Rosetta software. The in-vitro results on collagen and elastin were corroborated by up-regulation of COL1A, COL3B, fibronectin, and elastin gene expression from 3D human skin equivalents treated with the peel. The findings were further validated through ex-vivo testing on human skin biopsy. The peel significantly inhibits the production of total melanin, and ameliorates photo-damage that was evident through repair of the collagen in the skin exposed to a biological effective dose of UV daily light (6 J/cm 2 ). These research findings have implications for product developers and users (dermatologists, plastic surgeons, and aestheticians) in improving safety and efficacy of chemical peels/peeling.

The cellular basis of touch has long been debated, in particular the relationship between sensory neurons and non-neuronal cells; a mouse study uses optogenetics to identify their distinct and collaborative roles, with skin-derived Merkel cells both transducing touch and actively tuning responses of touch-sensitive neurons. Non-neural Merkel cells stay in touch Merkel cells (also known as Merkel-Ranvier cells) are found in the vertebrate epidermis. They are non-neuronal but may make 'synapse-like' contact with neighbouring cells. It has been suggested that they are associated with the sensation of touch, but this has been difficult to prove and remains controversial. In this week's Nature two teams present clear evidence that Merkel cells are autonomous mechanosensors essential to fine touch perception. The cells express the mechanosensitive channel Piezo2, which allows them to actively tune somatosensory neurons' responses to touch. These results are consistent with a compound receptor system model in which epidermal cells help neurons to discriminate between different types of touch — such as flutter, stretch and pressure — and therefore to decode the fine details of objects. Touch submodalities, such as flutter and pressure, are mediated by somatosensory afferents whose terminal specializations extract tactile features and encode them as action potential trains with unique activity patterns 1 . Whether non-neuronal cells tune touch receptors through active or passive mechanisms is debated. Terminal specializations are thought to function as passive mechanical filters analogous to the cochlea’s basilar membrane, which deconstructs complex sounds into tones that are transduced by mechanosensory hair cells. The model that cutaneous specializations are merely passive has been recently challenged because epidermal cells express sensory ion channels and neurotransmitters 2 , 3 ; however, direct evidence that epidermal cells excite tactile afferents is lacking. Epidermal Merkel cells display features of sensory receptor cells 4 , 5 and make ‘synapse-like’ contacts 5 , 6 with slowly adapting type I (SAI) afferents 7 , 8 , 9 . These complexes, which encode spatial features such as edges and texture 1 , localize to skin regions with high tactile acuity, including whisker follicles, fingertips and touch domes. Here we show that Merkel cells actively participate in touch reception in mice. Merkel cells display fast, touch-evoked mechanotransduction currents. Optogenetic approaches in intact skin show that Merkel cells are both necessary and sufficient for sustained action-potential firing in tactile afferents. Recordings from touch-dome afferents lacking Merkel cells demonstrate that Merkel cells confer high-frequency responses to dynamic stimuli and enable sustained firing. These data are the first, to our knowledge, to directly demonstrate a functional, excitatory connection between epidermal cells and sensory neurons. Together, these findings indicate that Merkel cells actively tune mechanosensory responses to facilitate high spatio-temporal acuity. Moreover, our results indicate a division of labour in the Merkel cell–neurite complex: Merkel cells signal static stimuli, such as pressure, whereas sensory afferents transduce dynamic stimuli, such as moving gratings. Thus, the Merkel cell–neurite complex is an unique sensory structure composed of two different receptor cell types specialized for distinct elements of discriminative touch.

The cellular basis of touch has long been debated, in particular the relationship between sensory neurons and non-neuronal cells; a mouse study uses optogenetics to identify their distinct and collaborative roles, with skin-derived Merkel cells both transducing touch and actively tuning responses of touch-sensitive neurons.

The majority of investigated eyes describe specific variations of known eye types. But the eyes of two different insects, the compound-lens eyes of Strepsiptera and the scanning eyes of dytiscid diving beetle larvae, do not follow known design principles. Most adult insects possess a pair of large compound eyes, often occupying significant portion of their head. Compound eyes are typically composed of hundreds to thousands of ommatidia, each containing 8-10 photoreceptors. For the most part the receptors within each ommatidium act as a single sampling unit, averaging light intensities within all of them. Males of the insect order Strepsiptera are different: their eyes are composed of a smaller number of relatively large units (eyelets), each with an extended retina with often more than one hundred photoreceptors. In the strepsipteran species, Xenos peckii, each eye has about 50 eyelets. By using a behavioral paradigm based on the optomotor response, I have provided evidence that the eyelets in Xenos peckii eyes are image forming units. Each eyelet could sample up to 13 points, as opposed to one sampling point in an ommatidium. This unusual design has already inspired engineers to apply it into artificial optical solutions, such as a compact infra-red camera. Like strepsipteran eyes, the principal eyes of the Sunburst Diving Beetle (Thermonectus marmoratus) larvae are among the most bizarre in the animal kingdom. There are three different larval instars, all of which bear six eyes (stemmata) on each side of their head. The two frontal pairs, known as the principal eyes, are used to scan potential prey prior to capture. The principal eyes form long tubes, have bifocal lenses and are characterized by at least two one-dimensional retinas at their ends: a deep distal retina closer to the lens, and a proximal retina that lies directly underneath. The distal retina expresses long-wavelength opsin (TmLW) mRNA, whereas the proximal retina expresses ultraviolet opsin (TmUV II) mRNA. In contrast to third instars, the proximal retina of first instars shows a weak expression of the TmUV I mRNA limited only to its dorsal half. Third instars lack expression of TmUV I mRNA in their proximal retina. By using intracellular recordings from photoreceptor cells in third instars, I have shown that the distal retina has maximum sensitivity in green (LW), approximately 520-540 nm with an addition of a smaller peak in ultra-violet (UV), around 340-360 nm. The proximal retina is UV-sensitive with peak absorbance at 374 nm. This arrangement, to my knowledge, is the first example of a tiered system with the LW-sensitive cells distal to the UV-sensitive cells. Perhaps this unusual spectral arrangement creates a novel contrast enhancement mechanism. It is still unknown if these animals are capable of color and polarization sensitivity, and both of these visual modalities, including monochromatic vision, can be affected by the strange placement of the distal and proximal retina. Additional optical, physiological and behavioral studies will be necessary to answer these questions.

General anesthetics are neurotoxic to the developing rodent and primate brains leading to neurocognitive and socio-affective impairment later in life. In addition, sleep patterns are important predictors of cognitive outcomes. Yet, little is known about how anesthetics affect sleep-wake behaviors and their corresponding oscillations. Here we examine how neonatal general anesthesia affects sleep and wake behavior and associated neuronal oscillations. We exposed male and female rat pups to either 6 h of continuous isoflurane or sham anesthesia (compressed air) at the peak of their brain development (postnatal day 7). One cohort of animals was used to examine neurotoxic insult 2 h post-anesthesia exposure. At weaning age, a second cohort of rats was implanted with cortical electroencephalogram electrodes and allowed to recover. During adolescence, we measured sleep architecture (divided into wake, non-rapid eye movement, and rapid eye movement sleep) and electroencephalogram power spectra over a 24 h period. We found that exposure to neonatal isoflurane caused extensive neurotoxicity but did not disrupt sleep architecture in adolescent rats. However, these animals had a small but significant reduction in beta oscillations, specifically in the 12–20 Hz beta 1 range, associated with wake behavior. Furthermore, beta oscillations play a critical role in cortical development, cognitive processing, and homeostatic sleep drive. We speculate that dysregulation of beta oscillations may be implicated in cognitive and socio-affective outcomes associated with neonatal anesthesia.